Adezmapimod

Adezmapimod (SB 203580) is a selective and ATP-competitive p38 MAPK inhibitor with IC₅₀s of 50 nM and 500 nM for SAPK2a/p38 and SAPK2b/p38β2, respectively. Adezmapimod inhibits LCK, GSK3β and PKBα with IC₅₀s of 100-500-fold higher than that for SAPK2a/p38. Adezmapimod can inhibit p38 MAPK and lead to the inhibition of downstream HSP27 phosphorylation. Adezmapimod does not disrupt JNK activity and is an autophagy and mitophagy activator^[1][2][3]. In Vitro:Adezmapimod (SB 203580) (preincubated with 0-30 μM for 1 h and cultured for 24 h in the presence of 20 ng/mL IL-2) prevents the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells with an IC₅₀ of 3-5 μM^[1].
SB203580 blocks PKB phosphorylation (IC₅₀ 3-5 μM). SB203580 inhibitsthe phosphorylation of Ser473 in a dose-dependent manner in both CT6 and activated human T cells and IL-2-responsive BA/F3 F7 B cells^[1]. In Vivo:Adezmapimod (SB 203580) (5 mg/kg/day; intra peritoneal injected daily for 16 consecutive days, in female atymic Nu/Nu mice) treatment, p38WT tumors show a significantly smaller tumor burden when compared with p38TM tumors that were treated in parallel^[1].