Compound Detail

CHEMBL473417

VISMODEGIB

💊 Approved Drug

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💊 Approved Drug

CS(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL473417
Name	VISMODEGIB
Phase	Approved
Structure Type	MOL
InChI Key	BPQMGSKTAYIVFO-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Erivedge GDC-0449 NSC-747691 NSC-755986 Vismodegib

130

Targets

676

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

421.3

MW (Da)

4.71

ALogP

HBA

HBD

76.1

PSA (Å²)

0.66

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2012
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product First in Class

USAN Stem	-degib
USAN Year	2009

Extended Properties

Molecular Formula	C19H14Cl2N2O3S
MW	421.31
Aromatic Rings	3
Heavy Atoms	27
NP-Likeness	-2.12

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Smoothened homolog inhibitor	INHIBITOR	Protein smoothened	✓	✓

Indications

Carcinoma, Basal Cell Carcinoma, Basal Cell Neoplasms Neoplasms Basal Cell Nevus Syndrome Breast Neoplasms Breast Neoplasms Bronchiolitis Obliterans Syndrome Carcinoma, Pancreatic Ductal Chondrosarcoma, Clear Cell Chondrosarcoma, Mesenchymal Glioblastoma Glioblastoma Gliosarcoma Idiopathic Pulmonary Fibrosis Leukemia, Myeloid, Acute Medulloblastoma Medulloblastoma Meningioma Multiple Myeloma

ATC Classification

L01XJ01

vismodegib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Drug Warnings

Black Box Warning

teratogenicity

Country: United States

Activity Summary

IC50 653 meas. best 9.4

Kd 15 meas. best 7.01

EC50 6 meas. best 8.7

Ki 2 meas. best 7.91

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Protein smoothened CHEMBL5971	IC50	9.4	8.004	0.4	10
Protein smoothened CHEMBL6080	IC50	8.82	7.7038	1.5	8
Protein smoothened CHEMBL5971	EC50	8.7	8.61	2.0	2
Protein smoothened CHEMBL6080	EC50	8.7	8.515	2.0	2
Unchecked CHEMBL612545	IC50	8.7	6.8076	2.0	29
Molecular identity unknown CHEMBL612546	IC50	8.64	7.736	2.3	10
Sonic hedgehog protein CHEMBL5387	IC50	8.52	8.042	3.0	5
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.4	5.8286	4.0	7
Medulloblastoma cell CHEMBL4296520	IC50	8.33	7.925	4.7	2
C3H 10T1/2 CHEMBL614531	IC50	7.96	7.96	11.0	1
Protein smoothened CHEMBL5971	Ki	7.91	7.85	12.2	2
Molecular identity unknown CHEMBL612546	EC50	7.89	7.89	13.0	1
Sonic hedgehog protein CHEMBL5602	IC50	7.82	6.79	15.0	2
IGROV-1 CHEMBL613984	IC50	7.14	7.14	72.5	1
Protein smoothened CHEMBL5971	Kd	7.01	7.01	97.5	1
HT-29 CHEMBL384	IC50	5.97	5.275	1080.0	2
ADMET CHEMBL612558	Kd	5.96	5.525	1100.0	4
HCE-T CHEMBL2366139	IC50	5.88	5.88	1322.5	1
Broad substrate specificity ATP-binding cassette transporter ABCG2 CHEMBL5393	IC50	5.85	5.85	1400.0	1
D-542MG CHEMBL2366208	IC50	5.73	5.73	1867.4	1
23132-87 CHEMBL1075382	IC50	5.36	5.36	4401.5	1
Ubiquitin carboxyl-terminal hydrolase 28 CHEMBL2157853	IC50	5.36	5.34	4410.0	2
Albumin CHEMBL3253	Kd	5.26	5.24	5500.0	2
Albumin CHEMBL4817	Kd	5.24	5.24	5800.0	1
HDLM-2 CHEMBL2366231	IC50	5.09	5.09	8047.7	1
ACN CHEMBL2366195	IC50	5.07	5.07	8501.1	1
HuO-3N1 CHEMBL1075475	IC50	5.02	5.02	9601.1	1
BHT-101 CHEMBL1075398	IC50	4.94	4.94	11380.0	1
KYSE-150 cell line CHEMBL613998	IC50	4.94	4.94	11584.1	1
MC-IXC CHEMBL1075495	IC50	4.91	4.91	12229.2	1
D-423MG CHEMBL2366134	IC50	4.89	4.89	12765.7	1
NY CHEMBL1075552	IC50	4.83	4.83	14890.3	1
NB7 CHEMBL2366345	IC50	4.8	4.8	15891.0	1
HOS CHEMBL614736	IC50	4.8	4.8	15671.9	1
DMS-273 CHEMBL614034	IC50	4.78	4.78	16671.3	1
MDA-MB-361 CHEMBL614129	IC50	4.76	4.76	17271.1	1
DU-145 CHEMBL613508	IC50	4.74	4.74	18320.0	1
NCI-H82 CHEMBL2366077	IC50	4.7	4.7	19838.6	1
SNU1 CHEMBL614931	IC50	4.7	4.7	20019.6	1
GCT CHEMBL1075448	IC50	4.68	4.68	20882.4	1
C2BBe1 CHEMBL2366283	IC50	4.68	4.68	21105.8	1
LB2241-RCC CHEMBL2366330	IC50	4.66	4.66	21844.1	1
COLO-829 CHEMBL2366275	IC50	4.65	4.65	22187.1	1
EW-11 CHEMBL2366223	IC50	4.64	4.64	22802.2	1
NCI-H526 CHEMBL2366102	IC50	4.63	4.63	23471.7	1
SF-295 CHEMBL614908	IC50	4.62	4.62	24025.2	1
D-566MG CHEMBL2366336	IC50	4.6	4.6	25294.3	1
8505C CHEMBL1075387	IC50	4.59	4.59	25633.1	1
NBsusSR CHEMBL2366150	IC50	4.57	4.57	26800.6	1
BV-173 CHEMBL2366145	IC50	4.55	4.55	28318.2	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	2455.65	ng.hr.mL-1	Rattus norvegicus
AUC	2500.0	ng.hr.mL-1	Rattus norvegicus
AUC	2456.0	ng.hr.mL-1	Rattus norvegicus
AUC	2455.65	ng.hr.mL-1	Rattus norvegicus
AUC	22403.25	ng.hr.mL-1	Rattus norvegicus
AUC	4049.8	ng.hr.mL-1	Mus musculus
AUC	7657.68	ng.hr.mL-1	Mus musculus
AUC	2456.0	ng.hr.mL-1	Rattus norvegicus
CL	3.7	mL.min-1.kg-1	Rattus norvegicus
CL	0.4	mL.min-1.kg-1	Canis lupus familiaris
CL	3.7	mL.min-1.kg-1	Rattus norvegicus
CL	6.771	mL.min-1.kg-1	Rattus norvegicus
CL	6.8	mL.min-1.kg-1	Rattus norvegicus
CL	6.767	mL.min-1.kg-1	Rattus norvegicus
CL	6.771	mL.min-1.kg-1	Rattus norvegicus
CL	4.681	mL.min-1.kg-1	Rattus norvegicus
CL	6.767	mL.min-1.kg-1	Rattus norvegicus
CL	5.6	mL.min-1.kg-1	Mus musculus
CL	2.0	mL.min-1.kg-1	Rattus norvegicus
CL	0.04	mL.min-1.kg-1	Canis lupus familiaris
CL	19.0	%	Canis lupus familiaris
Cmax	2966.94	nM	Rattus norvegicus
Cmax	2848.26	nM	Rattus norvegicus
Cmax	2966.94	nM	Rattus norvegicus
Cmax	2966.94	nM	Rattus norvegicus
Cmax	8637.35	nM	Rattus norvegicus
Cmax	2027.01	nM	Mus musculus
Cmax	2966.94	nM	Rattus norvegicus
F	100.0	%	Rattus norvegicus
F	33.0	%	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Protein smoothened	IC50	=	0.4	nM	9.4	Inhibition of SMO-mediated hedgehog signalling pathway in human HPEM cells by lu...	31862310
Protein smoothened	IC50	=	1.5	nM	8.82	Antagonist activity at Smo in mouse Shh-Light 2 cells assessed as inhibition of ...	23063522
Protein smoothened	EC50	=	2.0	nM	8.7	Displacement of BODIPY-labeled cyclopamine from mouse SMO transfected in human H...	31862310
Protein smoothened	EC50	=	2.0	nM	8.7	Binding affinity to human SMO	31862310
Unchecked	IC50	=	2.0	nM	8.7	Inhibition of GLI in mouse ASZ001 cells assessed as reduction in cell viability ...	35859880
Unchecked	IC50	=	2.3	nM	8.64	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 Light2 cells by Gli-lu...	28688278
Molecular identity unknown	IC50	=	2.3	nM	8.64	Inhibition of hedgehog signaling (unknown origin) expressed in mouse NIH/3T3 cel...	27180012
Unchecked	IC50	=	2.46	nM	8.61	Inhibition of hedgehog signaling pathway in mouse Light2 cells after 48 hrs by G...	29739714
Protein smoothened	EC50	=	3.0	nM	8.52	Displacement of BODIPY-labeled cyclopamine from human SMO transfected in human H...	31862310
Sonic hedgehog protein	IC50	=	3.0	nM	8.52	Inhibition of SHH in mouse Shh Light2 cells by GLI-responsive firefly luciferase...	19309080
NON-PROTEIN TARGET	IC50	=	4.0	nM	8.4	Antiproliferative activity against SAG-induced rat cerebellar granule cell precu...	22268551
Medulloblastoma cell	IC50	=	4.7	nM	8.33	Antiproliferative activity against mouse Ptch+/- medulloblastoma cells assessed ...	30939349
Protein smoothened	EC50	=	4.7	nM	8.33	Inhibition of SMO-mediated Hedgehog signaling pathway in mouse C3H10T1/2 cells a...	31862310
Protein smoothened	IC50	=	5.0	nM	8.3	Inhibition of Smo in mouse C3H10T1/2 cells using human recombinant SHH assessed ...	24900436
Unchecked	IC50	=	5.0	nM	8.3	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells measured after 2...	27810591
Protein smoothened	IC50	=	5.1	nM	8.29	Displacement of BODIPY-cyclopamine from human Smo expressed in HEK293 cells incu...	-
Protein smoothened	IC50	=	6.0	nM	8.22	Displacement of boron-dipyrromethene-cyclopamine from human smoothened receptor ...	-
Protein smoothened	IC50	=	6.0	nM	8.22	Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3 cells expr...	29499483
Protein smoothened	IC50	=	7.0	nM	8.15	Displacement of BODIPY-labelled cyclopamine from human Smo receptor expressed in...	22268551
Unchecked	IC50	=	7.0	nM	8.15	Inhibition of hedgehog signalling pathway in mouse NIH3T3 cells by Gli-Bla repor...	36332550

Literature References

PubMed	DOI	Target Context	# Activities
21438527	10.1021/jm1008924	ADMET	17
31862310	10.1016/j.bmc.2019.115227	ADMET	15
26820554	10.1016/j.ejmech.2016.01.018	Rattus norvegicus	13
28873303	10.1021/acs.jmedchem.7b01185	Unchecked	12
-	10.6019/CHEMBL5058564	HEK-293T	9
26254279	10.18632/oncotarget.4214	Unchecked	9
-	10.6019/CHEMBL5058564	Fibroblast	8
24973920	10.1038/nm.3613	Medulloblastoma cell	7
21438527	10.1021/jm1008924	Albumin	7
32690258	10.1016/j.bmc.2020.115584	ADMET	7
31862310	10.1016/j.bmc.2019.115227	Protein smoothened	6
24486203	10.1016/j.bmc.2013.12.055	Rattus norvegicus	6
27810591	10.1016/j.ejmech.2016.10.040	Unchecked	6
35859880	10.1021/acsmedchemlett.1c00562	Unchecked	6
24405704	10.1016/j.bmcl.2013.12.050	Rattus norvegicus	6
26827136	10.1016/j.bmc.2016.01.034	Rattus norvegicus	6
24900716	10.1021/ml400014t	Molecular identity unknown	6
-	10.6019/CHEMBL5058564	U2OS	6
30471551	10.1016/j.ejmech.2018.11.028	Unchecked	5
29929879	10.1016/j.bmcl.2018.06.025	Mus musculus	5

Data from ChEMBL 36 via Core Engine