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Losmapimod (GSK-AHAB, GW856553X, SB856553) is a selective, potent, orally active p38 MAPK inhibitor with pKi of 8.1 and 7.6 for p38α and p38β, respectively; displays no significant activity for p38γ, p38δ (<25% inhibition at 10 uM), and COX-2; significantly and dose-dependently improves survival, endothelial-dependent and -independent vascular relaxation in rat model of cardiovascular disease.


Phase 3 Clinical


SB 202190


SB 202190 (SB202190, SB-202190) is a potent inhibitor p38α and p38β with IC50 of 50 nM and 100 nM respectively; stimulates the activity of CPP32-like caspases, potentiates apoptosis induced by Fas(APO-1) ligation or UV irradiation.




A potent and selective p38α kinase inhibitor with IC50 of 9 nM; shows 20-fold selectivity for p38α over p38β (Ki=220 nM) and no significant inhibition for MAP kinases (with the exception of MKK6); exhibits inhibition of PBMC IL-1β and TNFα IC50 of 45 and 51 nM, respectively; possesses favorable PK profile, and demonstrates good in vivo activity in models of inflammation.

Alzheimer's Disease

Phase 2 Clinical



CDD-450 is an unique inhibitor that selectively blocks p38α activation of proinflammatory kinase MAPK-MK2 while sparing p38α activation of PRAK and ATF2; shows no effect on NLRP3 expression, but decreases IL-1β expression by promoting IL-1β mRNA degradation; accelerates TNF-α and IL-6 mRNA decay, inhibites inflammation in mice with cryopyrinopathy, and is as efficacious as global p38α inhibitors in attenuating arthritis in rats and cytokine expression by cells from patients with cryopyrinopathy and rheumatoid arthritis.


948842-66-8 BMS-751324 is a novel clinical prodrug of BMS-582949, which is a highly selective p38α MAPK inhibitor with IC50 of 13 nM; BMS-751324 is effectively bioconverted into parent drug BMS-582949 in vivo by alkaline phosphatase and esterase in a stepwise manner; demonstrates similar efficacy in rat LPS-induced TNFα pharmacodynamic model and rat adjuvant arthritis model compared with BMS-582949; BMS-751324 is indeed effective in addressing the pH-dependent absorption issue associated with BMS-582949.


1229606-73-8 RV1088 is a potent narrow spectrum kinase inhibitor that target p38, c-Src, Syk or JAK individually, dose-dependently reduces TNF-α levels in LPS-activated macrophages with IC50 of 0.63 nM; also reduces IL-6 production effectively with IC50 of 1.66 nM, RV1088 is significantly more effective at inhibiting IL-6 and IL-8 production by monocytes and RA synovial fibroblasts compared with Humira; TNF-α, IL-6 and IL-8 synthesis in RA synovial membrane cells with low nM IC50s.


1220626-82-3 JNJ-49095397 (RV-568) is a specific narrow-spectrum kinase inhibitor that inhibits a selected set of kinases involved in COPD inflammation with IC50 of 5, 40 and 52 nM for p38α, p38γ and HCK, respectively; shows potent anti-inflammatory effects in monocytes and macrophages, demonstrates synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model combined with corticosteroid.


Phase 2 Clinical

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