Designing Poly-agonists for Treatment of Metabolic Diseases: Challenges and Opportunities

Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation

“…1 ). Despite their close evolutionary relationship, the major actions of these hormones are non-overlapping, covering the regulation of glucose homeostasis, appetite, and maintaining the proper function of intestines 18 , 19 . Their synthetic derivatives are successfully applied in the therapy of glucose metabolism-related disorders, with growing interest in further indications 20 .…”

Discovery of Cobimetinib as a novel A-FABP inhibitor using machine learning and molecular docking-based virtual screening

“…Over the past two decades, there has been a dramatic increase in research and development expenditures on drugs for the treatment of metabolic and related cardiovascular and cerebrovascular diseases. 45,46 With the progress of computer-aided drug design technology, the application of machine learning and molecular docking in drug development has increased rapidly. Machine learning integrates massive data resources to solve biomedical problems with the combination of computer science and statistics and has the ability to deal with large and complex data.…”

The Design and Optimization of Monomeric Multitarget Peptides for the Treatment of Multifactorial Diseases

“…Therefore, despite the considerable risks and financial costs, bariatric surgery has become the most effective method to significantly reduce weight and improve metabolic control. − In recent years, GLP-1R agonists have been discovered that deliver a meaningful and sustained effect on obesity. , Liraglutide and semaglutide represent the registered peptide-based drugs for weight loss to date. However, GLP-1R agonists are usually dose-limited by gastrointestinal adverse events, which reduce the maximal efficacy and require sequential dose escalation. , The preclinical results of the drug combination using GLP-1R agonists and other hormone drugs indicate that, based on the synergistic effect produced by more than one mechanism of action, they may achieve clinical effects similar to those achieved by bariatric surgery. − In view of the established advantages of GLP-1 in glycemic control, body weight, and cardiovascular risk, GLP-1 has become the “anchor hormone” in combination approaches that seek additional mechanisms to supplement and potentiate GLP-1R agonism. Gastric inhibitory peptide (GIP) and GCG, as compatible, nonredundant partners of GLP-1, are candidates for multitarget unimolecular peptides.…”