KA2507 is a potent and selective HDAC6 inhibitor, with an IC50 of 2.5 nM. KA2507 shows antitumor activities and immune modulatory effects in preclinical models[1].
KA2507 did not inhibit the in vitro proliferation of mouse or human cancer cells at concentrations that are selective for HDAC6 inhibition[1].
KA2507 (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model[1].KA2507 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 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 exhibits poor oral bioavailability (mice 15%) and Cmax (mice 300 ng/mL) following oral administration (mice 200 mg/kg)[1].
[1]. Apostolia M Tsimberidou, et al. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021 May 4.