E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human and mouse DPP-IV with IC50 values of approximately 100 nM.

Enteroinsular axis of db/db mice and efficacy of dipeptidyl peptidase IV inhibition.

In type 2 diabetic patients, the administration of glucagon-like peptide-1 (GLP-1), known as an incretin, exerts antidiabetic effects. However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. DPPIV inhibition is thought to be a rational strategy to treat type 2 diabetes.

Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes.

We recently demonstrated that squalene synthase (SQS) inhibitors reduce plasma triglyceride through an LDL receptor-independent mechanism in Watanabe heritable hyperlipidemic rabbits (Hiyoshi et al. 2001. Eur.