vismodegib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
SMO receptor antagonists	4227	879085-55-9

Description:

Molecule

Description

Molfile Inchi Smiles

Synonyms:

erivedge
vismodegib
GDC-0449
RG3616

inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity

Molecular weight: 421.29
Formula: C19H14Cl2N2O3S
CLOGP: 2.74
LIPINSKI: 0
HAC: 5
HDO: 1
TPSA: 76.13
ALOGS: -5.39
ROTB: 4

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	4	Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution)	0.23 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.01 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.01 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	245 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 12, 2013	EMA	Roche Registration Ltd
Jan. 30, 2012	FDA	GENENTECH

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Muscle spasms	450.94	34.57	192	2554	122921	46560395
Alopecia	409.13	34.57	195	2551	162219	46521097
Dysgeusia	367.24	34.57	123	2623	40368	46642948
Ageusia	289.51	34.57	77	2669	11395	46671921
Weight decreased	114.16	34.57	96	2650	210753	46472563
Decreased appetite	106.40	34.57	89	2657	193747	46489569
Death	105.53	34.57	113	2633	335435	46347881
Squamous cell carcinoma	59.74	34.57	21	2725	7815	46675501
Fatigue	56.17	34.57	115	2631	608582	46074734
Basal cell carcinoma	52.12	34.57	25	2721	20462	46662854
Nausea	36.41	34.57	105	2641	687349	45995967

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Muscle spasms	964.38	34.51	348	3613	64490	29884027
Alopecia	760.36	34.51	218	3743	19057	29929460
Ageusia	619.54	34.51	158	3803	8795	29939722
Dysgeusia	516.00	34.51	172	3789	24629	29923888
Weight decreased	180.86	34.51	153	3808	150768	29797749
Squamous cell carcinoma	161.63	34.51	58	3903	10192	29938325
Decreased appetite	117.18	34.51	120	3841	149790	29798727
Basal cell carcinoma	91.69	34.51	44	3917	16024	29932493
Death	80.33	34.51	157	3804	357126	29591391
Fatigue	77.03	34.51	145	3816	320528	29627989
Taste disorder	55.93	34.51	20	3941	3463	29945054
Madarosis	48.26	34.51	10	3951	214	29948303
Constipation	47.35	34.51	66	3895	112840	29835677
Myalgia	40.12	34.51	50	3911	76617	29871900
Hypogeusia	39.65	34.51	11	3950	831	29947686
Nausea	37.10	34.51	104	3857	296853	29651664

Pharmacologic Action:

Source	Code	Description
ATC	L01XJ01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Hedgehog pathway inhibitors
FDA MoA	N0000184148	Smoothened Receptor Antagonists
FDA EPC	N0000184149	Hedgehog Pathway Inhibitor
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:50905	teratogen
CHEBI has role	CHEBI:66908	smoothened antagonist
CHEBI has role	CHEBI:140921	hedgehog pathway inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Basal cell carcinoma of skin	indication	254701007

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.07	acidic
pKa2	4.25	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Smoothened homolog	GPCR	Q99835	SMO_HUMAN	INHIBITOR	Ki	7.79		CHEMBL	CHEMBL
Sonic hedgehog protein	Enzyme	Q15465	SHH_HUMAN		IC50	7.82		CHEMBL
Sonic hedgehog protein	Enzyme		SHH_MOUSE		IC50	8.52		CHEMBL
Smoothened homolog	GPCR		SMO_MOUSE		IC50	8.30		CHEMBL

External reference:

ID	Source
D09992	KEGG_DRUG
4031330	VANDF
C3265872	UMLSCUI
CHEBI:66903	CHEBI
VIS	PDB_CHEM_ID
CHEMBL473417	ChEMBL_ID
C538724	MESH_SUPPLEMENTAL_RECORD_UI
24776445	PUBCHEM_CID
9311	INN_ID
25X868M3DS	UNII
6975	IUPHAR_LIGAND_ID
DB08828	DRUGBANK_ID
1242987	RXNORM
187095	MMSL
28293	MMSL
d07824	MMSL
014152	NDDF
703812008	SNOMEDCT_US
703813003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ERIVEDGE	HUMAN PRESCRIPTION DRUG LABEL	1	50242-140	CAPSULE	150 mg	ORAL	NDA	31 sections