Endocrine/Metabolic
Cell culture studies suggest inhibiting TGFBR1 could help treat GLIS3-mutant diabetes. Screening of a library of approved drugs, drug-like compounds and tool compounds in GLIS3-knockout human pancreatic progenitor β cells identified that the TGFBR1 inhibitor galunisertib inhibited apoptosis with an IC50 of 1.4 μM. Also in the cells, galunisertib increased the number of insulin-positive cells compared with vehicle, and four tool compound TGFBR1 inhibitors decreased markers of apoptosis and necrosis. Next steps could include testing TGFBR1 inhibitors in animal models of GLIS3-mutant diabetes.
Eli Lilly and Co. has galunisertib (LY2157299) in Phase II testing for glioblastoma and hepatocellular carcinoma (HCC) and Phase I/II testing for pancreatic cancer...