Details
Stereochemistry | ACHIRAL |
Molecular Formula | C26H26F3N3O3 |
Molecular Weight | 485.4981 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H]1CN(C[C@@H](C)O1)C2=NC=C(NC(=O)C3=C(C)C(=CC=C3)C4=CC=C(OC(F)(F)F)C=C4)C=C2
InChI
InChIKey=VZZJRYRQSPEMTK-CALCHBBNSA-N
InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+
Molecular Formula | C26H26F3N3O3 |
Molecular Weight | 485.4981 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.drugbank.ca/drugs/DB09143
Curator's Comment: Description was created based on several sources, including
https://www.drugbank.ca/drugs/DB09143
Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.
Originator
Sources: http://adisinsight.springer.com/drugs/800029270
Curator's Comment: # Novartis
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL5971 Sources: https://www.drugbank.ca/drugs/DB09143 |
2.5 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ODOMZO Approved UseODOMZO is a hedgehog pathway inhibitor indicated for the treatment of
adult patients with locally advanced basal cell carcinoma (BCC) that has
recurred following surgery or radiation therapy, or those who are not
candidates for surgery or radiation therapy. Launch Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1030 ng/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SONIDEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
22 μg × h/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SONIDEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
28 day |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SONIDEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
SONIDEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
1% |
SONIDEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
3000 mg 1 times / day multiple, oral Highest studied dose Dose: 3000 mg, 1 times / day Route: oral Route: multiple Dose: 3000 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Other AEs: Creatine kinase increased, Rhabdomyolysis... Other AEs: Creatine kinase increased (grade 3-4, 1 patient) Sources: Rhabdomyolysis (3 patients) |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
DLT: Creatine kinase increased... Disc. AE: Muscle spasms, Alopecia... Dose limiting toxicities: Creatine kinase increased (2%) AEs leading todiscontinuation/dose reduction: Muscle spasms (9%) Sources: Alopecia (6%) Dysgeusia (5%) Weight decreased (5%) Fatigue (2%) Asthenia (1%) Nausea (4%) Decreased appetite (5%) Arthralgia (1%) Dysphagia (1%) General physical health deterioration (1%) Ageusia (2%) Dehydration (2%) |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Anemia, Constipation... AEs leading to discontinuation/dose reduction: Anemia (1%) Sources: Constipation (1%) Hypertension (1%) Hypogeusia (1%) |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Diarrhea, Gastroenteritis viral... AEs leading to discontinuation/dose reduction: Diarrhea (5%) Sources: Gastroenteritis viral (1%) Rhabdomyolysis (1%) Alanine aminotransferase increased (2%) Aspartate aminotransferase increased (2%) Dizziness (1%) Myalgia (3%) Muscular weakness (1%) Blood uric acid increased (1%) Vomiting (7%) Dyspnea (1%) Myoglobin blood increased (1%) Hypogeusia (1%) Amylase increased (1%) Malaise (1%) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Disc. AE: Alanine aminotransferase increased, Aspartate aminotransferase increased... AEs leading to discontinuation/dose reduction: Alanine aminotransferase increased (grade 3-4, 4%) Sources: Aspartate aminotransferase increased (all grades, 19%) Asthenia (4%) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Disc. AE: Amylase increased... AEs leading to discontinuation/dose reduction: Amylase increased (grade 3-4, 1%) Sources: |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Muscle spasms, Myalgia... Other AEs: Muscle spasms, Musculoskeletal pain... AEs leading to discontinuation/dose reduction: Muscle spasms (grade 3, 3%) Other AEs:Myalgia (all grades, 19%) Alopecia (all grades, 53%) Diarrhea (grade 3, 1%) Weight decreased (grade 3, 3%) Decreased appetite (grade 3, 1%) Muscle spasms (all grades, 54%) Sources: Musculoskeletal pain (all grades, 32%) Musculoskeletal pain (grade 3, 1%) Pruritus (all grades, 10%) Headache (all grades, 15%) Headache (grade 3, 1%) Fatigue (all grades, 41%) Pain (all grades, 14%) Pain (grade 3, 1%) Nausea (all grades, 39%) Diarrhea (all grades, 32%) Abdominal pain (all grades, 18%) Vomiting (all grades, 11%) Weight decreased (all grades, 30%) Decreased appetite (all grades, 23%) Increased serum creatinine (all grades, 92%) Creatine kinase increased (all grades, 61%) Hyperglycemia (all grades, 51%) Hyperglycemia (grade 3-4, 4%) Lipase increased (all grades, 43%) Alanine aminotransferase increased (all grades, 19%) Aspartate aminotransferase increased (grade 3-4, 4%) Amylase increased (all grades, 16%) Anemia (all grades, 32%) Lymphopenia (all grades, 28%) Lymphopenia (grade 3-4, 3%) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Disc. AE: Dysgeusia, Fatigue... AEs leading to discontinuation/dose reduction: Dysgeusia (all grades, 46%) Sources: Fatigue (grade 3, 4%) Nausea (grade 3, 1%) Vomiting (grade 3, 1%) Creatine kinase increased (grade 3-4, 8%) Lipase increased (grade 3-4, 13%) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Arthralgia, Dysphagia... AEs leading to discontinuation/dose reduction: Arthralgia (1 patient) Sources: Dysphagia (1 patient) General physical health deterioration (1 patient) Abdominal pain upper (1 patient) Agitation (1 patient) Depression (1 patient) Dry mouth (1 patient) Lumbar vertebral fracture (1 patient) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Rhabdomyolysis, Dizziness... AEs leading to discontinuation/dose reduction: Rhabdomyolysis (1%) Sources: Dizziness (1%) Pneumonia (1%) Muscular weakness (1%) |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Blood uric acid increased, Angina pectoris... AEs leading to discontinuation/dose reduction: Blood uric acid increased (1%) Sources: Angina pectoris (1%) Anorectal infection (1%) Back pain (1%) Bile duct stone (1%) Cough (1%) Disturbance in attention (1%) Femoral neck fracture (1%) Gastric ulcer (1%) Influenza (1%) Sleep disorder (1%) Spinal compression fracture (1%) Upper respiratory tract infection (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Rhabdomyolysis | 3 patients | 3000 mg 1 times / day multiple, oral Highest studied dose Dose: 3000 mg, 1 times / day Route: oral Route: multiple Dose: 3000 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatine kinase increased | grade 3-4, 1 patient | 3000 mg 1 times / day multiple, oral Highest studied dose Dose: 3000 mg, 1 times / day Route: oral Route: multiple Dose: 3000 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Arthralgia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Asthenia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dysphagia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
General physical health deterioration | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatine kinase increased | 2% DLT, Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Ageusia | 2% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dehydration | 2% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Fatigue | 2% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Nausea | 4% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Decreased appetite | 5% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dysgeusia | 5% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Weight decreased | 5% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alopecia | 6% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Muscle spasms | 9% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Anemia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Constipation | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hypertension | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hypogeusia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Amylase increased | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Blood uric acid increased | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dizziness | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dyspnea | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Gastroenteritis viral | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hypogeusia | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Malaise | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Muscular weakness | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Myoglobin blood increased | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rhabdomyolysis | 1% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alanine aminotransferase increased | 2% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Aspartate aminotransferase increased | 2% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Myalgia | 3% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | 5% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Vomiting | 7% Disc. AE |
800 mg 1 times / day steady, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: steady Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Asthenia | 4% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Aspartate aminotransferase increased | all grades, 19% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Alanine aminotransferase increased | grade 3-4, 4% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Amylase increased | grade 3-4, 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Pruritus | all grades, 10% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Vomiting | all grades, 11% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Pain | all grades, 14% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Headache | all grades, 15% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Amylase increased | all grades, 16% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Abdominal pain | all grades, 18% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alanine aminotransferase increased | all grades, 19% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Myalgia | all grades, 19% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Decreased appetite | all grades, 23% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lymphopenia | all grades, 28% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Weight decreased | all grades, 30% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Anemia | all grades, 32% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | all grades, 32% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Musculoskeletal pain | all grades, 32% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Nausea | all grades, 39% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Fatigue | all grades, 41% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lipase increased | all grades, 43% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hyperglycemia | all grades, 51% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alopecia | all grades, 53% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Muscle spasms | all grades, 54% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatine kinase increased | all grades, 61% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Increased serum creatinine | all grades, 92% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Headache | grade 3, 1% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Musculoskeletal pain | grade 3, 1% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Pain | grade 3, 1% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Decreased appetite | grade 3, 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | grade 3, 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Muscle spasms | grade 3, 3% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Weight decreased | grade 3, 3% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lymphopenia | grade 3-4, 3% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Aspartate aminotransferase increased | grade 3-4, 4% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hyperglycemia | grade 3-4, 4% | 200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dysgeusia | all grades, 46% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Nausea | grade 3, 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Vomiting | grade 3, 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Fatigue | grade 3, 4% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Lipase increased | grade 3-4, 13% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Creatine kinase increased | grade 3-4, 8% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Abdominal pain upper | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Agitation | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Arthralgia | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Depression | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dry mouth | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dysphagia | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
General physical health deterioration | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lumbar vertebral fracture | 1 patient Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dizziness | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Muscular weakness | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Pneumonia | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rhabdomyolysis | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Angina pectoris | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Anorectal infection | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Back pain | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Bile duct stone | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Blood uric acid increased | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Cough | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disturbance in attention | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Femoral neck fracture | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Gastric ulcer | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Influenza | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Sleep disorder | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Spinal compression fracture | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Upper respiratory tract infection | 1% Disc. AE |
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy 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 | ||||
no | ||||
no | ||||
no | ||||
yes [IC50 1.5 uM] | ||||
yes [Ki 0.045 uM] | unknown (co-administration study) Comment: study to assess the effects of sonidegib on the PK of a CYP2B6 and a CYP2C9 probe substrate is ongoing Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205266Orig1s000ClinPharmR.pdf#page=7 Page: - |
|||
yes [Ki 1.7 uM] | unknown (co-administration study) Comment: study to assess the effects of sonidegib on the PK of a CYP2B6 and a CYP2C9 probe substrate is ongoing Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205266Orig1s000ClinPharmR.pdf#page=7 Page: - |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: Sonidegib is metabolized by CYP3A4 to several inactive metabolites. Ketoconazole increased sonidegib AUC0-10d by 2.2-fold and rifampicin decreased sonidegib AUC0-10d by 72% following a single 800 mg dose in healthy subjects. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205266Orig1s000ClinPharmR.pdf#page=7 Page: - |
|||
no | ||||
no | ||||
no |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sample Use Guides
Recommended dose: 200 mg orally once daily taken on an empty stomach, at least 1 hour before or 2 hours after a meal.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900187
Sonidegib inhibits TM3 luciferized cell line with 0.6 nM and 8 nM, at the presence of 1 nM and 25 nM Hh agonist Ag1.5, respectively.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 19:43:10 GMT 2025
by
admin
on
Mon Mar 31 19:43:10 GMT 2025
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Record UNII |
0RLU3VTK5M
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Record Status |
Validated (UNII)
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Record Version |
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-
Download
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Official Name | English | ||
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Preferred Name | English | ||
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Code | English | ||
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Code | English | ||
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Common Name | English | ||
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Code | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Code | English | ||
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Code | English | ||
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Common Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2189
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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WHO-ATC |
L01XX48
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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NDF-RT |
N0000184149
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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FDA ORPHAN DRUG |
468814
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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Code System | Code | Type | Description | ||
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Sonidegib
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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DTXSID501009335
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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0RLU3VTK5M
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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1659191
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | RxNorm | ||
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90863
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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8199
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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N0000184148
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | Smoothened Receptor Antagonists [MoA] | ||
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CHEMBL2105737
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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DB09143
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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956697-53-3
Created by
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PRIMARY | |||
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100000145390
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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5008
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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SONIDEGIB
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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EU/3/09/697(WITHDRAWN)
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | Treatment of naevoid basal-cell carcinoma syndrome (Gorlin syndrome) 24/11/2009 Withdrawn | ||
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0RLU3VTK5M
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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m11843
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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C82385
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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24775005
Created by
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PRIMARY | |||
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YY-63
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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9394
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY | |||
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SUB123432
Created by
admin on Mon Mar 31 19:43:10 GMT 2025 , Edited by admin on Mon Mar 31 19:43:10 GMT 2025
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PRIMARY |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> NON-INDUCER |
compared to positive controls
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> NON-INDUCER |
compared to positive controls
|
||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> INHIBITOR |
Ki
|
||
|
METABOLIC ENZYME -> SUBSTRATE |
metabolism by CYP3A4 (at least 29% of its overall metabolism); Ketoconazole(CYP 3A4 inhibition) increased sonidegib exposure 2.2-fold;Rifampin (CYP 3A4 induction) reduced exposure by 72%
|
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METABOLIC ENZYME -> NON-INHIBITOR |
No time dependent inhibition upto 50 micromolar
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METABOLIC ENZYME -> INHIBITOR |
Ki
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE ACTIVE -> PARENT |
LNC-119 AND LMT-326 ACCOUNTED FOR 14% OF THE AUC
PLASMA
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METABOLITE INACTIVE -> PARENT |
MAJOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
PLASMA
|
Related Record | Type | Details | ||
---|---|---|---|---|
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Biological Half-life | PHARMACOKINETIC |
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