KA2507 hydrochloride 是一种高效、高选择性的 HDAC6 抑制剂 IC50=2.5 nM)，无明显毒性。KA2507 hydrochloride 具有抗肿瘤和免疫调节作用。
货号:ajcx33596
CAS:N/A
分子式:C16H15ClN6O2
分子量：358.78
溶解度:N/A
纯度：98%
存储：Store at -20°C
库存：现货

Background:

KA2507 hydrochloride is a potent and highly selective inhibitor of HDAC6 (IC50=2.5 nM) with no significant toxicities. KA2507 hydrochloride shows 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 Cmax (mice 300 ng/mL) following oral administration (mice 200 mg/kg)[1].

[1]. Tsimberidou AM, 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;27(13):3584-3594.