GSK620

GSK620 is a potent, selective, orally active inhibitor of the second bromodomain (BD2) across the BET (Bromo and Extra-Terminal) protein family, chiefly targeting BRD2, BRD3, BRD4, and BRDT. It is a small molecule epigenetic modulator developed by GlaxoSmithKline as a tool compound to selectively inhibit BD2 over BD1 bromodomains (with selectivity greater than 200-fold over BD1). GSK620 exhibits excellent oral bioavailability, favorable pharmacokinetics, and broad-spectrum selectivity. In preclinical in vivo models of immunoinflammatory disease (e.g., inflammatory arthritis, psoriasis, nonalcoholic fatty liver disease), GSK620 showed robust anti-inflammatory and efficacy phenotypes, outperforming clinical benchmark therapies and pan-BET inhibitors in some settings. Mechanistically, its anti-inflammatory effects are mediated through selective interruption of BD2-dependent transcriptional regulation of pro-inflammatory genes, and it has been shown to reduce MCP-1 (CCL2) and key cytokines in human whole blood and animal models. The compound does not exhibit significant toxicity in preclinical safety screens and does not significantly inhibit major off-target proteins or induce reactive metabolite toxicity. GSK620 is a chemical probe tool rather than a clinically developed drug and is not approved for human use[1][2][4][5][11][13][14].