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
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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)
1. Alten RE, Zerbini C, Jeka S, Irazoque F, Khatib F, Emery P, Bertasso A, Rabbia M, Caulfield JP. (2010)
Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy.
Ann Rheum Dis, 69 (2): 364-7. [PMID:19357113]
2. Cohen S, Fleischmann R. (2010)
Kinase inhibitors: a new approach to rheumatoid arthritis treatment.
Curr Opin Rheumatol, 22 (3): 330-5. [PMID:20164774]
3. Cohen SB, Cheng TT, Chindalore V, Damjanov N, Burgos-Vargas R, Delora P, Zimany K, Travers H, Caulfield JP. (2009)
Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis.
Arthritis Rheum, 60 (2): 335-44. [PMID:19180516]
4. Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J et al.. (2011)
Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase.
J Med Chem, 54 (7): 2255-65. [PMID:21375264]
5. Joos H, Albrecht W, Laufer S, Brenner RE. (2010)
Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1beta-stimulated human chondrocytes.
Br J Pharmacol, 160 (5): 1252-62. [PMID:20590617]
6. Zhang X, Huang Y, Navarro MT, Hisoire G, Caulfield JP. (2010)
A proof-of-concept and drug-drug interaction study of pamapimod, a novel p38 MAP kinase inhibitor, with methotrexate in patients with rheumatoid arthritis.
J Clin Pharmacol, 50 (9): 1031-8. [PMID:20100913]