BRD-7389 #99734

The inhibitor BRD-7389 was originally isolated by screening a set of small molecules for detection of insulin protein production in a murine pancreatic α-cell line. BRD-7389 treatment of cells resulted in a dose-dependent increase in Ins2 mRNA and a number of β-cell markers. Similar results were seen in primary human islet cells. Further studies determined that BRD-7389 inhibited a number of protein kinases, and was most active against 90 kDa ribosomal S6 kinase (RSK) family members, with IC₅₀ values of 1.5 mM, 2.4 mM, and 1.2 mM for RSK1, RSK2, and RSK3, respectively (1). BRD-7389 inhibited RSK activity and blocked cell proliferation in colon cancer cells stimulated by muscarinic acetylcholine receptor activation (2). BRD-7389 and the unrelated RSK inhibitor BI-D1870 inhibited protein synthesis and cell proliferation in multiple dual-resistant melanoma patient-derived cells, suggesting a possible strategy in the treatment of drug-resistant melanoma (3).