Description
Doramapimod (285983-48-4) potently and selectively inhibits p38 MAPK by simultaneously binding to the ATP-binding domain and an allosteric site.1?(IC50=18 nM). Displays anti-inflammatory activity2?but differential effects on inflammatory genes3. Cell permeable.
Chemical Properties
Pale Beige Solid
Uses
Doramapimod is a highly potent inhibitor of p38 mitogen-activated protein kinase (MAPK). Doramapimod is a potential agent for the treatment of inflammatory diseases. Doramapimod blocks baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation leading to enhanced cytotoxicity and caspase activation.
Definition
ChEBI: A member of the class of pyrazoles that is an immunomodulator used for treatment of rheumatoid arthritis, Crohn's disease and psoriasis.
in vitro
birb 796 is a picomolar inhibitor of human p38 map kinase with a 12,000-fold increase in binding affinity. moreover, birb 796 behavors as one of the most potent and slowest dissociating human p38 map kinase inhibitors now known [1].
in vivo
in a lps-stimulated tnf-α synthesis mouse model, a 65% inhibition of tnf-α synthesis was observed when birb 796 was dosed orally at 10 mg/kg. in a model of established collagen-induced arthritis using b10.riii mice, birb 796 showed a 63% inhibition of arthritis severity when dosed orally at 30 mg/kg qd [2].
References
1) Pargellis?et al. (2002),?Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site; Nat. Struct. Biol.,?9?268
2) Branger?et al.?(2002),?Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia; J. Immunol.,?168?4070
3) Joos?et al. (2010),?Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1 beta-stimulated human chondrocytes; Br. J. Pharmacol.,?160?1252
