BRD3308

BRD3308 is a highly selective HDAC3 inhibitor with an IC₅₀ of 54 nM. BRD3308 is 23-fold selectivity for HDAC3 over HDAC1 (IC₅₀ of 1.26 μM) or HDAC2 (IC₅₀ of 1.34 μM). BRD3308 suppresses pancreatic β-cell apoptosis induced by inflammatory cytokines or glucolipotoxic stress, and increases functional insulin release. BRD3308 activates HIV-1 transcription and disrupts HIV-1 latency^[1][2][3]. In Vitro: BRD3308 (5-30 µM; 6-24 hours) treatment increases HIV-1 expression in the 2D10 cell line^[1].
BRD3308 (15 µM; overnight) is able to induce outgrowth of HIV-1 from latently infected cells ex vivo in resting CD4+ T cells^[1]. BRD3308 inhibits HDAC1, HDAC2 and HDAC3 with K_i values of 5.1 μM, 6.3 μM and 29 nM, respectively^[3]. In Vivo: BRD3308 (5 mg/kg; intraperitoneal injection; every second day; male Zucker Diabetic Fatty rats) treatment reduces hyperglycaemia and increases insulin secretion in a rat model of type 2 diabetes. At the end of the hyperglycaemic clamp, circulating insulin levels are significantly higher in BRD3308-treated rats. Pancreatic insulin staining and contents are also significantly higher. BRD3308 preserves the functional β-cell mass against glucolipotoxicity in vivo^[2].