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.