Abstract
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
Mini-Reviews in Medicinal Chemistry
Title:Novel Serine Protease Dipeptidyl Peptidase IV Inhibitor: Alogliptin
Volume: 12 Issue: 13
Author(s): Ritesh Agrawal, Radhe Shyam Bahare, Pratima Jain, Subodh Narayan Dikshit and Swastika Ganguly
Affiliation:
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
Abstract: 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.
Export Options
About this article
Cite this article as:
Agrawal Ritesh, Shyam Bahare Radhe, Jain Pratima, Narayan Dikshit Subodh and Ganguly Swastika, Novel Serine Protease Dipeptidyl Peptidase IV Inhibitor: Alogliptin, Mini-Reviews in Medicinal Chemistry 2012; 12 (13) . https://dx.doi.org/10.2174/13895575112091345
DOI https://dx.doi.org/10.2174/13895575112091345 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Editorial (Hot Topic :Incretins: Novel Cardiovascular Protection Agents)
Cardiovascular & Hematological Agents in Medicinal Chemistry Evaluation of the Antioxidant and Antidiabetic Potential of the Poly Herbal Formulation: Identification of Bioactive Factors
Cardiovascular & Hematological Agents in Medicinal Chemistry Drug Combinations for Dyslipidemia and Obesity Treatment in Metabolic Syndrome
Current Pharmaceutical Design Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease
Current Topics in Medicinal Chemistry α-Glucosidase Inhibitory Activity of the Extracts and Major Phytochemical Components of Smilax glabra Roxb
The Natural Products Journal A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial
Recent Patents on Inflammation & Allergy Drug Discovery Treatment of Cardiovascular Risk Factors in Women
Current Medicinal Chemistry Editorial [Hot Topic:Dietary Determinants of the Metabolic Syndrome (Guest Editor: Luc Tappy Co-Editors: Jacques Delarue and Kim-Anne Le)]
Current Nutrition & Food Science Mesenchymal Stem Cell-Based Therapy for the Treatment of Type 1 Diabetes Mellitus
Current Stem Cell Research & Therapy Complex Obesity
Current Pediatric Reviews Long-term Reproductive and Metabolic Consequences of PCOS
Current Diabetes Reviews Potential of Gentiana lutea for the Treatment of Obesity-associated Diseases
Current Pharmaceutical Design Interleukin-25: Key Regulator of Inflammatory and Autoimmune Diseases
Current Pharmaceutical Design Targeting Adenosine Signaling to Treatment of Diabetic Nephropathy
Current Drug Targets A Review of the Hypoglycemic Effects of Five Commonly Used Herbal Food Supplements
Recent Patents on Food, Nutrition & Agriculture Clinical View on the Need to Develop New Anti-Diabetic Drugs
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Practical Recommendations for Familial Combined Hyperlipidemia Diagnosis and Management: An Update
Vascular Disease Prevention (Discontinued) Phase 4 Studies in Heart Failure - What is Done and What is Needed?
Current Cardiology Reviews The Action of Polyphenols in Diabetes Mellitus and Alzheimer's Disease: A Common Agent for Overlapping Pathologies
Current Neuropharmacology Mechanisms of the Blunting of the Sympatho-Adrenal Response: A Theory
Current Diabetes Reviews