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 inhibit the in vitro proliferation of mouse or human cancer cells at concentrations that are selective for HDAC6 inhibition. The anti-proliferative effects are only observed at high concentrations of KA2507 hydrochloride, which combines with the increased acetylation of histone H3 suggests that the anti-proliferative effects of KA2507 hydrochloride are attributable to off-target inhibition of class I HDAC as well as HDAC6 [1].

KA2507 hydrochloride (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model [1]. KA2507 hydrochloride also demonstrates antitumor efficacy in CT26 and MC38 colorectal cancer models [1]. Analysis of tumor samples also indicates modulation of biomarkers of antitumor immunity at efficacious dosing, with KA2507 hydrochloride administration resulting in reduced STAT3 activation (as measured by phospho-STAT3, an important suppressor of the antitumor immune response), reduced PD-L1 expression, and increased expression of MHC class I [1]. KA2507 hydrochloride exhibits poor oral bioavailability (mice 15%) and C max (mice 300 ng/mL) following oral administration (mice 200 mg/kg) [1]. Animal Model: Male C57BL/6 mice, B16-F10 melanoma model [1] Dosage: 100 mg/kg, 200 mg/kg, Administration: P.o.; once a day for 20 days Result: Inhibited tumor growth in the syngeneic B16-F10 mouse melanoma model. Animal Model: Male C57BL/6 mice, B16-F10 melanoma model [1] Dosage: 200 mg/kg (Pharmacokinetic Analysis) Administration: Oral administration Result: Oral bioavailability (15%), C max (300 ng/mL).