MEK162 (ARRY-162, ARRY-438162)
ARRY-438162 is a potent inhibitor of MEK1/2 with IC50 of 12 nM.
CEP-32496 is a highly potent inhibitor of BRAF(V600E/WT) and c-Raf with Kd of 14 nM/36 nM and 39 nM, also potent to Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2, respectively; insignificant affinity for MEK-1, MEK-2, ERK-1 and ERK-2. Phase 1/2.
Features:High binding affinity for both BRAF (V600E) mutation and related c-Raf, but no significant affinity for other kinases of MAPK pathway.
Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.
SB203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM.
Features:First reported p38 inhibitor.
BIRB 796 (Doramapimod)
BIRB 796 (Doramapimod) is a highly selective p38α MAPK inhibitor with Kd of 0.1 nM, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2, ZAP-70, EGFR, HER2, PKA, PKC, PKCα/β/γ.
Features:The first p38 MAPK inhibitor to be tested in a phase III clinical trial.
SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo.
LY2228820 is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM, does not alter p38 MAPK activation. Phase 1/2.
VX-702 is a highly selective inhibitor of p38α MAPK, 14-fold higher potency against the p38α versus p38β. Phase 2.
Features:Highly selective, orally active inhibitor of p38 MAPK.
PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2.
VX-745 is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.
Features:A potent and selective inhibitor to p38α and p38β MAPK.