Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H15BrF2N4O3 |
Molecular Weight | 441.227 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C=NC2=C1C=C(C(=O)NOCCO)C(NC3=CC=C(Br)C=C3F)=C2F
InChI
InChIKey=ACWZRVQXLIRSDF-UHFFFAOYSA-N
InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
Molecular Formula | C17H15BrF2N4O3 |
Molecular Weight | 441.227 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C84865 | https://www.ncbi.nlm.nih.gov/pubmed/23635776 | https://acr.confex.com/acr/2006/webprogram/Paper5558.html
Curator's Comment: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C84865 | https://www.ncbi.nlm.nih.gov/pubmed/23635776 | https://acr.confex.com/acr/2006/webprogram/Paper5558.html
Binimetinib (MEK162) is an oral small-molecule with potential antineoplastic activity. It is a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS. MEK162 at 6 mg/kg, BID combined with BEZ235 (dual PI3K/mTOR inhibitor) resulted in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. There are three ongoing Phase 3 trials with binimetinib in advanced cancer patients: NEMO (NRAS-mutant melanoma), COLUMBUS (encorafenib in combination with binimetinib in BRAF-mutant melanoma) and BEACON CRC (encorafenib, binimetinib and cetuximab in BRAF-mutant colorectal cancer).
CNS Activity
Sources: http://www.laurensfirstandgoal.org/Resources/dana%20farber%20Lauren's%20First%20and%20Goal_2015_FINAL.pdf
Curator's Comment: Preclinical studies of MEK162 in patients with
the BRAF fusion gene have revealed that this novel drug
might be able to penetrate the blood-brain barrier, which has encouraged investigators to explore this therapeutic candidate.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3956 |
12.0 nM [IC50] | ||
Target ID: CHEMBL2964 |
12.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | MEKTOVI Approved Useis indicated, in combination with encorafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test Launch Date2018 |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
545 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28152546 |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BINIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
241 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28152546 |
45 mg 2 times / day multiple, oral dose: 45 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BINIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1710 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28152546 |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BINIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
964 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28152546 |
45 mg 2 times / day multiple, oral dose: 45 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
BINIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
DLT: Chorioretinopathy, Dermatitis acneiform... Disc. AE: Macular oedema, Nausea... Other AEs: Retinal deposits, Retinopathy... Dose limiting toxicities: Chorioretinopathy (grade 3, 25%) AEs leading toDermatitis acneiform (grade 3, 25%) discontinuation/dose reduction: Macular oedema (grade 3-4, 25%) Other AEs:Nausea (grade 1-2, 25%) Vomiting (grade 1-2, 50%) Fatigue (grade 1-2, 25%) Retinal deposits (grade 3-4, 25%) Sources: Retinopathy (grade 3-4, 25%) Papilloedema (grade 3-4, 25%) Retinal detachment (grade 3-4, 25%) Retinal disorder (grade 3-4, 25%) Acne (grade 3-4, 25%) Skin exfoliation (grade 3-4, 25%) Diarrhoea (grade 1-2, 25%) Peripheral oedema (grade 1-2, 50%) Abdominal pain (grade 1-2, 25%) Anorexia (grade 1-2, 25%) Dyspnoea (grade 1-2, 25%) |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Disc. AE: Dermatitis acneiform, Acne... Other AEs: Diarrhoea, Peripheral oedema... AEs leading to discontinuation/dose reduction: Dermatitis acneiform (grade 1-2, 85%) Other AEs:Acne (grade 1-2, 85%) Skin exfoliation (grade 1-2, 85%) Dermatitis acneiform (grade 3-4, 2%) Acne (grade 3-4, 2%) Skin exfoliation (grade 3-4, 2%) Nausea (grade 1-2, 51%) Vomiting (grade 1-2, 49%) Fatigue (grade 1-2, 39%) Fatigue (grade 3-4, 2%) Diarrhoea (grade 1-2, 61%) Sources: Peripheral oedema (grade 1-2, 51%) Anaemia (grade 1-2, 12%) Anaemia (grade 3-4, 24%) Abdominal pain (grade 1-2, 17%) Abdominal pain (grade 3-4, 7%) Anorexia (grade 1-2, 20%) Constipation (grade 1-2, 20%) Constipation (grade 3-4, 5%) Dyspnoea (grade 1-2, 15%) Dyspnoea (grade 3-4, 2%) Pyrexia (grade 1-2, 17%) Pyrexia (grade 3-4, 2%) Dizziness (grade 1-2, 22%) Pulmonary embolism (grade 4, 1 patient) Generalised oedema (grade 4, 1 patient) |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Disc. AE: Retinal deposits, Retinopathy... Other AEs: Papilloedema, Retinal disorder... AEs leading to discontinuation/dose reduction: Retinal deposits (grade 1-2, 27%) Other AEs:Retinopathy (grade 1-2, 27%) Chorioretinopathy (grade 1-2, 27%) Macular oedema (grade 1-2, 27%) Retinal detachment (grade 1-2, 27%) Papilloedema (grade 1-2, 27%) Sources: Retinal disorder (grade 1-2, 27%) |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Disc. AE: Chorioretinopathy, Macular oedema... Other AEs: Retinal deposits, Retinopathy... AEs leading to discontinuation/dose reduction: Chorioretinopathy (grade 1-2, 11%) Other AEs:Macular oedema (grade 1-2, 11%) Retinal detachment (grade 1-2, 11%) Dermatitis acneiform (grade 1-2, 75%) Acne (grade 1-2, 75%) Skin exfoliation (grade 1-2, 75%) Dermatitis acneiform (grade 3-4, 2%) Acne (grade 3-4, 2%) Skin exfoliation (grade 3-4, 2%) Nausea (grade 1-2, 61%) Vomiting (grade 1-2, 52%) Diarrhoea (grade 1-2, 39%) Fatigue (grade 1-2, 41%) Fatigue (grade 3-4, 5%) Retinal deposits (grade 1-2, 11%) Sources: Retinopathy (grade 1-2, 11%) Papilloedema (grade 1-2, 11%) Retinal disorder (grade 1-2, 11%) Peripheral oedema (grade 1-2, 45%) Anaemia (grade 1-2, 11%) Anaemia (grade 3-4, 7%) Abdominal pain (grade 1-2, 16%) Abdominal pain (grade 3-4, 2%) Anorexia (grade 1-2, 18%) Constipation (grade 1-2, 14%) Dyspnoea (grade 1-2, 11%) Dyspnoea (grade 3-4, 5%) Pyrexia (grade 1-2, 16%) Dizziness (grade 1-2, 11%) |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Left ventricular dysfunction, Serous retinopathy... Other AEs: Fatigue, Pyrexia... AEs leading to discontinuation/dose reduction: Left ventricular dysfunction (6%) Other AEs:Serous retinopathy (5%) Left ventricular dysfunction (3%) Serous retinopathy (3%) Colitis (2%) Hemorrhage (2%) Headache (1%) Fatigue (grade 3-4, 3%) Sources: Pyrexia (grade 3-4, 4%) Peripheral edema (grade 3-4, 1%) Fatigue (all grades, 43%) Pyrexia (all grades, 18%) Peripheral edema (all grades, 13%) Nausea (grade 3-4, 2%) Diarrhea (grade 3-4, 3%) Vomiting (grade 3-4, 2%) Abdominal pain (grade 3-4, 4%) Nausea (all grades, 41%) Diarrhea (all grades, 36%) Vomiting (all grades, 30%) Abdominal pain (all grades, 28%) Constipation (all grades, 22%) Rash (grade 3-4, 1%) Rash (all grades, 22%) Dizziness (grade 3-4, 3%) Dizziness (all grades, 15%) Visual impairment (all grades, 20%) Serous retinopathy (grade 3-4, 3%) Serous retinopathy (all grades, 20%) Hemorrhage (grade 3-4, 3%) Hemorrhage (all grades, 19%) Hypertension (grade 3-4, 6%) Hypertension (all grades, 11%) Anemia (grade 3-4, 3.6%) Anemia (all grades, 36%) Leukopenia (all grades, 13%) Lymphopenia (grade 3-4, 2.1%) Lymphopenia (all grades, 13%) Neutropenia (grade 3-4, 3.1%) Neutropenia (all grades, 13%) Creatinine increased (grade 3-4, 3.6%) Creatinine increased (all grades, 93%) Creatine phosphokinase increased (grade 3-4, 5%) Creatine phosphokinase increased (all grades, 58%) Gamma-glutamyltransferase increased (grade 3-4, 11%) Gamma-glutamyltransferase increased (all grades, 45%) ALT increased (grade 3-4, 6%) ALT increased (all grades, 29%) AST increased (grade 3-4, 2.6%) AST increased (all grades, 27%) Alkaline phosphatase increased (grade 3-4, 0.5%) Alkaline phosphatase increased (all grades, 21%) Hyponatremia (grade 3-4, 3.6%) Hyponatremia (all grades, 18%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abdominal pain | grade 1-2, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anorexia | grade 1-2, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Diarrhoea | grade 1-2, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dyspnoea | grade 1-2, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Fatigue | grade 1-2, 25% Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Nausea | grade 1-2, 25% Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Peripheral oedema | grade 1-2, 50% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Vomiting | grade 1-2, 50% Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Chorioretinopathy | grade 3, 25% DLT, Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dermatitis acneiform | grade 3, 25% DLT, Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Acne | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Papilloedema | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal deposits | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal detachment | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal disorder | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinopathy | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Skin exfoliation | grade 3-4, 25% | 80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Macular oedema | grade 3-4, 25% Disc. AE |
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anaemia | grade 1-2, 12% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dyspnoea | grade 1-2, 15% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Abdominal pain | grade 1-2, 17% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Pyrexia | grade 1-2, 17% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anorexia | grade 1-2, 20% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Constipation | grade 1-2, 20% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dizziness | grade 1-2, 22% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Fatigue | grade 1-2, 39% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Vomiting | grade 1-2, 49% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Peripheral oedema | grade 1-2, 51% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Nausea | grade 1-2, 51% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Diarrhoea | grade 1-2, 61% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Acne | grade 1-2, 85% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dermatitis acneiform | grade 1-2, 85% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Skin exfoliation | grade 1-2, 85% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dyspnoea | grade 3-4, 2% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Pyrexia | grade 3-4, 2% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Acne | grade 3-4, 2% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dermatitis acneiform | grade 3-4, 2% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Fatigue | grade 3-4, 2% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Skin exfoliation | grade 3-4, 2% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anaemia | grade 3-4, 24% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Constipation | grade 3-4, 5% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Abdominal pain | grade 3-4, 7% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Generalised oedema | grade 4, 1 patient | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Pulmonary embolism | grade 4, 1 patient | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Papilloedema | grade 1-2, 27% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal disorder | grade 1-2, 27% | 60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Chorioretinopathy | grade 1-2, 27% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Macular oedema | grade 1-2, 27% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal deposits | grade 1-2, 27% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal detachment | grade 1-2, 27% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinopathy | grade 1-2, 27% Disc. AE |
60 mg 2 times / day steady, oral MTD Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anaemia | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dizziness | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dyspnoea | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Papilloedema | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal deposits | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal disorder | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinopathy | grade 1-2, 11% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Chorioretinopathy | grade 1-2, 11% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Macular oedema | grade 1-2, 11% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Retinal detachment | grade 1-2, 11% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Constipation | grade 1-2, 14% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Abdominal pain | grade 1-2, 16% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Pyrexia | grade 1-2, 16% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anorexia | grade 1-2, 18% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Diarrhoea | grade 1-2, 39% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Fatigue | grade 1-2, 41% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Peripheral oedema | grade 1-2, 45% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Vomiting | grade 1-2, 52% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Nausea | grade 1-2, 61% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Acne | grade 1-2, 75% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dermatitis acneiform | grade 1-2, 75% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Skin exfoliation | grade 1-2, 75% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Abdominal pain | grade 3-4, 2% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Acne | grade 3-4, 2% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dermatitis acneiform | grade 3-4, 2% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Skin exfoliation | grade 3-4, 2% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Dyspnoea | grade 3-4, 5% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Fatigue | grade 3-4, 5% Disc. AE |
45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Anaemia | grade 3-4, 7% | 45 mg 2 times / day steady, oral RP2D Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy, 58 years (range: 30–86 years) Health Status: unhealthy Age Group: 58 years (range: 30–86 years) Sex: M+F Sources: |
Headache | 1% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Colitis | 2% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hemorrhage | 2% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Left ventricular dysfunction | 3% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Serous retinopathy | 3% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Serous retinopathy | 5% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Left ventricular dysfunction | 6% Disc. AE |
45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hypertension | all grades, 11% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Leukopenia | all grades, 13% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lymphopenia | all grades, 13% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Neutropenia | all grades, 13% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Peripheral edema | all grades, 13% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dizziness | all grades, 15% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hyponatremia | all grades, 18% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Pyrexia | all grades, 18% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hemorrhage | all grades, 19% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Serous retinopathy | all grades, 20% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Visual impairment | all grades, 20% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alkaline phosphatase increased | all grades, 21% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Constipation | all grades, 22% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rash | all grades, 22% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
AST increased | all grades, 27% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Abdominal pain | all grades, 28% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
ALT increased | all grades, 29% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Vomiting | all grades, 30% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Anemia | all grades, 36% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | all grades, 36% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Nausea | all grades, 41% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Fatigue | all grades, 43% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Gamma-glutamyltransferase increased | all grades, 45% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatine phosphokinase increased | all grades, 58% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatinine increased | all grades, 93% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Alkaline phosphatase increased | grade 3-4, 0.5% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Peripheral edema | grade 3-4, 1% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rash | grade 3-4, 1% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Gamma-glutamyltransferase increased | grade 3-4, 11% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Nausea | grade 3-4, 2% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Vomiting | grade 3-4, 2% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Lymphopenia | grade 3-4, 2.1% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
AST increased | grade 3-4, 2.6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | grade 3-4, 3% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Dizziness | grade 3-4, 3% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Fatigue | grade 3-4, 3% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hemorrhage | grade 3-4, 3% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Serous retinopathy | grade 3-4, 3% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Neutropenia | grade 3-4, 3.1% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Anemia | grade 3-4, 3.6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatinine increased | grade 3-4, 3.6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hyponatremia | grade 3-4, 3.6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Abdominal pain | grade 3-4, 4% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Pyrexia | grade 3-4, 4% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatine phosphokinase increased | grade 3-4, 5% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
ALT increased | grade 3-4, 6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hypertension | grade 3-4, 6% | 45 mg 2 times / day steady, oral Recommended Dose: 45 mg, 2 times / day Route: oral Route: steady Dose: 45 mg, 2 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 | ||||
weak [IC50 18.1 uM] | ||||
weak [IC50 50 uM] | ||||
weak [IC50 50 uM] | ||||
weak [IC50 >25 uM] | ||||
weak | unlikely Comment: It is not expected for binimetinib to have a clinically relevant induction of CYP2C9, as the plasma concentrations observed in patients is well below the concentration required for minimal induction of CYP2C9 based on in vitro study Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210498Orig1s000MultidisciplineR.pdf#page=61 Page: - |
|||
yes [IC50 6 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
major | ||||
major | ||||
major | no (co-administration study) Comment: atazanavir did not alter the exposure of BINIMETINIB Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210498Orig1s000MultidisciplineR.pdf#page=54 Page: - |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | no (co-administration study) Comment: did not alter the exposure of midazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210498Orig1s000MultidisciplineR.pdf#page=41 Page: - |
|||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
MEK and the inhibitors: from bench to bedside. | 2013 Apr 12 |
|
RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. | 2013 Jun |
|
MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. | 2013 Mar |
|
Adjuvant immunotherapy of melanoma and development of new approaches using the neoadjuvant approach. | 2013 May-Jun |
|
MEK1/2 inhibitors in the treatment of gynecologic malignancies. | 2014 Apr |
|
MEK targeting in N-RAS mutated metastatic melanoma. | 2014 Mar 4 |
|
Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. | 2014 Sep 25 |
Patents
Sample Use Guides
MEK162 administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23635776
MCF7 (mutant PIK3CA) breast cancer cells exhibiting sensitivity to PI3K inhibition were seeded in 12-well plates (2 × 10^4). After 24 hours, cells were treated with BEZ235, BKM120, GDC-0941, or MK2206 alone or in combination with MEK162. MEK162 (1 uM) combined with MK-2206 (2 mM) completely reversed the resistance of RSK-expressing MCF7 cells.
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 07:07:47 GMT 2025
by
admin
on
Wed Apr 02 07:07:47 GMT 2025
|
Record UNII |
181R97MR71
|
Record Status |
Validated (UNII)
|
Record Version |
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-
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Code | English | ||
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Common Name | English | ||
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Code | English |
Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
440414
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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NCI_THESAURUS |
C69145
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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NCI_THESAURUS |
C129825
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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WHO-ATC |
L01XE41
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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FDA ORPHAN DRUG |
411613
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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FDA ORPHAN DRUG |
411513
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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Code System | Code | Type | Description | ||
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C84865
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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SUB179942
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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9764
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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181R97MR71
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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BC-93
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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606143-89-9
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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5290
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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m12078
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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10288191
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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181R97MR71
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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DTXSID70209422
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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Binimetinib
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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Binimetinib
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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PRIMARY | |||
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100000165993
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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PRIMARY | |||
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CHEMBL3187723
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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PRIMARY | |||
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145371
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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2049122
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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DB11967
Created by
admin on Wed Apr 02 07:07:47 GMT 2025 , Edited by admin on Wed Apr 02 07:07:47 GMT 2025
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PRIMARY |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
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EXCRETED UNCHANGED |
FECAL
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METABOLIC ENZYME -> INHIBITOR |
MINOR
IC50
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METABOLIC ENZYME -> SUBSTRATE |
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TRANSPORTER -> INHIBITOR |
MINOR
IC50
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BINDER->LIGAND |
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TRANSPORTER -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
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EXCRETED UNCHANGED |
URINE
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TRANSPORTER -> SUBSTRATE |
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
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METABOLITE ACTIVE -> PARENT |
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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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Volume of Distribution | PHARMACOKINETIC |
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DOSE |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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DOSE |
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