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Compound Detail

CHEMBL2146883

COBIMETINIB
💊 Approved Drug
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💊 Approved Drug
O=C(c1ccc(F)c(F)c1Nc1ccc(I)cc1F)N1CC(O)([C@@H]2CCCCN2)C1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL2146883
Name COBIMETINIB
Phase Approved
Structure Type MOL
InChI Key BSMCAPRUBJMWDF-KRWDZBQOSA-N
Therapeutic ✓ Yes

Known Names

Cobimetinib Gdc 0623 Gdc 0973 Gdc-0623 GDC-0973 RG 7420 RG-7420 RG7420 Xl 518 Xl518
8
Targets
18
Activities
2
Assay Types
30
PK Parameters
20
Publications
10
Known Names
20
Indications
2
Mechanisms

Molecular Properties

531.3
MW (Da)
3.78
ALogP
4
HBA
3
HBD
64.6
PSA (Ų)
0.53
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2015
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2012

Extended Properties

Molecular Formula C21H21F3IN3O2
MW 531.32
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -0.86

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor INHIBITOR Dual specificity mitogen-activated protein kinase kinase 1 ✓ ✓
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor INHIBITOR Dual specificity mitogen-activated protein kinase kinase 2 ✓ ✓

Indications

Neoplasms Neoplasms Colorectal Neoplasms Colorectal Neoplasms Melanoma Melanoma Melanoma Breast Neoplasms Breast Neoplasms Carcinoma, Non-Small-Cell Lung Craniopharyngioma Gallbladder Neoplasms Hematologic Neoplasms Intracranial Arteriovenous Malformations Leukemia, Myelomonocytic, Chronic Thyroid Neoplasms Adenocarcinoma Esophageal Neoplasms Leukemia, Myeloid, Acute Multiple Myeloma

ATC Classification

L01EE02
cobimetinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 15 meas. best 9.7
Kd 3 meas. best 7.66

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Dual specificity mitogen-activated protein kinase kinase; MEK1/2
CHEMBL2111289
 IC50 9.7 9.7 0.2 1
Dual specificity mitogen-activated protein kinase kinase 1
CHEMBL3587
 IC50 9.05 8.4471 0.9 7
Serine/threonine-protein kinase B-raf
CHEMBL5145
 IC50 8.74 8.74 1.8 1
A-375
CHEMBL613859
 IC50 8.3 8.3 5.0 1
NON-PROTEIN TARGET
CHEMBL3879801
 IC50 8.1 8.1 8.0 1
Dual specificity mitogen-activated protein kinase kinase 2
CHEMBL2964
 Kd 7.66 7.66 22.0 1
Dual specificity mitogen-activated protein kinase kinase 2
CHEMBL2964
 IC50 7.64 7.64 23.0 1
Actin-related protein 3
CHEMBL4105857
 Kd 7.44 7.44 36.0 1
Actin-related protein 3
CHEMBL4105857
 IC50 7.28 7.28 53.0 1
IMR-32
CHEMBL614585
 IC50 7.16 7.16 70.0 1
Dual specificity mitogen-activated protein kinase kinase 1
CHEMBL3587
 Kd 6.51 6.51 309.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 0.64 ng.hr.mL-1 Macaca fascicularis
AUC 3.34 ng.hr.mL-1 Macaca fascicularis
AUC 11.9 ng.hr.mL-1 Canis lupus familiaris
AUC 17.1 ng.hr.mL-1 Canis lupus familiaris
AUC 1.59 ng.hr.mL-1 Rattus norvegicus
AUC 2.32 ng.hr.mL-1 Rattus norvegicus
AUC 1.51 ng.hr.mL-1 Mus musculus
AUC 0.935 ng.hr.mL-1 Mus musculus
CL 59.42 mL.min-1.kg-1 Rattus norvegicus
CL 29.6 mL.min-1.kg-1 Macaca fascicularis
CL 5.53 mL.min-1.kg-1 Canis lupus familiaris
CL 37.8 mL.min-1.kg-1 Rattus norvegicus
CL 33.5 mL.min-1.kg-1 Mus musculus
Cmax 0.09411 nM Macaca fascicularis
Cmax 1.587 nM Canis lupus familiaris
Cmax 0.3632 nM Rattus norvegicus
Cmax 0.3463 nM Mus musculus
F 77.0 % Rattus norvegicus
F 19.6 % Macaca fascicularis
F 69.1 % Canis lupus familiaris
F 69.0 % Rattus norvegicus
F 53.9 % Mus musculus
Fu 0.0012 - Mus musculus
T1/2 6.1 hr Rattus norvegicus
T1/2 10.3 hr Macaca fascicularis
T1/2 9.19 hr Canis lupus familiaris
T1/2 13.3 hr Rattus norvegicus
T1/2 3.92 hr Mus musculus
Tmax 2.0 hr Macaca fascicularis
Tmax 2.67 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 IC50 = 0.2 nM 9.7 Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T ce... 24900486
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.9 nM 9.05 Inhibition of MEK1-mediated ERK2 T202/Y204 phosphorylation using biotinylated MB... 24900486
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.9 nM 9.05 Inhibition of MEK1 (unknown origin) by biochemical assay 37657268
Serine/threonine-protein kinase B-raf IC50 = 1.8 nM 8.74 Inhibition of B-raf V600E mutant in human COLO205 cells assessed as reduction of... 22315332
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 4.2 nM 8.38 Inhibition of MEK1 (unknown origin) 22315332
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 4.2 nM 8.38 Affinity Biochemical interaction (Enzymatic inhibition assay) EUB0000684a MAP2K1 -
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 4.2 nM 8.38 Inhibition of MEK1 (unknown origin) 36924668
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 4.2 nM 8.38 Inhibition of MEK1 (unknown origin) 22084396
A-375 IC50 = 5.0 nM 8.3 Antiproliferative activity against human A375 cells assessed as reduction in cel... 31804822
NON-PROTEIN TARGET IC50 = 8.0 nM 8.1 Antiproliferative activity against human COLO205 cells expressing B-raf V600E mu... 22315332
Dual specificity mitogen-activated protein kinase kinase 2 Kd = 22.0 nM 7.66 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 23.0 nM 7.64 Selectivity interaction (Kinase panel (enzymatic assay)) EUB0000684a MAP2K2 -
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 31.0 nM 7.51 Selectivity interaction (Kinase panel (enzymatic assay)) EUB0000684a MAP2K1 -
Actin-related protein 3 Kd = 36.0 nM 7.44 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Actin-related protein 3 IC50 = 53.0 nM 7.28 Selectivity interaction (Kinase panel (enzymatic assay)) EUB0000684a ACTR3 -
IMR-32 IC50 = 70.0 nM 7.16 Antiproliferative activity against human IMR-32 cells assessed as cell growth in... 32937281
Dual specificity mitogen-activated protein kinase kinase 1 Kd = 309.0 nM 6.51 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878

Literature References

PubMed DOI Target Context # Activities
22084396 10.1158/0008-5472.can-11-1515 Unchecked 138
22084396 10.1158/0008-5472.can-11-1515 A2058 29
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
22084396 10.1158/0008-5472.can-11-1515 NCI-H2122 11
- 10.6019/CHEMBL4689842 U2OS 10
24900486 10.1021/ml300049d Mus musculus 9
22315332 10.1124/dmd.111.043778 Mus musculus 8
22315332 10.1124/dmd.111.043778 Rattus norvegicus 8
22315332 10.1124/dmd.111.043778 Canis familiaris 8
22315332 10.1124/dmd.111.043778 Cynomolgus monkey 8
22084396 10.1158/0008-5472.can-11-1515 888-mel 8
22084396 10.1158/0008-5472.can-11-1515 DLD-1 8
22315332 10.1124/dmd.111.043778 ADMET 7
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.6019/CHEMBL4689842 HEK-293T 6
24900486 10.1021/ml300049d Plasma 6
22084396 10.1158/0008-5472.can-11-1515 A-375 5
24900486 10.1021/ml300049d Rattus norvegicus 5
24900486 10.1021/ml300049d Brain 5

Data from ChEMBL 36 via Core Engine