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Endocrine/metabolic disease


Solute carrier family 10 sodium-dependent bile acid transporter member 2 (SLC10A2; ASBT; IBAT)

In vitro and rodent studies identified benzothiazepine ASBT inhibitors that could help treat diabetes. In vitro, the lead analogs selectively inhibited ASBT with nanomolar IC50 values. In a rat model for type 2 diabetes, the lead compounds increased plasma insulin and decreased plasma glucose compared with vehicle. GlaxoSmithKline plc has completed Phase I testing of the lead compound (GSK2330672) to treat type 2 diabetes.
Albireo AB, Ajinomoto Co. Inc. and Ferring Pharmaceuticals A/S have the ASBT inhibitor elobixibat (A3309) in Phase III testing to treat constipation and
Phase II testing to treat irritable bowel syndrome (IBS).
Albireo's A4250, an ASBT inhibitor, is in preclinical development for diabetes, cirrhosis and other liver diseases.

SciBX 6(24); doi:10.1038/scibx.2013.602
Published online June 20, 2013

Patented; unavailable for licensing

Wu, Y. et al. J. Med. Chem.; published online May 16, 2013;
Contact: Jon L. Collins, GlaxoSmithKline Research & Development,
Research Triangle Park, N.C.