vismodegib 🐶 Veterinary Use | 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
S (Water solubility)	0.00 mg/mL	Bocci G, Oprea TI, Benet LZ

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	517.23	36.89	213	2796	155937	63330076
Dysgeusia	416.82	36.89	133	2876	46577	63439436
Alopecia	387.88	36.89	223	2786	337313	63148700
Ageusia	335.91	36.89	86	2923	13642	63472371
Death	163.18	36.89	137	2872	374244	63111769
Weight decreased	127.94	36.89	105	2904	276693	63209320
Decreased appetite	117.53	36.89	96	2913	250956	63235057
Squamous cell carcinoma	66.15	36.89	22	2987	8610	63477403
Fatigue	46.72	36.89	118	2891	887910	62598103
No adverse event	43.24	36.89	26	2983	41379	63444634
Nausea	40.22	36.89	109	2900	854362	62631651

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	1092.43	33.13	393	4081	74608	34877849
Alopecia	829.63	33.13	244	4230	24111	34928346
Ageusia	690.01	33.13	176	4298	10132	34942325
Dysgeusia	553.91	33.13	183	4291	26314	34926143
Weight decreased	208.68	33.13	175	4299	176126	34776331
Squamous cell carcinoma	157.04	33.13	58	4416	11417	34941040
Decreased appetite	135.20	33.13	134	4340	166258	34786199
Death	117.32	33.13	193	4281	397856	34554601
Fatigue	78.49	33.13	156	4318	370497	34581960
Taste disorder	68.76	33.13	28	4446	7127	34945330
Myalgia	50.70	33.13	58	4416	84052	34868405
No adverse event	49.90	33.13	33	4441	22894	34929563
Madarosis	48.02	33.13	10	4464	227	34952230
Constipation	46.16	33.13	71	4403	136911	34815546
Nausea	38.92	33.13	113	4361	339795	34612662
Hypogeusia	38.59	33.13	11	4463	948	34951509

FDA Adverse Event Reporting System (Geriatric)

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	932.72	31.60	366	4763	174364	79564895
Dysgeusia	566.62	31.60	190	4939	56987	79682272
Ageusia	545.36	31.60	140	4989	16492	79722767
Alopecia	455.75	31.60	243	4886	231112	79508147
Weight decreased	188.09	31.60	166	4963	355032	79384227
Death	183.12	31.60	202	4927	566312	79172947
Decreased appetite	173.20	31.60	156	4973	342262	79396997
Squamous cell carcinoma	154.48	31.60	52	5077	15570	79723689
Fatigue	86.45	31.60	186	4943	929541	78809718
Neutrophil count decreased	61.89	31.60	50	5079	93909	79645350
Embolism	52.51	31.60	23	5106	13959	79725300
Myalgia	50.67	31.60	61	5068	185580	79553679
Taste disorder	43.62	31.60	21	5108	15802	79723457
Madarosis	42.82	31.60	13	5116	2789	79736470
Lymphocyte count decreased	37.26	31.60	28	5101	47261	79691998
Nausea	35.53	31.60	138	4991	957058	78782201

FDA Adverse Event Reporting System (Pediatric)

None

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	antineoplastic agents
CHEBI has role	CHEBI:50905	teratogeno
CHEBI has role	CHEBI:66908	SMO receptor antagonists
CHEBI has role	CHEBI:140921	Hedgehog pathway inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Basal cell carcinoma of skin	indication	254701007
Pregnancy, function	contraindication	289908002
Hypericum perforatum extract	contraindication	412515006
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
150MG	ERIVEDGE	GENENTECH	N203388	Jan. 30, 2012	RX	CAPSULE	ORAL	9790183	Sept. 2, 2025	METHOD OF USING VISMODEGIB TO TREAT BASAL CELL CARCINOMA
150MG	ERIVEDGE	GENENTECH	N203388	Jan. 30, 2012	RX	CAPSULE	ORAL	9278961	Dec. 15, 2028	METHOD OF USING VISMODEGIB TO TREAT CANCER IN A MAMMAL

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
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	5.85		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
CHEBI:66903	CHEBI
VIS	PDB_CHEM_ID
CHEMBL473417	ChEMBL_ID
C538724	MESH_SUPPLEMENTAL_RECORD_UI
6975	IUPHAR_LIGAND_ID
9311	INN_ID
DB08828	DRUGBANK_ID
25X868M3DS	UNII
1242987	RXNORM
187095	MMSL
28293	MMSL
d07824	MMSL
014152	NDDF
703812008	SNOMEDCT_US
703813003	SNOMEDCT_US
C2987716	UMLSCUI
24776445	PUBCHEM_CID

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
ERIVEDGE	HUMAN PRESCRIPTION DRUG LABEL	1	50242-140	CAPSULE	150 mg	ORAL	NDA	31 sections