Antidiabetic Molecular Targets: Updates on Old and Emerging Targets and their Small Molecule Modulators

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Background

The global prevalence of diabetes has increased incessantly by almost 70% over the past few years; hence, this metabolic disease now ranks as the 9th leading cause of death worldwide. The International Diabetes Federation reported that in 2019, around 463 million people had diabetes, with approximately 4.2 million people dying from diabetes-related complications. The total number of diabetes patients is projected to rise to 700 million people by 2045. The increasing knowledge and understanding of underlying molecular mechanisms of blood glucose level dysregulation has continuously unearthed druggable molecular targets relevant for managing type-2 diabetes mellitus (T2DM) – the more commonly diagnosed type of the disease. Hitherto, targets such as sodium-glucose co-transporter-2 (SGLT-2), dipeptidyl peptidase-4 (DPP-IV), glucagon receptor (GCGr), peroxisome proliferator-activated receptor-γ (PPARγ), and α-glucosidase have been studied extensively with clinic-worthy drug candidates emerging from such exploits. 

Many adverse side effects, particularly urinary infections, nephrotoxicity, hypoglycemia, and weight gain have become increasingly associated with usage of existing antidiabetic agents, thus precipitating the urgency for new drugs and the discovery of new molecular targets with reduced adverse effects. Therefore, this Research Topic's primary goal is to bring together researchers' contributions directed at new natural or synthetic compounds that effectively modulate molecular targets and, consequently, regulate blood glucose level. Works describing new molecular targets and their modulation, thus validating the identified target's therapeutic relevance are also welcomed.

This Research Topic encompasses Original Research, full and mini-Reviews, and Perspectives covering the following specific areas:

 • Design and synthesis of novel antidiabetic agents, and their evaluation against new or existing targets.
 • Identification and structure-activity-relationship analysis of new molecular assemblies in relation to their biological activities.
 • High-throughput virtual screening with experimental validation of promising compounds
 • Total synthesis of natural products, their derivatives, and their biological evaluation
 • Detailed in vivo evaluation of new or existing antidiabetic agents in combination therapy

Please note that biological evaluation implies antidiabetic efficacy, inhibition/binding studies, and toxicity evaluation. Additionally, basic molecular modeling studies without experimental validation do not fall into the Research Topic's scope.

Keywords: Diabetes, molecular targets, drug discovery, structure-based drug design

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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