selonsertib   Click here for help

GtoPdb Ligand ID: 9040

Synonyms: GS-4997
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Selonsertib is an orally bioavailable apoptosis signal-regulating kinase 1 (ASK1= mitogen-activated protein kinase kinase kinase 5, MAP3K5) inhibitor being investigated for its anti-fibrotic activity. It is compound I in patent US8742126 [2]. Development as a treatment for nonalcoholic steatohepatitis (NASH) was unsuccessful.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 90
Molecular weight 445.2
XLogP 5.68
No. Lipinski's rules broken 1
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Canonical SMILES O=C(c1cc(c(cc1F)C)n1cnc(c1)C1CC1)Nc1cccc(n1)c1nncn1C(C)C
Isomeric SMILES O=C(c1cc(c(cc1F)C)n1cnc(c1)C1CC1)Nc1cccc(n1)c1nncn1C(C)C
InChI InChI=1S/C24H24FN7O/c1-14(2)32-13-27-30-23(32)19-5-4-6-22(28-19)29-24(33)17-10-21(15(3)9-18(17)25)31-11-20(26-12-31)16-7-8-16/h4-6,9-14,16H,7-8H2,1-3H3,(H,28,29,33)
Bioactivity Comments
Selonsertib is an ATP-competitive inhibitor. It prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation [2]. Selonsertib is a substrate of P-glycoprotein, with a high efflux ratio in a MDR1-MDCK assay, which makes it unsuitable for CNS applications [1].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase kinase kinase 5 Primary target of this compound Hs Inhibitor Inhibition 8.5 pIC50 - 2
pIC50 8.5 (IC50 3.2x10-9 M) [2]
Description: Determined is aTR-FRET immunoassay, measuring phosphorylation of a biotinylated peptide substrate by ASK1 kinase.