pexmetinib   Click here for help

GtoPdb Ligand ID: 9917

Synonyms: ARRY-614 | ARRY614
Compound class: Synthetic organic
Comment: Pexmetinib is an orally bioavailable small-molecule inhibitor of p38 MAPK (β isoforms) and Tie2 kinases [2]. It is a type 2 kinase inhibitor that binds both Tie2 and p38 MAP kinases in the "DFG-out" conformation. p38 MAPK is a proinflammatory kinase, Tie2 is an endothelial cell specific receptor tyrosine kinase and is the receptor for angiopoietin-1. Concomitant inhibition of these kinases is predicted to produce antineoplastic, anti-inflammatory and antiangiogenic effects that would provide a novel anti-cancer therapeutic, in particular for the treatment of myelodysplastic syndromes (MDS) [1,4] and acute myeloid leukemia (AML).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 105.71
Molecular weight 556.26
XLogP 5.49
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OCCn1ncc2c1ccc(c2)Oc1ccc(cc1CNC(=O)Nc1cc(nn1c1ccc(cc1)C)C(C)(C)C)F
Isomeric SMILES OCCn1ncc2c1ccc(c2)Oc1ccc(cc1CNC(=O)Nc1cc(nn1c1ccc(cc1)C)C(C)(C)C)F
InChI InChI=1S/C31H33FN6O3/c1-20-5-8-24(9-6-20)38-29(17-28(36-38)31(2,3)4)35-30(40)33-18-22-15-23(32)7-12-27(22)41-25-10-11-26-21(16-25)19-34-37(26)13-14-39/h5-12,15-17,19,39H,13-14,18H2,1-4H3,(H2,33,35,40)
InChI Key LNMRSSIMGCDUTP-UHFFFAOYSA-N
Bioactivity Comments
In vitro, pexmetinib inhibits leukemic proliferation, and stimulates hematopoiesis in primary MDS specimens [2].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
ABL proto-oncogene 1, non-receptor tyrosine kinase Hs Inhibitor Inhibition 8.4 pIC50 - 2
⤷ pIC50 8.4 (IC50 4x10-9 M) [2]
ABL proto-oncogene 2, non-receptor tyrosine kinase Hs Inhibitor Inhibition 8.0 pIC50 - 2
⤷ pIC50 8.0 (IC50 1x10-8 M) [2]
LYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 7.6 pIC50 - 2
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [2]
mitogen-activated protein kinase 11 Hs Inhibitor Inhibition 7.6 pIC50 - 2
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [2]
HCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 7.6 pIC50 - 2
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [2]
misshapen like kinase 1 Hs Inhibitor Inhibition 7.6 pIC50 - 2
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [2]
mitogen-activated protein kinase 14 Hs Inhibitor Inhibition 7.5 pIC50 - 2
⤷ pIC50 7.5 (IC50 3.5x10-8 M) [2]
FYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 7.4 pIC50 - 2
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [2]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
TEK receptor tyrosine kinase Hs Inhibitor Inhibition 9.0 pIC50 - 2
⤷ pIC50 9.0 (IC50 1x10-9 M) [2]
fibroblast growth factor receptor 1 Hs Inhibitor Inhibition 7.6 pIC50 - 2
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [2]
fms related receptor tyrosine kinase 4 Hs Inhibitor Inhibition 7.4 pIC50 - 2
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [2]
fms related receptor tyrosine kinase 1 Hs Inhibitor Inhibition 7.3 pIC50 - 2
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [2]