SB202190 (FHPI)

Selective p38 MAPK Inhibitor

BIRB 796 (Doramapimod) : p38α-selective, Kd=0.1 nM.

Most Potent p38 MAPK Inhibitor

Skepinone-L ^New : p38α-MAPK, IC50=5 nM.

p38 MAPK Inhibitor in Clinical Trial

VX-702 : Phase II for Rheumatoid Arthritis.

Newest p38 MAPK Inhibitor

Skepinone-L ^New : Selective p38α-MAPK inhibitor with IC50 of 5 nM.

Pexmetinib (ARRY-614) ^New

Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.

SB239063 ^New

SB239063 is a potent and selective p38 MAPKα/β inhibitor with IC50 of 44 nM, showing no activity against the γ- and δ-kinase isoforms.

GDC-0994 ^New

GDC-0994 is a potent, orally available and highly selective ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. Phase 1.

SB203580

SB203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 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.

Doramapimod (BIRB 796)

Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with K_d of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.

Features:The first p38 MAPK inhibitor to be tested in a phase III clinical trial.

Ralimetinib (LY2228820)

Ralimetinib (LY2228820) is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, does not alter p38 MAPK activation. Phase 1/2.

Losmapimod (GW856553X)

Losmapimod (GW856553X) is a selective, potent, and orally active p38 MAPK inhibitor with pK_i of 8.1 and 7.6 for p38α and p38β, respectively. Phase 3.

PH-797804

PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM in a cell-free assay; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2.

VX-702

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.

TAK-715

TAK-715 is a p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, 28-fold more selective for p38α over p38β, no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1. Phase 2.