Details
Stereochemistry | ACHIRAL |
Molecular Formula | C30H29ClN6O3 |
Molecular Weight | 557.043 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCOC1=CC2=C(C=C1NC(=O)\C=C\CN(C)C)C(NC3=CC(Cl)=C(OCC4=CC=CC=N4)C=C3)=C(C=N2)C#N
InChI
InChIKey=JWNPDZNEKVCWMY-VQHVLOKHSA-N
InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
Molecular Formula | C30H29ClN6O3 |
Molecular Weight | 557.043 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: http://adisinsight.springer.com/drugs/800021154Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26089701 | https://www.ncbi.nlm.nih.gov/pubmed/15715478
Sources: http://adisinsight.springer.com/drugs/800021154
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26089701 | https://www.ncbi.nlm.nih.gov/pubmed/15715478
Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.
Originator
Sources: http://adisinsight.springer.com/drugs/800021154
Curator's Comment: # Wyeth (now Pfizer)
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15715478 |
59.0 nM [IC50] | ||
Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15715478 |
92.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NERLYNX Approved UseNERLYNX is indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy. Launch Date2017 |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
71.8 ng/mL |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
73.1 ng/mL |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
76.3 ng/mL |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
81.5 ng/mL |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
891 ng × h/mL |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
1060 ng × h/mL |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
1640 ng × h/mL |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
1110 ng × h/mL |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12.6 h |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
14.6 h |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
14.3 h |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
22.7 h |
240 mg 1 times / day steady-state, oral dose: 240 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
NERATINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
NERATINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg 1 times / day steady, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: |
unhealthy, 49.5 years (range: 42-63 years) Health Status: unhealthy Age Group: 49.5 years (range: 42-63 years) Sex: M+F Sources: |
DLT: Diarrhea... Disc. AE: Fatigue... Dose limiting toxicities: Diarrhea (grade 3, 3 patients) AEs leading todiscontinuation/dose reduction: Fatigue (all grades, 5 patients) Sources: |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
DLT: Diarrhea, Diarrhea... Dose limiting toxicities: Diarrhea (all grades, 95%) Sources: Diarrhea (grade 3, 40%) Diarrhea (grade 4, 0.1%) |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Disc. AE: Nausea, Abdominal pain... Other AEs: Nausea, Abdominal pain... AEs leading to discontinuation/dose reduction: Nausea (grade 3, 2%) Other AEs:Abdominal pain (grade 3, 2%) Abdominal pain upper (grade 3, 2%) Abdominal pain lower (grade 3, 2%) Vomiting (grade 3, 3%) Fatigue (grade 3, 2%) Alanine aminotransferase increased (grade 3, 1%) Alanine aminotransferase increased (grade 4, 0.2%) Nausea (all grades, 43%) Sources: Abdominal pain (all grades, 36%) Abdominal pain upper (all grades, 36%) Abdominal pain lower (all grades, 36%) Vomiting (all grades, 26%) Stomatitis (all grades, 14%) Aphthous stomatitis (all grades, 14%) Mouth ulceration (all grades, 14%) Oral mucosal blistering (all grades, 14%) Mucosal inflammation (all grades, 14%) Oropharyngeal pain (all grades, 14%) Oral pain (all grades, 14%) Glossodynia (all grades, 14%) Glossitis (all grades, 14%) Cheilitis (all grades, 14%) Stomatitis (grade 3, 0.3%) Aphthous stomatitis (grade 3, 0.3%) Mouth ulceration (grade 3, 0.3%) Oral mucosal blistering (grade 3, 0.3%) Mucosal inflammation (grade 3, 0.3%) Oropharyngeal pain (grade 3, 0.3%) Oral pain (grade 3, 0.3%) Glossodynia (grade 3, 0.3%) Glossitis (grade 3, 0.3%) Cheilitis (grade 3, 0.3%) Dyspepsia (all grades, 10%) Dyspepsia (grade 3, 0.4%) Abdominal distension (all grades, 5%) Abdominal distension (grade 3, 0.3%) Dry mouth (all grades, 3%) Dry mouth (grade 3, 0.1%) Fatigue (all grades, 27%) Alanine aminotransferase increased (all grades, 9%) Aspartate aminotransferase increased (all grades, 7%) Aspartate aminotransferase increased (grade 3, 0.5%) Aspartate aminotransferase increased (grade 4, 0.2%) Urinary tract infection (all grades, 5%) Urinary tract infection (grade 3, 0.1%) Weight decreased (all grades, 5%) Weight decreased (grade 3, 0.1%) Decreased appetite (all grades, 12%) Decreased appetite (grade 3, 0.2%) Dehydration (all grades, 4%) Dehydration (grade 3, 0.9%) Dehydration (grade 4, 0.1%) Muscle spasms (all grades, 11%) Muscle spasms (grade 3, 0.1%) Epistaxis (all grades, 5%) Rash (all grades, 18%) Rash erythematous (all grades, 18%) Rash follicular (all grades, 18%) Generalized rash (all grades, 18%) Rash pruritic (all grades, 18%) Rash pustular (all grades, 18%) Maculopapular rash (all grades, 18%) Rash papular (all grades, 18%) Dermatitis (all grades, 18%) Dermatitis acneiform (all grades, 18%) Toxic skin eruption (all grades, 18%) Rash (grade 3, 0.6%) Rash erythematous (grade 3, 0.6%) Rash follicular (grade 3, 0.6%) Generalized rash (grade 3, 0.6%) Rash pruritic (grade 3, 0.6%) Rash pustular (grade 3, 0.6%) Maculopapular rash (grade 3, 0.6%) Rash papular (grade 3, 0.6%) Dermatitis (grade 3, 0.6%) Dermatitis acneiform (grade 3, 0.6%) Toxic skin eruption (grade 3, 0.6%) Dry skin (all grades, 6%) Nail disorder (all grades, 8%) Paronychia (all grades, 8%) Onychoclasis (all grades, 8%) Nail discoloration (all grades, 8%) Nail toxicity (all grades, 8%) Nail growth abnormal (all grades, 8%) Nail dystrophy (all grades, 8%) Nail disorder (grade 3, 0.3%) Paronychia (grade 3, 0.3%) Onychoclasis (grade 3, 0.3%) Nail discoloration (grade 3, 0.3%) Nail toxicity (grade 3, 0.3%) Nail growth abnormal (grade 3, 0.3%) Nail dystrophy (grade 3, 0.3%) Skin fissures (all grades, 2%) Skin fissures (grade 3, 0.1%) |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Other AEs: Bilirubin increased, Bilirubin increased... Other AEs: Bilirubin increased (all grades, 11.1%) Sources: Bilirubin increased (grade 3, 0.1%) Alkaline phosphatase (all grades, 22.7%) Creatinine increased (all grades, 12.5%) Creatinine increased (grade 4, 0.1%) Creatinine increased (grade 3, 0.1%) Hypercalcemia (all grades, 11.2%) Hypercalcemia (grade 4, 0.2%) Hypercalcemia (grade 3, 0.4%) Hypermagnesemia (all grades, 5.2%) Hypermagnesemia (grade 4, 0.1%) Hypermagnesemia (grade 3, 0.9%) Hypernatremia (all grades, 10.3%) Hypernatremia (grade 4, 0.1%) Hypernatremia (grade 3, 0.1%) Hypoalbuminemia (all grades, 8.4%) Hypoalbuminemia (grade 3, 0.1%) Hypocalcemia (all grades, 48.9%) Hypocalcemia (grade 4, 0.9%) Hypocalcemia (grade 3, 0.1%) Hypokalemia (all grades, 7.5%) Hypokalemia (grade 4, 0.1%) Hypokalemia (grade 3, 0.3%) Hypomagnesemia (all grades, 7.2%) Hypomagnesemia (grade 4, 0.2%) Hypomagnesemia (grade 3, 0.4%) Hyponatremia (all grades, 11.6%) Hyponatremia (grade 3, 0.9%) |
180 mg 1 times / day steady, oral Dose: 180 mg, 1 times / day Route: oral Route: steady Dose: 180 mg, 1 times / day Sources: |
unhealthy, 56.5 years (range: 46-90 years) Health Status: unhealthy Age Group: 56.5 years (range: 46-90 years) Sex: F Sources: |
DLT: Diarrhea... Disc. AE: Fatigue... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) AEs leading todiscontinuation/dose reduction: Fatigue (all grades, 1 patient) Sources: |
320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Disc. AE: Diarrhea, Fatigue... Other AEs: Abdominal pain, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (all grades, 92%) Other AEs:Fatigue (all grades, 49%) Abdominal pain (all grades, 21%) Sources: Nausea (all grades, 54%) Vomiting (all grades, 49%) Anorexia (all grades, 33%) Rash (all grades, 8%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Fatigue | all grades, 5 patients Disc. AE |
400 mg 1 times / day steady, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: |
unhealthy, 49.5 years (range: 42-63 years) Health Status: unhealthy Age Group: 49.5 years (range: 42-63 years) Sex: M+F Sources: |
Diarrhea | grade 3, 3 patients DLT, Disc. AE |
400 mg 1 times / day steady, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: |
unhealthy, 49.5 years (range: 42-63 years) Health Status: unhealthy Age Group: 49.5 years (range: 42-63 years) Sex: M+F Sources: |
Diarrhea | all grades, 95% DLT, Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Diarrhea | grade 3, 40% DLT, Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Diarrhea | grade 4, 0.1% DLT, Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dyspepsia | all grades, 10% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Muscle spasms | all grades, 11% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Decreased appetite | all grades, 12% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Aphthous stomatitis | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Cheilitis | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Glossitis | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Glossodynia | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Mouth ulceration | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Mucosal inflammation | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oral mucosal blistering | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oral pain | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oropharyngeal pain | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Stomatitis | all grades, 14% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dermatitis acneiform | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dermatitis | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Generalized rash | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Maculopapular rash | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash erythematous | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash follicular | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash papular | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash pruritic | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash pustular | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Toxic skin eruption | all grades, 18% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Skin fissures | all grades, 2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Vomiting | all grades, 26% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Fatigue | all grades, 27% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dry mouth | all grades, 3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain lower | all grades, 36% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain upper | all grades, 36% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain | all grades, 36% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dehydration | all grades, 4% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nausea | all grades, 43% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal distension | all grades, 5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Epistaxis | all grades, 5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Urinary tract infection | all grades, 5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Weight decreased | all grades, 5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dry skin | all grades, 6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Aspartate aminotransferase increased | all grades, 7% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail discoloration | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail disorder | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail dystrophy | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail growth abnormal | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail toxicity | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Onychoclasis | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Paronychia | all grades, 8% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Alanine aminotransferase increased | all grades, 9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dry mouth | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Muscle spasms | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Skin fissures | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Urinary tract infection | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Weight decreased | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Decreased appetite | grade 3, 0.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal distension | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Aphthous stomatitis | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Cheilitis | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Glossitis | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Glossodynia | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Mouth ulceration | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Mucosal inflammation | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail discoloration | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail disorder | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail dystrophy | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail growth abnormal | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nail toxicity | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Onychoclasis | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oral mucosal blistering | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oral pain | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Oropharyngeal pain | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Paronychia | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Stomatitis | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dyspepsia | grade 3, 0.4% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Aspartate aminotransferase increased | grade 3, 0.5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dermatitis acneiform | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dermatitis | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Generalized rash | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Maculopapular rash | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash erythematous | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash follicular | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash papular | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash pruritic | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash pustular | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Rash | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Toxic skin eruption | grade 3, 0.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dehydration | grade 3, 0.9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Alanine aminotransferase increased | grade 3, 1% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain lower | grade 3, 2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain upper | grade 3, 2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Abdominal pain | grade 3, 2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Fatigue | grade 3, 2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Nausea | grade 3, 2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Vomiting | grade 3, 3% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Dehydration | grade 4, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Aspartate aminotransferase increased | grade 4, 0.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Alanine aminotransferase increased | grade 4, 0.2% Disc. AE |
240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypernatremia | all grades, 10.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Bilirubin increased | all grades, 11.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypercalcemia | all grades, 11.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hyponatremia | all grades, 11.6% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Creatinine increased | all grades, 12.5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Alkaline phosphatase | all grades, 22.7% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypocalcemia | all grades, 48.9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypermagnesemia | all grades, 5.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypomagnesemia | all grades, 7.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypokalemia | all grades, 7.5% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypoalbuminemia | all grades, 8.4% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Bilirubin increased | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Creatinine increased | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypernatremia | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypoalbuminemia | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypocalcemia | grade 3, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypokalemia | grade 3, 0.3% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypercalcemia | grade 3, 0.4% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypomagnesemia | grade 3, 0.4% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypermagnesemia | grade 3, 0.9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hyponatremia | grade 3, 0.9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Creatinine increased | grade 4, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypermagnesemia | grade 4, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypernatremia | grade 4, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypokalemia | grade 4, 0.1% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypercalcemia | grade 4, 0.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypomagnesemia | grade 4, 0.2% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Hypocalcemia | grade 4, 0.9% | 240 mg 1 times / day steady, oral Recommended Dose: 240 mg, 1 times / day Route: oral Route: steady Dose: 240 mg, 1 times / day Sources: |
unhealthy, 52 years Health Status: unhealthy Age Group: 52 years Sex: F Sources: |
Fatigue | all grades, 1 patient Disc. AE |
180 mg 1 times / day steady, oral Dose: 180 mg, 1 times / day Route: oral Route: steady Dose: 180 mg, 1 times / day Sources: |
unhealthy, 56.5 years (range: 46-90 years) Health Status: unhealthy Age Group: 56.5 years (range: 46-90 years) Sex: F Sources: |
Diarrhea | grade 3, 1 patient DLT, Disc. AE |
180 mg 1 times / day steady, oral Dose: 180 mg, 1 times / day Route: oral Route: steady Dose: 180 mg, 1 times / day Sources: |
unhealthy, 56.5 years (range: 46-90 years) Health Status: unhealthy Age Group: 56.5 years (range: 46-90 years) Sex: F Sources: |
Abdominal pain | all grades, 21% | 320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Anorexia | all grades, 33% | 320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Vomiting | all grades, 49% | 320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Fatigue | all grades, 49% Disc. AE |
320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Nausea | all grades, 54% | 320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Rash | all grades, 8% | 320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Diarrhea | all grades, 92% Disc. AE |
320 mg 1 times / day steady, oral MTD Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy, 57 years (range: 34-80 years) Health Status: unhealthy Age Group: 57 years (range: 34-80 years) Sex: M+F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [IC50 1 uM] | yes (co-administration study) Comment: NERATINIB increases digoxin Cmax& AUC Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=67 Page: - |
|||
yes [Inhibition 10 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: ketoconazole increased Cmax and AUC by 3.2- and 4.8-fold respectively, rifampin (a strong CYP3A4 inducer) decreased the Cmax and AUC of neratinib by 76% and 87%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208051Orig1s000MultidisciplineR.pdf#page=65 Page: - |
|||
minor | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sample Use Guides
Patients who received 40, 80, or 120 mg experienced no dose-limiting toxicities. The study determined the maximum tolerated dose at 320 mg, with 240 mg being the therapeutic dose.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26260909
both very low (10 nM) and physiologically attainable concentrations of neratinib (133 nM) significantly inhibited the autophosphorylation of HER2/neu and activation of S6 in primary carcinosarcoma cells
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:27:29 GMT 2025
by
admin
on
Mon Mar 31 18:27:29 GMT 2025
|
Record UNII |
JJH94R3PWB
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
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Preferred Name | English | ||
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Official Name | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Systematic Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C1967
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
|
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|
FDA ORPHAN DRUG |
699119
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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NCI_THESAURUS |
C129825
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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WHO-ATC |
L01XE45
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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|
NDF-RT |
N0000175605
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
NERATINIB
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
|
PRIMARY | |||
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CHEMBL180022
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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PRIMARY | |||
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9915743
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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PRIMARY | |||
|
5252
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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PRIMARY | |||
|
61397
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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SUB32232
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admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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DTXSID70220132
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DB11828
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admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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8878
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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JJH94R3PWB
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admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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1940643
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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698387-09-6
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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C49094
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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m7827
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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PRIMARY | Merck Index | ||
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JJH94R3PWB
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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SS-120
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876310-02-0
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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NON-SPECIFIC STEREOCHEMISTRY | |||
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100000124443
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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Neratanib
Created by
admin on Mon Mar 31 18:27:29 GMT 2025 , Edited by admin on Mon Mar 31 18:27:29 GMT 2025
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Related Record | Type | Details | ||
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OFF-TARGET->INHIBITOR |
INHIBITOR
Percent inhibition of specific binding
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SALT/SOLVATE -> PARENT |
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CELL->INHIBITOR |
CELL PROLIFERATION
IC50
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SALT/SOLVATE -> PARENT |
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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TARGET -> INHIBITOR |
IC50
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METABOLIC ENZYME -> SUBSTRATE |
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TARGET -> INHIBITOR |
Radioligand binding assay
BINDING
IC50
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BINDER->LIGAND |
ex vivo protein binding of neratinib in human plasma samples from clinical study in healthy subjects as determined using ult racentrifugation was 88%
BINDING
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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OFF-TARGET->INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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TRANSPORTER -> SUBSTRATE |
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TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
IC50
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OFF-TARGET->INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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CUMULATIVE EXCRETION |
URINE
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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TARGET -> INHIBITOR |
Neratinib concentration at 10 microM
Percent inhibition of specific binding
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TARGET -> INHIBITOR |
± 4.37
IRREVERSIBLE INHIBITOR
IC50
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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TARGET -> INHIBITOR |
Cyclin D1 expression in BT474 cells
INHIBITOR
IC50
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CELL->INHIBITOR |
CELL PROLIFERATION
IC50
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
HER2 ligand-independent receptor phosphorylation in BT474
IRREVERSIBLE INHIBITOR
IC50
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TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
IC50
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TARGET -> INHIBITOR |
IC50
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OFF-TARGET->INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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TARGET -> INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
EGFR-dependent receptor phosphorylation in A431 cells
IC50
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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METABOLIC ENZYME -> NON-INDUCER |
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TRANSPORTER -> INHIBITOR |
IC50
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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OFF-TARGET->INHIBITOR |
Radioligand binding assay
BINDING
IC50
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OFF-TARGET->INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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TARGET -> INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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METABOLIC ENZYME -> NON-INHIBITOR |
IC50
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CELL->INHIBITOR |
CELL PROLIFERATION
IC50
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TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
IC50
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TARGET -> INHIBITOR |
IC50
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CUMULATIVE EXCRETION |
FECAL
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BINDER->LIGAND |
In vitro, neratinib was highly bound (N 99 %) to human plasma proteins at clinical exposures. click to edit
BINDING
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TARGET -> INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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TRANSPORTER -> INHIBITOR |
Neratinib concentration at 10 microM
INHIBITOR
Percent inhibition of specific binding
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TARGET -> INHIBITOR |
Radioligand binding assay
BINDING
IC50
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Related Record | Type | Details | ||
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METABOLITE LESS ACTIVE -> PARENT |
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
Inhibition of HER2 kinase activity (in autophosphorylation assay; Neratinib IC50 = 39 nM)
INHIBITOR
IC50
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METABOLITE LESS ACTIVE -> PARENT |
IC50 for HER2 kinase activity was up to 19 fold higher when compared to neratinib.
INHIBITOR
IC50
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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Dose PHARMACOKINETIC PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Route of Administration PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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Dose PHARMACOKINETIC PHARMACOKINETIC |
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Cmax | PHARMACOKINETIC |
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Dose PHARMACOKINETIC PHARMACOKINETIC |
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