Adezmapimod (SB 203580) hydrochloride is a selective ATP-competitive inhibitor of p38 MAPK, displaying IC50 values of 50 nM for SAPK2a/p38 and 500 nM for SAPK2b/p38β2. This compound also inhibits LCK, GSK3β, and PKBα, albeit with IC50 values 100-500 times higher than those for SAPK2a/p38. Additionally, Adezmapimod hydrochloride acts as an activator of autophagy and mitophagy [1].

Adezmapimod hydrochloride, when preincubated at concentrations of 0-30 μM for 1 hour and subsequently cultured with 20 ng/mL of IL-2 for 24 hours, effectively inhibits the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, and BAF F7 B cells, exhibiting an inhibitory concentration (IC50) range of 3-5 μM. Additionally, Adezmapimod hydrochloride impedes PKB phosphorylation and the phosphorylation of Ser473 in a dose-dependent manner across these cell lines. Through cell proliferation assays and western blot analysis, it has been demonstrated that Adezmapimod hydrochloride halts the proliferation and specific phosphorylation events within CT6, BA/F3 cell line F7, and PBMC/T cells when treated under specified conditions, indicating its significant effect on these biological processes in a controlled environment.

Administering Adezmapimod hydrochloride (5 mg/kg/day; intra peritoneally for 16 consecutive days) to six-week-old female atymic Nu/Nu mice harboring CAL27 p38WT and p38TM tumors resulted in a markedly reduced tumor size in the p38WT tumors, whereas the p38TM tumors remained unaffected by the treatment. This observation was made after a treatment period spanning two weeks, indicating a differential response based on tumor type [1].