Details of the Drug

General Information of Drug (ID: DM5IXKQ)

Drug Name
Vismodegib
Synonyms
879085-55-9; GDC-0449; Erivedge; 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide; Vismodegib (GDC-0449); HhAntag691; GDC0449; GDC 0449; UNII-25X868M3DS; CHEMBL473417; CHEBI:66903; 25X868M3DS; NSC755986; AK-77261; 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-(methylsulfonyl)benzamide; C19H14Cl2N2O3S; 2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide; 2-chloro-n-(4-chloro-3-(2-pyridinyl)phenyl)-4-(methylsulfonyl)benzamide; Erivedge (TN); Vismodegib (SHH inhibitor); Gdc-0449
Indication
Disease Entry ICD 11 Status REF
Basal cell carcinoma 2C32 Approved [1]
Primitive neuroectodermal tumour medulloblastoma 2A00.11 Phase 2 [2]
Affected Organisms
Humans and other mammals
ATC Code
L01XJ01: Vismodegib
L01XJ: Hedgehog pathway inhibitors
L01X: OTHER ANTINEOPLASTIC AGENTS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 421.3
Logarithm of the Partition Coefficient (xlogp) 3.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Bioavailability
The bioavailability of drug is 31.8% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.01 mL/min/kg [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 12 days [4]
Metabolism
The drug is not metabolised []
Unbound Fraction
The unbound fraction of drug in plasma is 0.01% [4]
Vd
The volume of distribution (Vd) of drug is 16.4-26.6 L []
Chemical Identifiers
Formula
C19H14Cl2N2O3S
IUPAC Name
2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
Canonical SMILES
CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl
InChI
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)
InChIKey
BPQMGSKTAYIVFO-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
24776445
ChEBI ID
CHEMBL473417
CAS Number
879085-55-9
UNII
25X868M3DS
DrugBank ID
DB08828
TTD ID
D03EDQ
VARIDT ID
DR00234
INTEDE ID
DR1698
ACDINA ID
D00730
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Smoothened homolog (SMO) TT8J1S3 SMO_HUMAN Modulator [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2C9 (CYP2C9)
Main DME 		DE5IED8 CP2C9_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Protein patched homolog 1 (PTCH1) OTMG07H5 PTC1_HUMAN Gene/Protein Processing [7]
Protein patched homolog 2 (PTCH2) OTOQ0K9V PTC2_HUMAN Gene/Protein Processing [7]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Gene/Protein Processing [7]
Suppressor of fused homolog (SUFU) OT0IRYG1 SUFU_HUMAN Drug Response [8]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Gene/Protein Processing [7]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Gene/Protein Processing [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Gene/Protein Processing [7]
Zinc finger protein GLI2 (GLI2) OTIRV97L GLI2_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Basal cell carcinoma
ICD Disease Classification 2C32
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Smoothened homolog (SMO) DTT SMO 4.01E-06 -0.18 -0.35
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 4.91E-03 -1.59E-01 -3.84E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.29E-36 -3.75E-01 -1.06E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Vismodegib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Tucatinib DMBESUA Moderate Decreased metabolism of Vismodegib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [9]
SODIUM CITRATE DMHPD2Y Minor Decreased absorption of Vismodegib due to altered gastric pH caused by SODIUM CITRATE. Discovery agent [N.A.] [10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Eisenoxyd E00585 56841934 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Vismodegib 150 mg capsule 150 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6975).
2 A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma. J Am Acad Dermatol. 2015 Jul;73(1):99-105.e1.
3 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
6 The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7.
7 Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One. 2011;6(11):e27306. doi: 10.1371/journal.pone.0027306. Epub 2011 Nov 8.
8 Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014 Jul;20(7):732-40. doi: 10.1038/nm.3613. Epub 2014 Jun 29.
9 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
10 Cerner Multum, Inc. "Australian Product Information.".