Speaker
Description
The protein tyrosine phosphatase 1B (PTP1B; EC 3.1.3.48), encoded by the PTPN1 gene, dephosphorylates the activated insulin receptor and IRS-1, acting as a negative regulator of insulin and leptin. PTP1B knockout mice, which are more insulin sensitive and resistant to diet-induced obesity, genetically validate PTP1B as a dual target for type 2 diabetes and obesity. However, no inhibitor has made it to clinical trials. We applied an integrated and phased flow, with prior validation, to the 53 phenolic compounds of Lemna minor, found in literature and hosted in the LMW Database against PTP1B (PDB 2QBS): (1) validation by redocking of the co-crystallized inhibitor; (2) molecular docking (AutoDock Vina) [4]; (3) consensus by second scoring function (Vinardo) and by machine learning (RF-Score); (4) AI co-folding with confidence metric (Boltz-2); and (5) internal control with cross-validation in the literature. Lemna minor was rich in PTP1B ligands (about two-thirds of the phenolics showed a strong predicted interaction). Flavone luteolin stood out as a lead in all criteria (docking −9.14 kcal/mol; best flavonoid by affinity; ipTM 0.90), corroborated by literature: luteolin derivatives inhibit PTP1B (luteolin-7-diglucuronide, IC50 = 2.10 μM); quercetin is a reference inhibitor of aldose reductase (IC50 = 6.6 μM); and apigenin inhibits α-glucosidase (IC50 = 10.5 μM). Lemna minor extracts emerge as multi-component, multitarget antidiabetic candidates, with a solid basis for subsequent in vitro experimental confirmation.
Keywords
Extract;PTP1B;luteolin;flavonoids;diabetes;docking
References
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| Corresponding author email | felipemacedo.alves20@gmail.com |
|---|---|
| Scientific Session | Applications |
