ZY15557, a novel, long acting inhibitor of dipeptidyl peptidase-4, for the treatment of Type 2 diabetes mellitus.

ABSTRACT:

Background and purpose

Dipeptidyl peptidase (DPP)-4 inhibitors increase levels of glucagon-like peptide-1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. As longer acting inhibitors have therapeutic advantages, we developed a novel DPP-4 inhibitor, ZY15557, that has a sustained action and long half-life.

Experimental approach

We studied the potency, selectivity, efficacy and duration of action of ZY15557, in vitro, with assays of DPP-4 activity. In vivo, the pharmacodymamics and pharmacokinetics of ZY15557 were studied, using db/db mice and Zucker fatty rats, along with normal mice, rats, dogs and non-human primates.

Key results

ZY15557 is a potent, competitive and long acting inhibitor of DPP-4 (K_i 5.53 nM; K_off

SUBMITTER: Jain MR 

PROVIDER: S-EPMC5481660 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature