Novel Serine Protease Dipeptidyl Peptidase IV Inhibitor: Alogliptin

Author(s): Ritesh Agrawal, Radhe Shyam Bahare, Pratima Jain, Subodh Narayan Dikshit, Swastika Ganguly

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 12 , Issue 13 , 2012

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Alogliptin (codenamed SYR-322) is a recently approved anti-diabetic drug in Japan, which has been under clinical development phase III in USA and Europe. Alogliptin has been developed by Takeda under the brand name “Nesina”. Alogliptin is a highly selective (> 10,000-time selectivity, potent, reversible and durable serine protease dipeptidyl peptidase IV enzyme is compared to DPP-8 and DPP-9) inhibitor, which has been developed as an alternative second-line to metformin in place of a sulphonylurea. Alogliptin has been observed to increase and prolong the action of incretin hormone by inhibiting the DPP-IV enzyme activity. Alogliptin has been observed to well absorb and show low plasma protein binding, which displays slow-binding properties to DPP-IV enzyme. The X-ray crystallography studies have been revealed that Alogliptin binds to DPP-IV active site by non-covalently and provides sustained reduction of plasma DPP-IV activity as well as lowering of blood glucose, in drug-naive patients with T2DM and inadequate glycemic control, once daily oral dosing regimen with varying levels of doses ranging from 25-800 mg. Alogliptin is approved as monotherapy and in combination with alpha-glucosidase & thiazolidinediones. The 26 week clinical study of Alogliptin revealed that Alogliptin doesn’t increase the weight and well tolerated. In the present review, we have tried to cover biology of DPP-IV, molecular chemistry, chemical characterization, crystal polymorphic information, interaction studies, commercial synthesis, current patent status, adverse effects and clinical status of Alogliptin giving emphasis on the medicinal chemistry aspect.

Keywords: Alogliptin, Approval, Diabetes Type-II, Dipeptidyl Peptidase-IV, DDP-IV, DPP-IV Inhibitor, Emerging Target, GIP, Gliptins, GLP-1, Glucagon-like peptide, Incretin, NESINA, Non-Insulin-Dependent Diabetes Mellitus (NIDDM), SYR-322, Takeda

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Article Details

Year: 2012
Page: [1345 - 1358]
Pages: 14
DOI: 10.2174/13895575112091345
Price: $65

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