OY-101

OY-101 is an orally active, potent and specific P-glycoprotein (P-gp) inhibitor. OY-101 can sensitize drug-resistant tumors and effectively reverse tumor multidrug resistance. OY-101 is improvements in water-solubility, cytotoxicity, and reversal activity compared to Tetrandrine (HY-13764)[1].

Research Areas >> Cancer

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

OY-101 与Vincristine (HY-N0488A) 对耐药细胞 Eca109/VCR 表现出优异的协同抗癌作用，IC50 为 9.9 ± 1.3 nM< sup>[1]。 OY-101 (0-5 μM) 对 Eca109/VCR 细胞没有显著毒性，并且在 Eca109/VCR 细胞中表现出显着增加的Vincristine (HY-N0488A) 敏感性[1]。 Cell Viability Assay[1] Cell Line: Eca109/VCR cells Concentration: 1.0, 2.5, and 5.0 μM Incubation Time: 48 h Result: Exhibited significantly increased Vincristine sensitization in Eca109/VCR cells, achieving around 3.7, 103.4, and 690.6-fold reversal activity, respectively.

OY-101 (30 mg/kg/2 天，灌胃，持续 3 周)增加体内对长春新碱 (HY-N0488A) 的致敏性，且无明显毒性[1]。 OY-101 (静脉给药 (3 mg/kg) 和口服给药 (30 mg/kg)；一次) 表现出良好的药代动力学[1]。 Animal Model: Female nude mice (4-5 weeks old, xenograft model bearing P-gp-overexpressing Eca109/VCR cells)[1] Dosage: 30 mg/kg Administration: IG, once every 2 days, for 3 weeks, 1 h before tail vein injection of Vincristine (HY-N0488A) Result: Only co-administration OY-101 with Vincristine can effectively inhibit tumor proliferation in vivo (P < 0.001) and significantly reduce tumor weight. After 3 weeks of treatment, the tumor growth inhibition rate of the OY-101/Vincristine combination was 79.13%, which was significantly lower than that of the single-treatment group and the vehicle group. Animal Model: SD rats (8 week-old, male, 300-400 g)[1] Dosage: 3 mg/kg (IV), 30 mg/kg (PO) Administration: Intravenous and oral administration, once (Pharmacokinetic Analysis) Result: Pharmacokinetic Parameters of OY-101 in male Sprague-Dawley rats[1]. IV (3 mg/kg) PO (30 mg/kg) Tmax (h) 0.17 ± 0.12 0.38 ± 0.18 Cmax (ng/mL) 1573.20 ± 143.97 636.55 ± 355.60 AUC0-t (ng/mL∗h) 2688.45 ± 180.10 2665.45 ± 450.92 t1/2 (h) 8.43 ± 7.83 7.37 ± 4.92 CL/F (L/kg/h) 1.10 ± 0.08 11.16 ± 2.10 Vz/F (L/kg) 12.84 ± 11.33 111.27 ± 56.82 F (%) 7.65 ± 2.15

[1]. Zeng R, et al. Simplified Derivatives of Tetrandrine as Potent and Specific P-gp Inhibitors to Reverse Multidrug Resistance in Cancer Chemotherapy. J Med Chem. 2023 Mar 23;66(6):4086-4105.