Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H14Cl2N2O3S |
Molecular Weight | 421.297 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(=O)(=O)C1=CC(Cl)=C(C=C1)C(=O)NC2=CC(=C(Cl)C=C2)C3=NC=CC=C3
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)
Molecular Formula | C19H14Cl2N2O3S |
Molecular Weight | 421.297 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/24857041
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL5971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19443052 |
3.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | ERIVEDGE Approved UseERIVEDGE 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 Date2012 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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5.95 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22458643 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2850 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22458643 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.3 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22458643 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.45% |
VISMODEGIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=37 Page: 37.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Preclinical assessment of the absorption, distribution, metabolism and excretion of GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide), an orally bioavailable systemic Hedgehog signalling pathway inhibitor. | 2009 Nov |
|
Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. | 2009 Sep 17 |
|
Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. | 2011 |
|
Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells. | 2011 Jan 13 |
|
Effects of the Hedgehog pathway inhibitor GDC-0449 on lung cancer cell lines are mediated by side populations. | 2012 Mar |
|
The dawn of hedgehog inhibitors: Vismodegib. | 2013 Jan |
|
The Hedgehog pathway: role in cell differentiation, polarity and proliferation. | 2015 Feb |
Patents
Substance Class |
Chemical
Created
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Wed Apr 02 08:40:16 GMT 2025
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Record UNII |
25X868M3DS
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Record Status |
Validated (UNII)
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NCI_THESAURUS |
C2189
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LIVERTOX |
NBK548629
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EMA ASSESSMENT REPORTS |
ERIVEDGE (AUTHORIZED: CARCINOMA, BASAL CELL)
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NDF-RT |
N0000184149
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WHO-ATC |
L01XX43
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WHO-VATC |
QL01XX43
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DB08828
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m11477
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N0000184148
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PRIMARY | Smoothened Receptor Antagonists [MoA] | ||
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24776445
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100000124371
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Vismodegib
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755986
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CHEMBL473417
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6975
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Vismodegib
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25X868M3DS
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C74038
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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REAGENT->PARENT |
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
MINOR
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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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Biological Half-life | PHARMACOKINETIC |
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SINGLE DOSE |
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Volume of Distribution | PHARMACOKINETIC |
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