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]
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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: CHEBI:66903
CAS Number: 879085-55-9
DrugBank ID: DB08828
TTD ID: D03EDQ
VARIDT ID: DR00234
INTEDE ID: DR1698
ACDINA ID: D00730

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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]

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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]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[7]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Drug Response	[8]
Platelet-derived growth factor receptor alpha (PDGFRA)	OTDJXUCN	PGFRA_HUMAN	Gene/Protein Processing	[7]
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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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)

MEA Detail

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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]
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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
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Vismodegib 150 mg capsule	150 mg	Oral Capsule	Oral

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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.".