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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

In Search of Novel SGLT2 Inhibitors by High-throughput Virtual Screening

Author(s): Abhijit Debnath*, Shalini Sharma, Rupa Mazumder, Avijit Mazumder, Rajesh Singh, Ankit Kumar, Arpita Dua, Priya Singhal, Arvind Kumar and Gurvinder Singh

Volume 21, Issue 3, 2024

Published on: 01 December, 2023

Article ID: e011223224135 Pages: 12

DOI: 10.2174/0115701638267615231123160650

Price: $65

Abstract

Background: Type 2 diabetes mellitus constitutes approximately 90% of all reported forms of diabetes mellitus. Insulin resistance characterizes this manifestation of diabetes. The prevalence of this condition is commonly observed in patients aged 45 and above; however, there is an emerging pattern of younger cohorts receiving diagnoses primarily attributed to lifestyle-related variables, including obesity, sedentary behavior, and poor dietary choices. The enzyme SGLT2 exerts a negative regulatory effect on insulin signaling pathways, resulting in the development of insulin resistance and subsequent elevation of blood glucose levels. The maintenance of glucose homeostasis relies on the proper functioning of insulin signaling pathways, while disruptions in insulin signaling can contribute to the development of type 2 diabetes.

Objective: Our study aimed to identify novel SGLT2 inhibitors by high-throughput virtual Screening.

Methods: We screened the May bridge Hit Discover database to identify potent hits followed by druglikeness, synthetic accessibility, PAINS alert, toxicity estimation, ADME assessment, and consensus molecular docking.

Results: The screening process led to the identification of three molecules that demonstrated significant binding affinity, favorable drug-like properties, effective ADME, and minimal toxicity.

Conclusion: The identified molecules could manage T2DM effectively by inhibiting SGLT2, providing a promising avenue for future therapeutic strategies.

Graphical Abstract

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