GSK620 is an orally active, pan-Bromodomain and Extra-Terminal protein Bromodomain 2 (pan-BET BD2) selective inhibitor. GSK620 is highly selective for the BET-BD2 family of proteins, with more than 200-fold selectivity over all other bromodomains[1].
In vitro, the IC₅₀ values of GSK620 in GSC23 and GSC11 cells were 38.74μM and 35.39μM, respectively. Treatment with GSK620 at 0.5-5μM for 24-48h effectively downregulated Mesenchymal (MES) gene expression in glioblastoma (GBM) models. In GSC11 and GSC23 cells, 1μM GSK620 for 24h reduced chromatin-bound BD2 and its occupancy at MES promoters; 0.5μM inhibited invasion, and 0.5-5μM suppressed colony formation[2].
In vivo, GSK620, administered orally in mice, has a plasma half-life of 1.05h and exhibits brain penetration. Oral GSK620 (30mg/kg; once daily for 8 days) significantly prolonged survival versus vehicle controls and reduced tumor-associated macrophage (TAM) infiltration by IHC in an orthotopic xenograft model[2].
References:
[1] Jonathan T Seal, et al. J Med Chem. 2020 Sep 10;63(17):9093-9126. [2] Massimo Petretich, et al. Curr Opin Chem Biol . 2020 Aug;57:184-193.
[2] Vadla R, Taylor B, Miyake Y, et al. BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma. Neuro Oncol. 2025;27(11):2828-2842.
GSK620是一种具有口服活性的泛溴结构域和末端外结构域蛋白第二溴结构域的（pan-BET BD2）选择性抑制剂。GSK620对BET蛋白的BD2结构域具有高度选择性，其对BD2的选择性相较于所有其他溴结构域高出200倍以上[1]。
体外实验中，GSK620在GSC23和GSC11细胞中的IC₅₀值分别为38.74μM和35.39μM。GSK620（0.5-5μM；24-48h）可下调胶质母细胞瘤（GBM）模型中间质型（MES）基因的表达。GSC11和GSC23细胞中，1μM GSK620处理24小时可降低染色质结合的BD2及其在MES启动子上的占位。0.5μM GSK620处理24小时抑制细胞侵袭，0.5-5μM GSK620处理24小时抑制克隆形成。
体内实验中，GSK620在小鼠中经口服给药后，血浆半衰期为1.05小时，并具有脑部渗透性。口服给予GSK620（30mg/kg；每日一次；持续8天）在原位异种移植模型中显著延长了小鼠的生存期，并通过免疫组化显示肿瘤相关巨噬细胞（TAM）浸润减少。