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  • Title: Sixteen-years of clinically relevant dipeptidyl peptidase-IV (DPP-IV) inhibitors for treatment of type-2 diabetes: a perspective.
    Author: Kushwaha RN, Haq W, Katti SB.
    Journal: Curr Med Chem; 2014; 21(35):4013-45. PubMed ID: 25245373.
    Abstract:
    Inhibition of DPP-IV enzyme has taken centre stage as a validated drug target for type 2 diabetes therapy and as a result of research efforts done towards developing effective DPP-IV inhibitors, the first clinical candidate of this class came in focus in 1998. Thus, from 1998 to 2013, these 16-years have witnessed heightened research activities in the discovery and development of clinically relevant inhibitors of DPP-IV as antidiabetic agents. The effective DPP-IV inhibitors have played a key role in this endeavour and as result there are eight approved gliptins in the clinical usage while others are in different stages of clinical trials. A wide variety of DPP-IV inhibitors were synthesized and evaluated; and were classified into several categories based on their core structural features. In this article, classification of all the clinically relevant DPP-IV inhibitors based on selectivity, clinical efficacy and safety profiles is reviewed in terms of generations. This review also encompasses clinical phase wise discussion, developmental progress, chemistry and binding modes of all clinical DPP-IV inhibitors. In addition, major challenges facing the future design and development of safe clinical DPP-IV inhibitor are also briefly mentioned.
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