pamapimod   Click here for help

GtoPdb Ligand ID: 9915

Synonyms: compound 2b [PMID: 21375264] | Ro 4402257 | Ro-4402257 | Ro4402257
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Pamapimod is an ATP-competitive (Type I), orally bioavailable and highly selective inhibitor of p38α mitogen-activated protein kinase (MAPK14), that was developed for immunomodulatory potential [4].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 109.5
Molecular weight 406.15
XLogP 3.16
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES OCCC(Nc1ncc2c(n1)n(C)c(=O)c(c2)Oc1ccc(cc1F)F)CCO
Isomeric SMILES OCCC(Nc1ncc2c(n1)n(C)c(=O)c(c2)Oc1ccc(cc1F)F)CCO
InChI InChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)
InChI Key JYYLVUFNAHSSFE-UHFFFAOYSA-N
Bioactivity Comments
Pamapimod exhibits submicromolar binding affinity for only seven out of >300 kinases tested [4]. It binds p38α (MAPK14) and p38β (MAPK11), but not p38γ (MAPK12) or p38δ (MAPK13). Pamapimod potently inhibited cytokine production in a selection of in vitro and in vivo models, including inhibition of TNFα production by human monocytic THP-1 cells, and inhibition of LPS-induced IL-1β production in human whole blood.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase 14 Primary target of this compound Hs Inhibitor Inhibition 8.9 pKd - 4
pKd 8.9 (Kd 1.3x10-9 M) [4]
Description: In a biochemical assay.
mitogen-activated protein kinase 9 Hs Inhibitor Inhibition 7.8 pKd - 4
pKd 7.8 (Kd 1.6x10-8 M) [4]
Description: In a biochemical assay.
mitogen-activated protein kinase 10 Hs Inhibitor Inhibition 7.7 pKd - 4
pKd 7.7 (Kd 1.9x10-8 M) [4]
Description: In a biochemical assay.
mitogen-activated protein kinase 11 Hs Inhibitor Inhibition 6.9 pKd - 4
pKd 6.9 (Kd 1.2x10-7 M) [4]
Description: In a biochemical assay.
mitogen-activated protein kinase 8 Hs Inhibitor Inhibition 6.7 pKd - 4
pKd 6.7 (Kd 1.9x10-7 M) [4]
Description: In a biochemical assay.