ide 1

IDE1 can induce definitive endoderm from embryonic stem cells. It has been shown to induce the differentiation of Sox17+/FoxA2+-expressing pancreatic progenitors from human and mouse embryonic stems cells (EC50: 125.5 nM in vitro) by activating the TGF-β signaling pathway. IDE1-derived endodermal cells injected into E8.75 mouse embryos ex vivo have been shown to incorporate into the developing gut tube, contributing to its formation.

Hit 1 is an activator of insulin-degrading enzymes (IDE) (EC50: 5.5 μM) and reduces glucose-stimulated insulin secretion.

Insulin-degrading enzyme (IDE) is a thiol-sensitive zinc-metallopeptidase that acts as the major insulin-degrading protease in vivo, mediating the termination of insulin signaling. [1] In addition to regulating insulin action in diabetes pathogenesis, IDE plays a role in Varicella-Zoster virus infection and degradation of amyloid-β, a peptide implicated in Alzheimer's disease. ML-345 is a small molecule inhibitor that selectively targets cysteine819 in IDE with an EC50 value of 188 nM. [2] It demonstrates 10-fold selectivity for IDE over a panel of enzymes with reactive cysteine residues.[2] Reference：[1]. Maianti, J.P., McFedries, A., Foda, Z.H., et al. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature 511(7507), 94-98 (2014).[2]. Bannister, T.D., Wang, H., Abdul-Hay, S.O., et al. ML345, a small-molecule inhibitor of the insulin-degrading enzyme (IDE). 1 R03 DA024888-01 (MLSCN cycle 6), 1-41 (2014).