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Compound Detail

CHEMBL1229517

VEMURAFENIB
💊 Approved Drug
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💊 Approved Drug
CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(Cl)cc4)cc23)c1F

Basic Information

ChEMBL ID CHEMBL1229517
Name VEMURAFENIB
Phase Approved
Structure Type MOL
InChI Key GPXBXXGIAQBQNI-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

PLX-4032 PLX4032 RG 7204 RG-7204 RO 5185426 RO-51-85426 RO-5185426 Vemurafenib Zelboraf
42
Targets
191
Activities
3
Assay Types
1
PK Parameters
20
Publications
9
Known Names
20
Indications
1
Mechanisms

Molecular Properties

489.9
MW (Da)
5.54
ALogP
4
HBA
2
HBD
91.9
PSA (Ų)
0.33
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2011
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

First in Class
USAN Stem -rafenib
USAN Year 2010

Extended Properties

Molecular Formula C23H18ClF2N3O3S
MW 489.93
Aromatic Rings 4
Heavy Atoms 33
NP-Likeness -1.38

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase B-raf inhibitor INHIBITOR Serine/threonine-protein kinase B-raf

Indications

Melanoma Melanoma Melanoma Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Colorectal Neoplasms Colorectal Neoplasms Craniopharyngioma Hematologic Neoplasms Histiocytosis Histiocytosis, Langerhans-Cell Leukemia, Hairy Cell Leukemia, Myeloid, Acute Multiple Myeloma Pancreatic Neoplasms Thyroid Neoplasms Thyroid Neoplasms Lymphoma

ATC Classification

L01EC01
vemurafenib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 165 meas. best 8.68
Kd 16 meas. best 8.09
EC50 10 meas. best 6.62

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase A-Raf
CHEMBL1169596
IC50 8.68 7.3325 2.1 4
Serine/threonine-protein kinase B-raf
CHEMBL5145
IC50 8.49 7.3005 3.2 64
Mitogen-activated protein kinase kinase kinase 20
CHEMBL3886
IC50 8.4 7.8467 4.0 3
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 8.32 8.32 4.8 1
Dual specificity mitogen-activated protein kinase kinase 4
CHEMBL2201
Kd 8.09 8.09 8.2 1
Serine/threonine-protein kinase B-raf
CHEMBL5145
Kd 8.0 7.0 10.0 4
Activated CDC42 kinase 1
CHEMBL4599
IC50 7.72 7.72 19.0 2
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.62 6.5955 24.0 22
Serine/threonine-protein kinase B-raf
CHEMBL2331061
IC50 7.52 7.52 30.0 1
Unchecked
CHEMBL612545
IC50 7.52 6.43 30.0 10
RAF proto-oncogene serine/threonine-protein kinase
CHEMBL1906
IC50 7.32 6.6578 48.0 9
Epidermal growth factor receptor
CHEMBL203
IC50 7.32 7.32 48.0 1
HT-29
CHEMBL384
IC50 7.31 6.488 49.0 5
A-375
CHEMBL613859
IC50 7.1 6.474 79.0 15
C32
CHEMBL1075401
IC50 7.08 7.08 84.0 1
M14
CHEMBL614317
IC50 7.06 6.43 88.0 3
SK-MEL-28
CHEMBL614919
IC50 7.0 6.58 100.0 3
Serine/threonine-protein kinase Nek11
CHEMBL5638
Kd 6.72 6.72 190.0 1
COLO 205
CHEMBL614561
EC50 6.62 6.62 240.0 1
Mitogen-activated protein kinase kinase kinase 20
CHEMBL3886
Kd 6.5 6.5 316.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 6.44 6.44 360.0 1
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 6.37 6.37 427.0 1
BRAF/CRAF
CHEMBL4106189
EC50 6.22 6.22 601.0 1
Dual specificity mitogen-activated protein kinase kinase 5
CHEMBL4948
Kd 6.13 6.13 734.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
EC50 6.1 5.95 790.0 2
Serine/threonine-protein kinase B-raf
CHEMBL5145
EC50 6.1 5.87 794.3 2
Ferrochelatase, mitochondrial
CHEMBL3879831
Kd 5.85 5.85 1419.0 1
Protein-tyrosine kinase 6
CHEMBL4601
Kd 5.85 5.85 1411.0 1
SK-MEL-1
CHEMBL614916
IC50 5.82 5.82 1499.0 1
Dual specificity mitogen-activated protein kinase kinase; MEK1/2
CHEMBL2111289
IC50 5.82 5.82 1500.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
EC50 5.8 5.8 1600.0 1
Mitogen-activated protein kinase kinase kinase kinase 5
CHEMBL4852
Kd 5.75 5.75 1800.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
Kd 5.68 5.68 2079.0 1
Serine/threonine-protein kinase A-Raf
CHEMBL1169596
Kd 5.67 5.67 2138.0 1
UACC-903
CHEMBL612446
IC50 5.57 5.3067 2700.0 3
8505C
CHEMBL1075387
IC50 5.53 5.53 2940.0 1
TGF-beta receptor type-2
CHEMBL4267
Kd 5.47 5.47 3396.0 1
L929
CHEMBL612267
EC50 5.43 5.43 3750.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
EC50 5.4 5.4 4000.0 1
Ferrochelatase, mitochondrial
CHEMBL3879831
EC50 5.3 5.3 5011.9 1
Serine/threonine-protein kinase Nek2
CHEMBL3835
Kd 5.3 5.3 5000.0 1
COLO 205
CHEMBL614561
IC50 5.29 5.29 5160.0 1
HepG2
CHEMBL395
IC50 5.26 5.26 5480.0 2
SK-MEL-2
CHEMBL614917
IC50 5.25 5.25 5600.0 2
A2058
CHEMBL613503
IC50 5.06 5.06 8700.0 1
Aspartyl/asparaginyl beta-hydroxylase
CHEMBL4680030
IC50 4.98 4.865 10500.0 4
CHL-1
CHEMBL1075422
IC50 4.9 4.82 12700.0 3
GTPase KRas
CHEMBL2189121
IC50 4.78 4.78 16600.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 6.61 uL.min-1.(10^6cells)-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase A-Raf IC50 = 2.1 nM 8.68 Inhibition of ARAF (unknown origin) using human His6-tagged MEK1 K97R mutant as ... 28242553
Serine/threonine-protein kinase A-Raf IC50 = 2.1 nM 8.68 Inhibition of ARaf (unknown origin) 30529543
Serine/threonine-protein kinase B-raf IC50 = 3.2 nM 8.49 Inhibition of BRAF V600E mutant (unknown origin) 23623674
Serine/threonine-protein kinase B-raf IC50 = 4.0 nM 8.4 Inhibition of B-Raf V600E mutant (unknown origin) assessed as MEK1 phosphorylati... 27085672
Mitogen-activated protein kinase kinase kinase 20 IC50 = 4.0 nM 8.4 Inhibition of full-length human ZAK using MBP as substrate in presence off ATP b... 37094449
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 4.8 nM 8.32 Inhibition of RET (unknown origin) 38852338
Serine/threonine-protein kinase B-raf IC50 = 6.1 nM 8.21 Inhibition of recombinant BRAF V600E mutant (unknown origin) assessed as ADP for... 25965804
Serine/threonine-protein kinase B-raf IC50 = 6.9 nM 8.16 Inhibition of wild-type BRAF (unknown origin) using human His6-tagged MEK1 K97R ... 28242553
Serine/threonine-protein kinase B-raf IC50 = 6.9 nM 8.16 Inhibition of BRAF (unknown origin) 30529543
Dual specificity mitogen-activated protein kinase kinase 4 Kd = 8.2 nM 8.09 Binding affinity to GST tagged mouse MKK4 expressed in Escherichia coli expressi... 33199152
Serine/threonine-protein kinase B-raf IC50 = 9.6 nM 8.02 Inhibition of human recombinant BRAF V600E mutant using MEK1 as substrate measur... 31252305
Serine/threonine-protein kinase B-raf Kd = 10.0 nM 8.0 Binding affinity to BRAF V600E mutant in human WM278 cells by KINOMEscann Kinase... 37182332
Serine/threonine-protein kinase B-raf IC50 = 13.0 nM 7.89 Inhibition of B-Raf V600E mutant (448 to 723 residues) (unknown origin) expresse... 34591474
Serine/threonine-protein kinase B-raf IC50 = 13.0 nM 7.89 Inhibition of wild type N-terminal 6His-tagged BRAF V600E mutant (unknown origin... 36155354
Serine/threonine-protein kinase B-raf IC50 = 17.0 nM 7.77 Inhibition of B-Raf V600E mutant in human A375 cells assessed as ERK phosphoryla... 27085672
Activated CDC42 kinase 1 IC50 = 19.0 nM 7.72 Inhibition of ACK1 (unknown origin) 34735773
Activated CDC42 kinase 1 IC50 = 19.0 nM 7.72 Inhibition of ACK1 (unknown origin) 37134203
Serine/threonine-protein kinase B-raf IC50 = 20.0 nM 7.7 Inhibition of wild type B-Raf (unknown origin) assessed as MEK1 phosphorylation ... 27085672
Serine/threonine-protein kinase B-raf IC50 = 21.0 nM 7.68 Inhibition of BRAF V600E mutant (unknown origin) after 20 mins by immunoblotting... 29407977
Serine/threonine-protein kinase B-raf IC50 = 21.0 nM 7.68 Inhibition of wild type BRAF (unknown origin) 23623674

Literature References

PubMed DOI Target Context # Activities
31327679 10.1016/j.bmc.2019.07.007 MCF7 24
37182332 10.1016/j.ejmech.2023.115446 Serine/threonine-protein kinase B-raf 7
24471466 10.1021/jm4019542 NON-PROTEIN TARGET 6
25101911 10.1021/jm501177w HepG2 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
28458134 10.1016/j.ejmech.2017.04.052 Unchecked 6
29191878 10.1126/science.aan4368 Unchecked 5
33069066 10.1016/j.bmc.2020.115675 Aspartyl/asparaginyl beta-hydroxylase 5
26005530 10.1021/acsmedchemlett.5b00039 NON-PROTEIN TARGET 5
27085672 10.1016/j.bmc.2016.03.055 Serine/threonine-protein kinase B-raf 5
36878151 10.1016/j.ejmech.2023.115231 Unchecked 4
25915038 10.1371/journal.pone.0125028 A-375 4
27634195 10.1016/j.bmcl.2016.09.003 NON-PROTEIN TARGET 4
25915038 10.1371/journal.pone.0125028 M14 4
29407977 10.1016/j.ejmech.2018.01.053 Serine/threonine-protein kinase B-raf 4
25965804 10.1021/acs.jmedchem.5b00067 Serine/threonine-protein kinase B-raf 4
25462267 10.1016/j.ejmech.2014.10.039 Serine/threonine-protein kinase B-raf 4
30529543 10.1016/j.ejmech.2018.11.033 Serine/threonine-protein kinase B-raf 4
31312411 10.1021/acsmedchemlett.9b00194 Serine/threonine-protein kinase B-raf 3
30108894 10.1039/C7MD00229G Serine/threonine-protein kinase B-raf 3

Data from ChEMBL 36 via Core Engine