Givinostat hydrochloride (ITF2357 hydrochloride) is an inhibitor of HDAC with IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride exhibits anti-inflammatory, anti-angiogenic, and antineoplastic activities.

HDAC10 (human):340 nM (IC50), HD1-B:7.5 nM (IC50), HD2:10 nM (IC50), HDAC6 (human):315 nM (IC50), HDAC3 (human):157 nM (IC50), HDAC8 (human):854 nM (IC50), HDAC2 (human):325 nM (IC50), HDAC7 (human):524 nM (IC50), HDAC1 (human):198 nM (IC50), HDAC11 (human):292 nM (IC50), HDAC4 (human):1059 nM (IC50), HD1-A:16 nM (IC50), HDAC9 (human):541 nM (IC50), HDAC5 (human):532 nM (IC50)

Givinostat hydrochloride inhibits JS-1 cell proliferation in a concentration-dependent manner. Givinostat hydrochloride (≥500 nM) is associated with significant inhibition of JS-1 cell proliferation. Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat hydrochloride ≥250 nM plus LPS and the group without LPS treatment[3]. Givinostat hydrochloride (25, 50, and 100 nM) reduces IL-1β secretion more than 70%. Givinostat hydrochloride suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM, but at 100 and 200 nM, there is no reduction[4].

Givinostat hydrochloride (10 mg/kg) reduces serum TNFα by 60%. Pretreatment of Givinostat hydrochloride (0.1 mg/kg) significantly reduces the circulating TNFα by nearly 90%[4].