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Compound Detail

CHEMBL2103875

TRAMETINIB
💊 Approved Drug
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💊 Approved Drug
CC(=O)Nc1cccc(-n2c(=O)n(C3CC3)c(=O)c3c(Nc4ccc(I)cc4F)n(C)c(=O)c(C)c32)c1

Basic Information

ChEMBL ID CHEMBL2103875
Name TRAMETINIB
Phase Approved
Structure Type MOL
InChI Key LIRYPHYGHXZJBZ-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

GSK-1120212 GSK1120212 JTP 74057 JTP-74057 Mekinist TMT-212 Tmt212 Trametinib
14
Targets
112
Activities
3
Assay Types
4
PK Parameters
20
Publications
8
Known Names
20
Indications
1
Mechanisms

Molecular Properties

615.4
MW (Da)
3.94
ALogP
8
HBA
2
HBD
107.1
PSA (Ų)
0.33
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2013
Availability Unknown
Chirality Achiral
USAN Stem -tinib
USAN Year 2011

Extended Properties

Molecular Formula C26H23FIN5O4
MW 615.40
Aromatic Rings 4
Heavy Atoms 37
NP-Likeness -1.57

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor INHIBITOR Dual specificity mitogen-activated protein kinase kinase; MEK1/2

Indications

Neoplasms Neoplasms Melanoma Melanoma Melanoma Sarcoma Thyroid Neoplasms Thyroid Neoplasms Thyroid Neoplasms Adenocarcinoma, Follicular Ameloblastoma Biliary Tract Neoplasms Breast Neoplasms Breast Neoplasms Carcinoma Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma Colonic Neoplasms Colorectal Neoplasms

ATC Classification

L01EE01
trametinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 107 meas. best 9.32
Kd 3 meas. best 8.52
EC50 2 meas. best 7.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Dual specificity mitogen-activated protein kinase kinase 2
CHEMBL2964
IC50 9.32 8.2344 0.5 16
Dual specificity mitogen-activated protein kinase kinase 1
CHEMBL3587
IC50 9.32 8.2944 0.5 16
A-375
CHEMBL613859
IC50 9.13 9.13 0.7 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 9.0 7.7978 1.0 55
Dual specificity mitogen-activated protein kinase kinase; MEK1/2
CHEMBL2111289
IC50 8.7 6.76 2.0 8
Unchecked
CHEMBL612545
IC50 8.7 8.66 2.0 2
HL-60
CHEMBL383
IC50 8.52 8.52 3.0 1
Unchecked
CHEMBL612545
Kd 8.52 8.52 3.0 1
Dual specificity mitogen-activated protein kinase kinase 2
CHEMBL2964
Kd 8.05 8.05 9.0 1
KYSE-520 cell line
CHEMBL612701
IC50 8.0 8.0 10.0 1
Influenza A virus
CHEMBL613740
EC50 7.8 7.8 16.0 1
MDA-MB-231
CHEMBL400
IC50 7.75 7.75 18.0 1
HCT-116
CHEMBL394
IC50 7.72 6.83 19.0 2
Dual specificity mitogen-activated protein kinase kinase 1
CHEMBL3587
Kd 7.21 7.21 62.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
EC50 6.61 6.61 247.0 1
A549
CHEMBL392
IC50 6.53 5.7633 296.0 3
DLD-1
CHEMBL614285
IC50 5.87 5.87 1340.0 1

Pharmacokinetic Data

Parameter Value Units Species
T1/2 40.0 hr Homo sapiens
T1/2 30.0 hr Rattus norvegicus
T1/2 0.4167 hr Homo sapiens
T1/2 12.4 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.48 nM 9.32 Affinity Phenotypic Cellular interaction: (Cytotoxicity sulforhodamine B assay (... -
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 0.48 nM 9.32 Affinity Phenotypic Cellular interaction: (Cytotoxicity sulforhodamine B assay (... -
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.52 nM 9.28 Affinity Phenotypic Cellular interaction: (Cytotoxicity sulforhodamine B assay (... -
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 0.52 nM 9.28 Affinity Phenotypic Cellular interaction: (Cytotoxicity sulforhodamine B assay (... -
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.7 nM 9.15 Inhibition of MEK1 (unknown origin) 30826508
A-375 IC50 = 0.74 nM 9.13 Antiproliferative activity against human A375 cells assessed as reduction in cel... 31804822
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.92 nM 9.04 Non competitive inhibition of MEK1 (unknown origin) 33539089
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 0.92 nM 9.04 Inhibition of MEK1 (unknown origin) 33539089
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 0.92 nM 9.04 Affinity Biochemical interaction: (ELISA (Raf-MEK-ERK cascade kinase assay, acti... -
NON-PROTEIN TARGET IC50 = 1.0 nM 9.0 Growth inhibition of human COLO205 cells incubated for 72 hrs by Cell-titer-Glo ... -
NON-PROTEIN TARGET IC50 = 1.0 nM 9.0 Growth inhibition of human COLO205 cells at 1:10 molar ratio of compound in pres... -
NON-PROTEIN TARGET IC50 = 1.0 nM 9.0 Growth inhibition of human HT-29 cells at 1:10 molar ratio of compound in presen... -
NON-PROTEIN TARGET IC50 = 1.0 nM 9.0 Growth inhibition of human MV522 cells at 1:10 molar ratio of compound in presen... -
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 1.6 nM 8.8 Inhibition of B-Raf activated MEK2 (unknown origin) assessed as ERK2-mediated MB... -
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 1.6 nM 8.8 Selectivity interaction (ELISA (Raf-MEK-ERK cascade kinase assay, activated with... -
Dual specificity mitogen-activated protein kinase kinase 1 IC50 = 1.8 nM 8.74 Affinity Biochemical interaction: (ELISA (Raf-MEK-ERK cascade kinase assay, acti... -
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 1.8 nM 8.74 Inhibition of MEK2 (unknown origin) 33539089
Dual specificity mitogen-activated protein kinase kinase 2 IC50 = 1.8 nM 8.74 Non competitive inhibition of MEK2 (unknown origin) 33539089
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 IC50 = 2.0 nM 8.7 Inhibition of MEK 1/2 (unknown origin) 33970631
NON-PROTEIN TARGET IC50 = 2.0 nM 8.7 Growth inhibition of human NCI-H727 cells incubated for 72 hrs by Cell-titer-Glo... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5303304 U2OS 10
- 10.6019/CHEMBL5444388 Dual specificity mitogen-activated protein kinase kinase 1 10
- 10.6019/CHEMBL5444388 Dual specificity mitogen-activated protein kinase kinase 2 10
26254279 10.18632/oncotarget.4214 Dual specificity mitogen-activated protein kinase kinase; MEK1/2 9
- 10.6019/CHEMBL5724696 U2OS 8
38457912 10.1016/j.bmc.2024.117674 NCI-H358 7
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
29191878 10.1126/science.aan4368 Unchecked 5
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
37130350 10.1021/acs.jmedchem.2c01844 A549 4
38457912 10.1016/j.bmc.2024.117674 ADMET 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
- 10.6019/CHEMBL5303304 HEK-293T 4
- 10.6019/CHEMBL5465560 Dual specificity mitogen-activated protein kinase kinase 1 3
29133594 10.1158/1541-7786.mcr-17-0468 Tyrosine-protein kinase receptor UFO 3
29133594 10.1158/1541-7786.mcr-17-0468 Dual specificity mitogen-activated protein kinase kinase 1 3
29133594 10.1158/1541-7786.mcr-17-0468 Dual specificity mitogen-activated protein kinase kinase 2 3
- 10.6019/CHEMBL5465560 Dual specificity mitogen-activated protein kinase kinase 2 2

Data from ChEMBL 36 via Core Engine