U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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
Structure of Vismodegib

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)

HIDE SMILES / InChI

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

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

2012
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
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
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

Sample Use Guides

150 mg orally once daily
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Wed Apr 02 08:40:16 GMT 2025
Edited
by admin
on Wed Apr 02 08:40:16 GMT 2025
Record UNII
25X868M3DS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Erivedge
Preferred Name English
Vismodegib
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
GDC-0449
Code English
Vismodegib [INN]
Common Name English
Vismodegib [VANDF]
Common Name English
Vismodegib [WHO-DD]
Common Name English
2-Chloro-n-(4-chloro-3-pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide
Systematic 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
2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide
Systematic Name English
Vismodegib [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
LIVERTOX NBK548629
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
EMA ASSESSMENT REPORTS ERIVEDGE (AUTHORIZED: CARCINOMA, BASAL CELL)
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
NDF-RT N0000184149
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
WHO-ATC L01XX43
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
WHO-VATC QL01XX43
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
Code System Code Type Description
CAS
879085-55-9
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
DRUG BANK
DB08828
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
DRUG CENTRAL
4227
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
HSDB
8130
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
DAILYMED
25X868M3DS
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
EVMPD
SUB32354
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
INN
9311
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
USAN
WW-37
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
MERCK INDEX
m11477
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY Merck Index
NDF-RT
N0000184148
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY Smoothened Receptor Antagonists [MoA]
PUBCHEM
24776445
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID40236689
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
CHEBI
66903
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
SMS_ID
100000124371
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
WIKIPEDIA
Vismodegib
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
NSC
755986
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
NSC
747691
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
ChEMBL
CHEMBL473417
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
RXCUI
1242987
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY RxNorm
IUPHAR
6975
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
LACTMED
Vismodegib
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
FDA UNII
25X868M3DS
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
NCI_THESAURUS
C74038
Created by admin on Wed Apr 02 08:40:16 GMT 2025 , Edited by admin on Wed Apr 02 08:40:16 GMT 2025
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MINOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
REAGENT->PARENT
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

Volume of Distribution PHARMACOKINETIC