J22352是一种具有类似靶向嵌合体蛋白水解(PROTAC)特性、高度选择性HDAC6抑制剂，其IC50值为4.7nM，J22352通过抑制胶质母细胞瘤自噬、诱发抗肿瘤免疫反应来促进HDAC6降解和诱导抗癌效果，并通过降低PD-L1的免疫抑制活性，使宿主抗肿瘤活性恢复。
J22352 is a PROTAC (proteolysis-targeting chimeras)-like and highly selective HDAC6 inhibitor with an IC50 value of 4.7 nM. J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma cancers, and leading to the restoration of host antitumor activity by reducing the immunosuppressive activity of PD-L1[1]. HDAC6|4.7 nM (IC50)
J22352 (0.1-20 μM; 72 hours) decreases U87MG cell viability in a dose-dependent manner[1]. J22352 (10 μM; 24 hours) shows a dose-dependent decrease in HDAC6 protein abundance[1]. Cell Viability Assay[1] Cell Line: U87MG cells
J22352 (10mg/kg; given i.p. per day for 14 days in male nude mice) results in a >80% tumor growth inhibition (TGI) rate. J22352 is well tolerated in mice[1]. Animal Model: Male nude mice (BALB/cAnN.Cg-Foxnlnu/CrlNarl, 4-6 weeks old)[1]
[1]. Liu JR, et al. High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma. Biochem Pharmacol. 2019 May; 163:458-471.
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