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

The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research DOI Creative Commons
Natalia G. Vallianou, Μaria Dalamaga,

Argyro Pavlou

и другие.

Biomolecules, Год журнала: 2025, Номер 15(5), С. 653 - 653

Опубликована: Май 1, 2025

Nanotechnology refers to the science that modulates molecules nanoscale dimension. Nanomedicine, i.e., utilization of nanotechnology for diagnosing and treating several disorders, is a subject ongoing research. The concept behind nanomedicine in diabetes mellitus (DM) treatment stems from need ameliorate absorption distribution antidiabetic therapies order overcome barriers, namely pH throughout gastrointestinal tract, gut microbiota, temperature/heat difficulties incorporation drugs into cells. Thus, scope particularly challenging demanding, considering fact human body perpetually changing entity achieve homeostasis. In this review, we will delve various nanoparticles are being studied terms treatment, their pros cons expanding knowledge field. Despite seems be very promising, there still many gaps our understanding how addresses its utilization. Moreover, high costs, along with an as-yet unclear safety profile, remain significant barrier widespread adoption. describe both phytochemicals chemical compounds seeks exploit pave way more efficacious comprehensive management mellitus.

Язык: Английский

Процитировано

0
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