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Details

Stereochemistry ACHIRAL
Molecular Formula C19H14Cl2N2O3S
Molecular Weight 421.2987
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VISMODEGIB

SMILES

CS(=O)(=O)c1ccc(c(c1)Cl)C(=Nc2ccc(c(c2)-c3ccccn3)Cl)O

InChI

InChIKey=BPQMGSKTAYIVFO-UHFFFAOYSA-N
InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/24857041

Vismodegib (trade name Erivedge) is a drug for the treatment of basal-cell carcinoma (BCC). It was approved by FDA on January 30, 2012 and by the European Commission on 12 July 2013, for the treatment of adult patients with symptomatic metastatic BCC, or locally advanced BCC inappropriate for surgery or radiotherapy. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011. The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ERIVEDGE

Approved Use

ERIVEDGE capsule is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Launch Date

1.32788165E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.95 μM
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VISMODEGIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2850 μM × h
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VISMODEGIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.3 day
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VISMODEGIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.45%
VISMODEGIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
170 mg/m2 1 times / day multiple, oral
Dose: 170 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 170 mg/m2, 1 times / day
Sources:
unhealthy, 11.6 years (range: 4.4–21 years)
n = 7
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 11.6 years (range: 4.4–21 years)
Sex: M+F
Population Size: 7
Sources:
DLT: Gamma-glutamyltransferase increased...
Dose limiting toxicities:
Gamma-glutamyltransferase increased (grade 3)
Sources:
150 mg 1 times / day multiple, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 14.5 years (range: 3.9–20.3 years)
n = 10
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 14.5 years (range: 3.9–20.3 years)
Sex: M+F
Population Size: 10
Sources:
DLT: Hypokalemia...
Dose limiting toxicities:
Hypokalemia (grade 4)
Sources:
300 mg 1 times / day multiple, oral
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, 14.5 years (range: 3.9–20.3 years)
n = 10
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 14.5 years (range: 3.9–20.3 years)
Sex: M+F
Population Size: 10
Sources:
DLT: Thrombocytopenia...
Dose limiting toxicities:
Thrombocytopenia (grade 3)
Sources:
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Other AEs: Nausea, Nausea...
Other AEs:
Nausea (grade 1-2, 29.7%)
Nausea (grade 3, 0.7%)
Diarrhea (grade 1-2, 28.3%)
Diarrhea (grade 3, 0.7%)
Constipation (grade 1-2, 21%)
Vomiting (grade 1-2, 13.8%)
Fatigue (grade 1-2, 34.1%)
Fatigue (grade 3, 5.1%)
Fatigue (grade 4, 0.7%)
Weight loss (grade 1-2, 42.2%)
Weight loss (grade 3, 7.2%)
Decreased appetite (grade 1-2, 23.2%)
Decreased appetite (grade 3, 2.2%)
Muscle spasms (grade 1-2, 68.1%)
Muscle spasms (grade 3, 3.6%)
Arthralgia (grade 1-2, 15.2%)
Arthralgia (grade 3, 0.7%)
Dysgeusia (grade 1-2, 55.1%)
Ageusia (grade 1-2, 10.9%)
Alopecia (grade 1-2, 63.8%)
Hyponatremia (grade 3, 4%)
Hypokalemia (grade 3, 1%)
Azotemia (grade 3, 2%)
Sources:
540 mg single, oral
Highest studied dose
Dose: 540 mg
Route: oral
Route: single
Dose: 540 mg
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: locally advanced or metastatic basal cell carcinoma
Age Group: adult
Population Size: 4
Sources:
150 mg 1 times / day multiple, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
pregnant
Other AEs: Birth defects...
Other AEs:
Birth defects (grade 5|severe)
Sources:
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy
n = 10
Health Status: unhealthy
Sex: F
Population Size: 10
Sources:
Other AEs: Amenorrhea...
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Disc. AE: Metastatic malignant melanoma, Ischaemic stroke...
AEs leading to
discontinuation/dose reduction:
Metastatic malignant melanoma (grade 4, 1 patient)
Ischaemic stroke (grade 3, 1 patient)
Fatigue (grade 3, 1 patient)
Muscle spasms (grade 3, 2 patients)
Metastatic squamous cell carcinoma (grade 4, 1 patient)
Acute myocardial infarction (grade 5, 1 patient)
Dysgeusia (grade 1, 1 patient)
Weight decreased (grade 2, 1 patient)
Asthenia (grade 3, 1 patient)
Aphagia (grade 3, 1 patient)
Paraesthesia (grade 2, 1 patient)
Cellulitis (grade 3, 1 patient)
Hypovolaemic shock (grade 5, 1 patient)
Sources: Page: p. 91
AEs

AEs

AESignificanceDosePopulation
Gamma-glutamyltransferase increased grade 3
DLT
170 mg/m2 1 times / day multiple, oral
Dose: 170 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 170 mg/m2, 1 times / day
Sources:
unhealthy, 11.6 years (range: 4.4–21 years)
n = 7
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 11.6 years (range: 4.4–21 years)
Sex: M+F
Population Size: 7
Sources:
Hypokalemia grade 4
DLT
150 mg 1 times / day multiple, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 14.5 years (range: 3.9–20.3 years)
n = 10
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 14.5 years (range: 3.9–20.3 years)
Sex: M+F
Population Size: 10
Sources:
Thrombocytopenia grade 3
DLT
300 mg 1 times / day multiple, oral
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, 14.5 years (range: 3.9–20.3 years)
n = 10
Health Status: unhealthy
Condition: Medulloblastoma
Age Group: 14.5 years (range: 3.9–20.3 years)
Sex: M+F
Population Size: 10
Sources:
Ageusia grade 1-2, 10.9%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Vomiting grade 1-2, 13.8%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Arthralgia grade 1-2, 15.2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Constipation grade 1-2, 21%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Decreased appetite grade 1-2, 23.2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Diarrhea grade 1-2, 28.3%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Nausea grade 1-2, 29.7%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Fatigue grade 1-2, 34.1%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Weight loss grade 1-2, 42.2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Dysgeusia grade 1-2, 55.1%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Alopecia grade 1-2, 63.8%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Muscle spasms grade 1-2, 68.1%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Arthralgia grade 3, 0.7%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Diarrhea grade 3, 0.7%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Nausea grade 3, 0.7%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Hypokalemia grade 3, 1%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Azotemia grade 3, 2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Decreased appetite grade 3, 2.2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Muscle spasms grade 3, 3.6%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Hyponatremia grade 3, 4%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Fatigue grade 3, 5.1%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Weight loss grade 3, 7.2%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Fatigue grade 4, 0.7%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 61 years (range: 21 - 101 years)
n = 138
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Age Group: 61 years (range: 21 - 101 years)
Sex: M+F
Population Size: 138
Sources:
Birth defects grade 5|severe
150 mg 1 times / day multiple, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
pregnant
Amenorrhea 3 patients
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy
n = 10
Health Status: unhealthy
Sex: F
Population Size: 10
Sources:
Dysgeusia grade 1, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Paraesthesia grade 2, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Weight decreased grade 2, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Aphagia grade 3, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Asthenia grade 3, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Cellulitis grade 3, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Fatigue grade 3, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Ischaemic stroke grade 3, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Muscle spasms grade 3, 2 patients
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Metastatic malignant melanoma grade 4, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Metastatic squamous cell carcinoma grade 4, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Acute myocardial infarction grade 5, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Hypovolaemic shock grade 5, 1 patient
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 91
unhealthy
n = 104
Health Status: unhealthy
Condition: Advanced Basal Cell Carcinoma
Sex: M+F
Population Size: 104
Sources: Page: p. 91
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
inconclusive
inconclusive
no [IC50 83.3 uM]
no
yes
yes
yes
no (co-administration study)
Comment: In vivo studies indicate that there was no clinically meaningful difference in the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, ethinyl estradiol, or norethindrone when co-administered with vismodegib.
Page: 21.0
yes
unlikely
Comment: The applicant states that this finding is unlikely to be of clinical relevance due to the high degree of plasma protein binding of vismodegib and the low confirmed clinical occurrence of BCRP based drug-drug interactions.
Page: 57.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
no (co-administration study)
Comment: the steady state concentrations of total and unbound vismodegib for patients taking a P-gp inhibitor concomitantly with vismodegib were within the range of concentrations of patients taking vismodegib alone.
Page: 21.0
yes
unlikely
Comment: Vismodegib was identified to be a substrate of CYP2C9 and CYP3A4; however, CYP inhibition would unlikely alter vismodegib concentrations because of its slow elimination via multiple pathways, including minor metabolism by several CYPs and main excretion of unchanged drug.
Page: 21.0
yes
unlikely
Comment: Vismodegib was identified to be a substrate of CYP2C9 and CYP3A4; however, CYP inhibition would unlikely alter vismodegib concentrations because of its slow elimination via multiple pathways, including minor metabolism by several CYPs and main excretion of unchanged drug.
Page: 21.0
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells.
2011 Jan 13
The dawn of hedgehog inhibitors: Vismodegib.
2013 Jan
The Hedgehog pathway: role in cell differentiation, polarity and proliferation.
2015 Feb
Patents

Sample Use Guides

150 mg orally once daily
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
VISMODEGIB
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
GDC-0449
Code English
ERIVEDGE
Brand Name English
VISMODEGIB [WHO-DD]
Common Name English
VISMODEGIB [INN]
Common Name English
VISMODEGIB [VANDF]
Common Name English
2-CHLORO-N-(4-CHLORO-3-PYRIDIN-2-YL)PHENYL)-4-(METHYLSULFONYL)BENZAMIDE
Common Name English
BENZAMIDE, 2-CHLORO-N-(4-CHLORO-3-(2-PYRIDINYL)PHENYL)-4-(METHYLSULFONYL)-
Systematic Name English
NSC-755986
Code English
VISMODEGIB [USAN]
Common Name English
NSC-747691
Code English
VISMODEGIB [MI]
Common Name English
VISMODEGIB [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
LIVERTOX 1032
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
EMA ASSESSMENT REPORTS ERIVEDGE (AUTHORIZED: CARCINOMA, BASAL CELL)
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
NDF-RT N0000184149
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
WHO-ATC L01XX43
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
WHO-VATC QL01XX43
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
Code System Code Type Description
CAS
879085-55-9
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
DRUG BANK
DB08828
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
DRUG CENTRAL
4227
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
HSDB
8130
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
EVMPD
SUB32354
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
INN
9311
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
MERCK INDEX
M11477
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000184148
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY Smoothened Receptor Antagonists [MoA]
PUBCHEM
24776445
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
EPA CompTox
879085-55-9
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
WIKIPEDIA
Vismodegib
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
ChEMBL
CHEMBL473417
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
RXCUI
1242987
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY RxNorm
IUPHAR
6975
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
LACTMED
Vismodegib
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
FDA UNII
25X868M3DS
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY
NCI_THESAURUS
C74038
Created by admin on Fri Jun 25 21:51:20 UTC 2021 , Edited by admin on Fri Jun 25 21:51:20 UTC 2021
PRIMARY