Pamapimod (R-1503, Ro4402257) is a novel, selective inhibitor of p38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p3
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
MAP kinase p38 alpha inhibitor
Product Description
Information
Pamapimod (R-1503, Ro4402257) is a novel, selective inhibitor ofp38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p38gamma isoforms.
Pamapimod inhibited p38, but inhibition of JNK was not detected. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production by monocytes, interleukin (IL)-1β production in human whole blood, and spontaneous TNFα production by synovial explants from RA patients.
In vivo
In murine collagen-induced arthritis, pamapimod reduced clinical signs of inflammation and bone loss at 50 mg/kg or greater. In a rat model of hyperalgesia, pamapimod increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation. Pamapimod suppresses spontaneous production of TNFα by synovial explants from RA patients. LPS- and TNFα-stimulated production of TNFα and IL-6 in rodents also was inhibited by pamapimod.
1.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]
2.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]
3.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]
4.Cohen S, Fleischmann R. (2010) Kinase inhibitors: a new approach to rheumatoid arthritis treatment.. Curr Opin Rheumatol, 22 (3):(330-5). [PMID:20164774]
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.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]
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