Vismodegib

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203388s005s006s007s008lbl.pdf
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
Smoothened homolog 20 Target ID: CHEMBL5971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19443052	Inhibitor 8504		3.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Basal cell carcinoma 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203388s005s006s007s008lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

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

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.45% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21753154/			VISMODEGIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193 inhibitor 2438	substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP2C19 2057 P-gp 1741 BCRP 910	CYP3A4/5 91 P-gp 2052 CYP2C18 149 CYP2C19 1119	CYP1A2 832 CYP2B6 669 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	inconclusive
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	inconclusive
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	inconclusive
PXR 51	binder 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=47 Page: 47.0	no [IC50 83.3 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	yes
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	yes
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=21 Page: 21.0
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=57 Page: 57.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=57 Page: 57.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C18 149	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	yes
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	yes
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=46 Page: 46.0	yes
P-gp 2052	substrate 4014 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
CYP2C9 1193	substrate 4014 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
CYP3A4/5 91	substrate 4014 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
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203388Orig1s000ClinPharmR.pdf#page=37 Page: 37.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:66903	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66903
ChemicalBook	CB52500590	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52500590
eMolecules	32176457	https://www.emolecules.com/cgi-bin/more?vid=32176457
MolPort	MolPort-009-679-417	https://www.molport.com/shop/molecule-link/MolPort-009-679-417
MolPort	MolPort-047-116-774	https://www.molport.com/shop/molecule-link/MolPort-047-116-774
Selleck Chemicals	GDC-0449	http://www.selleckchem.com/products/GDC-0449.html
ZINC	ZINC000040899447	http://zinc15.docking.org/substances/ZINC000040899447

PubMed

Title	Date	PubMed
		252160199
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	19845436
Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.	2009 Sep 17	19726763
Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms.	2011	22087285
Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells.	2011 Jan 13	21249152
Effects of the Hedgehog pathway inhibitor GDC-0449 on lung cancer cell lines are mediated by side populations.	2012 Mar	21519961
The dawn of hedgehog inhibitors: Vismodegib.	2013 Jan	23662017
The Hedgehog pathway: role in cell differentiation, polarity and proliferation.	2015 Feb	25559776

Patents

Sample Use Guides

In Vivo Use Guide

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

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Name

Type

Language

Erivedge

Preferred Name

English

Vismodegib

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