Identification of a novel PPARγ modulator with good anti-diabetic therapeutic index via structure-based screening, optimization and biological validation

Chen, Fangyuan; Ma, Lei; Cai, Guihui; Tang, Junyuan; Wang, Yi; Liu, Qingmei; Liu, Xiawen; Hou, Ning; Zhou, Zhi; Yi, Wei

doi:10.1016/j.biopha.2022.113653

Cited by 5 publications

(2 citation statements)

References 71 publications

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“…These differences in the cardiovascular clinical outcome between the two drugs can be attributed to their potency and selectivity for the PPARg receptor since PPARg partial agonists provide equivalent therapeutic benefits without the associated side effects. Consequently, there are efforts to develop selective PPARg modulators that will be both effective in alleviating hyperglycemia in T2D and safe [23].…”

Section: Thiazolidinedionesmentioning

confidence: 99%

The role of glucose in cardiac physiology and pathophysiology

Mylonas

Drosatos

Mia

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewHeart failure is one of the major causes of death worldwide and continues to increase despite therapeutics and pharmacology advances. Fatty acids and glucose are used as ATP-producing fuels in heart to meet its energy demands. However, dysregulation of metabolites’ use plays a pivotal role in cardiac diseases. How glucose becomes toxic or drives cardiac dysfunction is incompletely understood. In the present review, we summarize the recent findings on cardiac cellular and molecular events that are driven by glucose during pathologic conditions and potential therapeutic strategies to tackle hyperglycemia-mediated cardiac dysfunction.Recent findingsSeveral studies have emerged recently, demonstrating that excessive glucose utilization has been correlated with impairment of cellular metabolic homeostasis primarily driven by mitochondrial dysfunction and damage, oxidative stress, and abnormal redox signaling. This disturbance is associated with cardiac remodeling, hypertrophy, and systolic and diastolic dysfunction. Both human and animal heart failure studies, report that glucose is a preferable fuel at the expense of fatty acid oxidation during ischemia and hypertrophy, but the opposite happens in diabetic hearts, which warrants further investigation.SummaryA better understanding of glucose metabolism and its fate during distinct types of heart disease will contribute to developing novel therapeutic options for the prevention and treatment of heart failure.

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Section: Thiazolidinedionesmentioning

confidence: 99%

The role of glucose in cardiac physiology and pathophysiology

Mylonas

Drosatos

Mia

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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“…SPPARMs are a novel class of drugs that selectively activate specific PPAR target genes, lowering the likelihood of side effects. Several SPPARMs are now in development and may outperform TZDs in terms of efficacy and safety [49].…”

Section: Development Of Selective Pparγ Modulators (Spparγms)mentioning

confidence: 99%

Exploring the Potential Benefits and Risks of 2,4-Thiazolidinediones (TZDs) in the Management of Diabetes and Related Conditions

Kumari¹

2023

JPDD

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TZDs have been demonstrated to enhance insulin sensitivity and glucose absorption in muscle and adipose tissues, resulting in better glycemic control in type 2 diabetes patients. TZDs have also been demonstrated to have potential benefits in terms of lowering the risk of cardiovascular disease and improving lipid profiles. The potential benefits and hazards of a class of medications known as 2,4-thiazolidinediones (TZDs) in the treatment of diabetes and related disorders are discussed in this article. According to recent research, cardiovascular toxicity with rosiglitazone and a rise in bladder cancer with pioglitazone is no longer serious concerns. TZD use is also connected with major hazards, such as an increased risk of bone fractures, edema, and weight gain. Furthermore, TZDs have been linked to an increased risk of bladder cancer, and long-term use may result in liver damage. Overall, TZDs can be an effective tool in the treatment of diabetes and related disorders, but doctors must carefully balance the potential advantages with the hazards associated with their usage. Patients should be constantly monitored for side effects, and alternate treatment options should be sought when necessary.

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