KA2507 hydrochloride is a powerful and specific HDAC6 inhibitor, possessing an IC50 value of 2.5 nM. It displays no substantial toxicities while demonstrating significant antitumor efficacy and immune modulatory effects [1].

KA2507 hydrochloride does not prevent the proliferation of mouse or human cancer cells at selective concentrations for HDAC6 inhibition in vitro. Anti-proliferative effects manifest only at higher concentrations of KA2507 hydrochloride, accompanied by heightened acetylation of histone H3, indicating that these effects are due to off-target inhibition of class I HDAC and HDAC6 [1].

KA2507 hydrochloride, administered orally at doses between 100-200 mg/kg daily for 20 days, demonstrated significant inhibition of tumor growth in the syngeneic B16-F10 mouse melanoma model and showed antitumor efficacy in CT26 and MC38 colorectal cancer models. This compound not only reduced STAT3 activation (indicated by decreased phospho-STAT3 levels) - a crucial suppressor of antitumor immune responses - but also lowered PD-L1 expression and increased MHC class I expression, highlighting its potential in modulating antitumor immunity. However, KA2507 hydrochloride exhibited limited oral bioavailability (15% in mice) and a maximum concentration (Cmax) of 300 ng/mL at a dosage of 200 mg/kg. This pharmacokinetic profile was established through studies in male C57BL/6 mice utilizing the B16-F10 melanoma model.