TRAMETINIB

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Synonyms
Status
Molecule Category UNKNOWN
ATC L01EE01
UNII 33E86K87QN

Structure

InChI Key LIRYPHYGHXZJBZ-UHFFFAOYSA-N
Smiles CC(=O)Nc1cccc(-n2c(=O)n(C3CC3)c(=O)c3c(Nc4ccc(I)cc4F)n(C)c(=O)c(C)c32)c1
InChI
InChI=1S/C26H23FIN5O4/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34)

Physicochemical Descriptors

Property Name Value
Molecular Formula C26H23FIN5O4
Molecular Weight 615.4
AlogP 3.94
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 5.0
Polar Surface Area 107.13
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 37.0

Bioactivity

Mechanism of Action Action Reference
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor INHIBITOR FDA Other FDA
Protein: Dual specificity mitogen-activated protein kinase kinase; MEK1/2
Description: Dual specificity mitogen-activated protein kinase kinase 2
Organism : Homo sapiens
P36507 ENSG00000126934
Protein: Dual specificity mitogen-activated protein kinase kinase; MEK1/2
Description: Dual specificity mitogen-activated protein kinase kinase 1
Organism : Homo sapiens
Q02750 ENSG00000169032
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE7 family
- 1-3 - - -
Transporter Primary active transporter ATP-binding cassette ABCB subfamily
247 - - - -
Assay Description Organism Bioactivity Reference
Inhibition of B-Raf activated MEK2 (unknown origin) assessed as ERK2-mediated MBP phosphorylation after 30 mins by ELISA Homo sapiens 1.6 nM
Inhibition of B-Raf activated MEK1 (unknown origin) assessed as ERK2-mediated MBP phosphorylation after 30 mins by ELISA Homo sapiens 3.4 nM
Growth inhibition of human MDA-MB-175-VII cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 96.0 nM
Growth inhibition of human RKO cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 18.0 nM
Growth inhibition of human HCT8 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 55.0 nM
Growth inhibition of human NCI-H508 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 23.0 nM
Growth inhibition of human DLD1 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 632.0 nM
Growth inhibition of human T84 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 61.0 nM
Growth inhibition of human KM12 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 23.0 nM
Growth inhibition of human SW837 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 74.0 nM
Growth inhibition of human LS1034 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 5.0 nM
Growth inhibition of human COLO205 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 1.0 nM
Growth inhibition of human SW1463 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 4.0 nM
Growth inhibition of human HT-29 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 2.0 nM
Growth inhibition of human SW480 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 37.0 nM
Growth inhibition of human SW1417 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 3.0 nM
Growth inhibition of human COR-L23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 329.0 nM
Growth inhibition of human A549 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 34.0 nM
Growth inhibition of human NCI-H1355 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 52.0 nM
Growth inhibition of human NCI-H1792 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 53.0 nM
Growth inhibition of human NCI-H23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 29.0 nM
Growth inhibition of human Calu6 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 4.0 nM
Growth inhibition of human MV522 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 2.0 nM
Growth inhibition of human SW900 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 127.0 nM
Growth inhibition of human A427 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 22.0 nM
Growth inhibition of human Calu3 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 158.0 nM
Growth inhibition of human NCI-H727 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 2.0 nM
Growth inhibition of human MDA-MB-175-VII cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 16.0 nM
Growth inhibition of human EFM19 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 30.0 nM
Growth inhibition of human RKO cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 5.0 nM
Growth inhibition of human HCT8 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 14.0 nM
Growth inhibition of human NCI-H508 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 8.0 nM
Growth inhibition of human DLD1 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 93.0 nM
Growth inhibition of human T84 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 30.0 nM
Growth inhibition of human KM12 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 10.0 nM
Growth inhibition of human SW837 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 25.0 nM
Growth inhibition of human LS1034 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 4.0 nM
Growth inhibition of human COLO205 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 1.0 nM
Growth inhibition of human SW1463 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 4.0 nM
Growth inhibition of human HT-29 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 1.0 nM
Growth inhibition of human SW480 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 26.0 nM
Growth inhibition of human SW1417 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 3.0 nM
Growth inhibition of human COR-L23 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 37.0 nM
Growth inhibition of human A549 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 16.0 nM
Growth inhibition of human NCI-H1355 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 27.0 nM
Growth inhibition of human NCI-H1792 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 35.0 nM
Growth inhibition of human NCI-H23 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 20.0 nM
Growth inhibition of human Calu6 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 3.0 nM
Growth inhibition of human MV522 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 1.0 nM
Growth inhibition of human NCI-H1155 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 10.0 nM
Growth inhibition of human SW1573 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 38.0 nM
Growth inhibition of human HOP62 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 50.0 nM
Growth inhibition of human SW900 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 72.0 nM
Growth inhibition of human A427 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 10.0 nM
Growth inhibition of human HCC827 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 40.0 nM
Growth inhibition of human Calu3 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 39.0 nM
Growth inhibition of human NCI-H727 cells at 1:10 molar ratio of compound in presence of N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecar- boxamide incubated for 72 hrs by Cell-titer-Glo reagent based assay Homo sapiens 2.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 62.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 9.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 76.63 %
Antiproliferative activity against human A375 cells assessed as reduction in cell viability Homo sapiens 0.74 nM
Inhibition of ERK1/2 phosphorylation at Thr202/Tyr204 residues in human MIAPaCa2 cells grown under 3D anchorage-independent soft-agar conditions at 50 nM incubated for 2 to 8 hrs by Western blotting analysis relative to control Homo sapiens 65.0 %
Inhibition of ABCB1 in human A2780/ADR cells assessed as potentiation of daunorubicin-induced cytotoxicity measured after 72 hrs by MTT assay Homo sapiens 247.0 nM
Inhibition of MEK1 (unknown origin) Homo sapiens 0.7 nM
Inhibition of MEK2 (unknown origin) Homo sapiens 14.9 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 19.64 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 8.399 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.19 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.36 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.36 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.19 %
Antiproliferative activity against human A375 cells harboring BRAF V600E mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Homo sapiens 2.4 nM
Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Homo sapiens 18.0 nM
Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Homo sapiens 19.0 nM
Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Homo sapiens 460.0 nM
Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Homo sapiens 3.0 nM
Antiproliferative activity against human KYSE-520 cells Homo sapiens 10.0 nM
Inhibition of MEK in human KYSE-520 cells assessed as reduction in p-ERK levels Homo sapiens 1.0 nM

Cross References

Resources Reference
ChEBI 75998
ChEMBL CHEMBL2103875
DrugBank DB08911
DrugCentral 4802
FDA SRS 33E86K87QN
Guide to Pharmacology 6495
PDB QOM
PharmGKB PA166115364
PubChem 11707110
SureChEMBL SCHEMBL170938
ZINC ZINC000043100709
CONTENTS