國家衛生研究院 NHRI:Item 3990099045/5598

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Title:	Current advances and therapeutic potential of agents targeting dipeptidyl peptidases-IV, -II, 8/9 and fibroblast activation protein
Authors:	Chen, SJ;Jiaang, WT
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Dipeptidyl peptidase-IV (DPP-IV), a serine protease that specifically cleaves the N-terminal dipeptide with a preference for L-proline or L-alanine at the penultimate position, is involved in the degradation of incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 regulates glucose homeostasis by stimulating insulin secretion, inhibiting glucagon release, and delaying gastric emptying. Intravenous GLP-1 has been shown to increase insulin secretion in response to elevated glucose levels and offers therapeutic benefit for patients with type 2 diabetes. However, the therapeutic application of GLP-1 is severely compromised by its lack of oral activity and its rapid degradation by plasma DPP-IV. Consequently, small-molecule DPP-IV inhibitors that could extend the duration of action of GLP-1 and prolong its beneficial effects have been investigated as potential therapeutics for type 2 diabetes. This review summarizes important structural classes of DPP-IV inhibitors, focusing mainly on their inhibitory potency and selectivity for DPP-IV over other related peptidases such as DPP-II, DPP8, DPP9, and FAP. Because inhibition of DPP8 and/or DPP9 has been shown to cause severe toxicity in preclinical species, high selectivity is an important criterion in selecting DPP-IV inhibitors for clinical development. As of today, several DPP-IV inhibitors have completed phase III clinical studies for the treatment of type 2 diabetes. A brief overview of clinical efficacy data on these inhibitor drugs is provided here. In addition, biological activities of other related dipeptidyl peptidases (DPP-II, DPP8, DPP9, and FAP) will be summarized. Selective inhibitors for these peptidases and their therapeutic potential will be discussed.
Date:	2011-06
Relation:	Current Topics In Medicinal Chemistry. 2011 Jun;(11):1447-1463.
Link to:	http://dx.doi.org/10.2174/156802611795860933
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1568-0266&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000291636800004
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79960010822
Appears in Collections:	[Weir-Torn Jiaang] Periodical Articles [Shu-Jung Chen(1998-2001)] Periodical Articles

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