Discovery of a novel binding pocket in PPARγ for partial agonists: structure-based virtual screening identifies ginsenoside Rg5 as a partial agonist promoting beige adipogenesis DOI Creative Commons
Zhen Wang,

Kexin Shui,

Zehui Zhang

и другие.

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Май 8, 2025

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key target for metabolic disorders that contribute to obesity and type 2 diabetes mellitus (T2DM). However, full agonists such as thiazolidinediones (TZDs) have limitations in terms of side effects. Selective PPARγ modulators (SPPARγMs) alternative binding pockets offer the potential safer partial agonists. Here, we employed six computational algorithms (Fpocket, DeepSite, CavityPlus, DoGSiteScorer, CASTpFold, POCASA) identify novel allosteric pocket (pocket 6-5) ligand-binding domain (LBD), localized at helix 3 (H3), (H2), 2'(H2'), β-sheet interface. A virtual screening 4,097 natural compounds from traditional Chinese medicine (TCM) libraries was conducted, which led identification ginsenoside Rg5 (TWSZ-5) top hit. Molecular docking molecular dynamics (MD) revealed TWSZ-5 stabilizes 6-5 through hydrogen bonds with Ser342, Gln345, Lys261, Lys263. promoted beige adipocyte differentiation adipose-derived stem cells (ADSCs) vitro, upregulating Ucp1, Prdm16, Cpt1α, Pgc1α. The present study identifies SPPARγM utilizes an enhance thermogenesis while mitigating adverse These findings emphasize TCM derivatives structure-based strategies develop antidiabetic therapies precision pharmacology.

Язык: Английский

Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies DOI
Hao Chen, Yang Zhou, Haiping Hao

и другие.

Chinese Journal of Natural Medicines, Год журнала: 2024, Номер 22(8), С. 724 - 745

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

5
Discovery of a novel binding pocket in PPARγ for partial agonists: structure-based virtual screening identifies ginsenoside Rg5 as a partial agonist promoting beige adipogenesis DOI Creative Commons
Zhen Wang,

Kexin Shui,

Zehui Zhang

и другие.

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Май 8, 2025

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key target for metabolic disorders that contribute to obesity and type 2 diabetes mellitus (T2DM). However, full agonists such as thiazolidinediones (TZDs) have limitations in terms of side effects. Selective PPARγ modulators (SPPARγMs) alternative binding pockets offer the potential safer partial agonists. Here, we employed six computational algorithms (Fpocket, DeepSite, CavityPlus, DoGSiteScorer, CASTpFold, POCASA) identify novel allosteric pocket (pocket 6-5) ligand-binding domain (LBD), localized at helix 3 (H3), (H2), 2'(H2'), β-sheet interface. A virtual screening 4,097 natural compounds from traditional Chinese medicine (TCM) libraries was conducted, which led identification ginsenoside Rg5 (TWSZ-5) top hit. Molecular docking molecular dynamics (MD) revealed TWSZ-5 stabilizes 6-5 through hydrogen bonds with Ser342, Gln345, Lys261, Lys263. promoted beige adipocyte differentiation adipose-derived stem cells (ADSCs) vitro, upregulating Ucp1, Prdm16, Cpt1α, Pgc1α. The present study identifies SPPARγM utilizes an enhance thermogenesis while mitigating adverse These findings emphasize TCM derivatives structure-based strategies develop antidiabetic therapies precision pharmacology.

Язык: Английский

Процитировано

0