Abstract
In India as well as globally, diabetes is in a state of high risk and next to cardiovascular disease. As per the WHO, the risk of diabetes is expected to rise about 511 million by 2030. In quest of novel targets for type-2 diabetes, many targets were elucidated, such as Glycogen Synthase Kinase-3 (GSK-3), Dipeptidyl Peptidase (DPP-IV), PPAR-γ, α-Glucosidase, α-Amylase, GLP-1, and SGLT. Among the targets, GSK-3 was reported to be an effective target for the treatment of diabetes. In the metabolism of glycogen, GSK is a regulatory enzyme for the biosynthesis of glycogen (glycogenesis). It catalyzes the synthesis of a linear unbranched molecule with 1,4-α-glycosidic linkages. GSK-3 family has two isoenzymes, namely α and β, which differ in their Nand C- terminal sequences and are semi-conservative multifunctional serine/threonine kinase enzymes. In this chapter, we discuss an overview of general diabetic mechanisms and how GSK-3 modulation may influence these processes. Mutation in the GSK-3 complex causes diabetes. Synthetic and natural scaffolds modulate GSK-3 against diabetes and leading to its optimization for the development of GSK-3 inhibitors. This review mainly focuses on the development of GSK-3 inhibitors and highlights current and potential future therapeutic approaches that support the notion of targeting glucose metabolism with novel antidiabetic agents.
Keywords: Diabetes, Target, GSK-3, lead optimization, GSK-3β inhibitors, glucose metabolism.
Current Drug Targets
Title:GSK-3 Inhibitors as New Leads to Treat Type-II Diabetes
Volume: 22 Issue: 13
Author(s): Gowru Srivani, Ramyakrishna Sharvirala, Prabhakar Reddy Veerareddy, Dilipkumar Pal and Gangarapu Kiran*
Affiliation:
- School of Pharmacy, Anurag Group of Institutions, Hyderabad-500 088, Telangana,India
Keywords: Diabetes, Target, GSK-3, lead optimization, GSK-3β inhibitors, glucose metabolism.
Abstract: In India as well as globally, diabetes is in a state of high risk and next to cardiovascular disease. As per the WHO, the risk of diabetes is expected to rise about 511 million by 2030. In quest of novel targets for type-2 diabetes, many targets were elucidated, such as Glycogen Synthase Kinase-3 (GSK-3), Dipeptidyl Peptidase (DPP-IV), PPAR-γ, α-Glucosidase, α-Amylase, GLP-1, and SGLT. Among the targets, GSK-3 was reported to be an effective target for the treatment of diabetes. In the metabolism of glycogen, GSK is a regulatory enzyme for the biosynthesis of glycogen (glycogenesis). It catalyzes the synthesis of a linear unbranched molecule with 1,4-α-glycosidic linkages. GSK-3 family has two isoenzymes, namely α and β, which differ in their Nand C- terminal sequences and are semi-conservative multifunctional serine/threonine kinase enzymes. In this chapter, we discuss an overview of general diabetic mechanisms and how GSK-3 modulation may influence these processes. Mutation in the GSK-3 complex causes diabetes. Synthetic and natural scaffolds modulate GSK-3 against diabetes and leading to its optimization for the development of GSK-3 inhibitors. This review mainly focuses on the development of GSK-3 inhibitors and highlights current and potential future therapeutic approaches that support the notion of targeting glucose metabolism with novel antidiabetic agents.
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Cite this article as:
Srivani Gowru , Sharvirala Ramyakrishna , Veerareddy Reddy Prabhakar , Pal Dilipkumar and Kiran Gangarapu*, GSK-3 Inhibitors as New Leads to Treat Type-II Diabetes, Current Drug Targets 2021; 22 (13) . https://dx.doi.org/10.2174/1389450122666210120144428
DOI https://dx.doi.org/10.2174/1389450122666210120144428 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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