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Updated: Apr 27, 2026

An In Ovo Model for Testing Insulin-mimetic Compounds
Published on: April 23, 2018
Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin
Zeng-Wei Lai1, Chunhong Li1, Jun Liu2
1State Key Laboratory of Natural Medicines and Center of Drug Discovery, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, PR China.
Abstract:
Highly potent DPP-4 inhibitors have been identified by hybrid compound design based on linagliptin and alogliptin. The most promising compound 2h (IC50 = 0.31 nM) exhibited 8.5-fold and 2.5-fold more potent activity than that of alogliptin (IC50 = 2.63 nM) and linagliptin (IC50 = 0.77 nM), respectively. Compound 2h had a good inhibition selectivity for DPP-4 over DPP-8/9 and thus was selected for further biological evaluation, including oral glucose tolerance, plasma DPP-4 inhibitory activity, pharmacokinetic profile, acute toxicity and hERG inhibition. The assay results showed that 2h displayed significant in vivo glucose-lowering effect and low risk of toxicity. Further studies are expected to confirm 2h as a potential drug candidate for the treatment of type 2 diabetes.
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