WS6 is a small molecule that promotes β cell proliferation in rodent and human primary islets with EC50 of 0.28 μM (R7T1 cell viability). WS6 also stimulates α cell proliferation in human pancreatic islets. WS6 appears to act by inhibiting IKKε and blocking the ability of EBP1 to suppress E2F-medtiated transcription.
WS6 is a novel small molecule that promotes β cell proliferation in rodent and human primary islets with EC50 of 0.28 uM(R7T1 cell viability). EC50 value: 0.28 uM. RIP-DTA mice were fed Dox in the drinking water until the onset of overt diabetes (blood glucose reading >300 mg/dL, typically 4-10 days), at which point Dox treatment was discontinued and treatment with WS6 was initiated (5 mg/kg every other day via intraperitoneal injection). Pharmacokinetic studies with WS6 at 50 mg/kg revealed a CMAX of ～5 μM and T1/2 of ～2 h. Treatment with WS6 caused a progressive reduction of blood glucose over time, starting around 2 weeks[3]. Enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. WS6, an IkB kinase and EBP1 inhibitor, can promote effective human β-cell proliferation[4]. WS6 did not change the proportion of insulin-positive beta cells or the expression of beta cell-specific transcription factors, suggesting that WS6 does not alter beta cell differentiation, and WS6 had no effect on human islet cell apoptosis or viability[5].
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