PD-1/PD-L1-IN-9 hydrochloride is a potent and orally active inhibitor of PD-1/PD-L1 interaction, with an IC50 of 3.8 nM. PD-1/PD-L1-IN-9 hydrochloride can enhance the killing activity of tumor cells by immune cells. PD-1/PD-L1-IN-9 hydrochloride also exhibits significant in vivo antitumor activity in a CT26 mouse model[1].
PD-1/PD-L1-IN-9 盐酸盐(compound 24) (46.9-1500 nM; 预处理 2 h) 剂量依赖性地激活外周血单核细胞 (PBMCs) 对 MDB-MB 231 细胞的抗肿瘤免疫，EC50 约为 100 nM[1]。
PD-1/PD-L1-IN-9 盐酸盐 (化合物24) (40-80 mg/kg; 口服; 每天一次，持续 2 周) 以剂量依赖的方式抑制肿瘤生长，并且不会导致小鼠体重减轻或死亡[1]。
PD-1/PD-L1-IN-9 盐酸盐 (3 mg/kg; 静脉注射; 单次剂量) 在大鼠中的半衰期 T1/2=4.2 h、血浆清除率 Cl=11.5 L/h/kg，Cmax=1233 ng/mL[1]。
PD-1/PD-L1-IN-9 盐酸盐 (25 mg/kg; 口服; 单次剂量) 在大鼠中表现出中等的口服生物利用度 (F= 22%)、半衰期 (t1/2=6.4 h)，和 Cmax (=192 ng/mL)[1]。
| Animal Model: | Male BALB/c mice (5-6 weeks) were inoculated CT26 cells[1] |
| Dosage: | 40 mg/kg, 80 mg/kg |
| Administration: | Oral gavage; once daily, for 2 weeks |
| Result: | Significantly decreased the final tumor weight, with TGI values of 60 and 67% at the dose of 40 and 80 mg/kg, respectively. |
| Animal Model: | Pharmacokinetic analysis in sprague-Dawley (SD) rats[1] | |||||||||||||||||||||||||||
| Dosage: | 3 mg/kg and 25 mg/kg | |||||||||||||||||||||||||||
| Administration: | Intravenous injection or oral gavage; single dose | |||||||||||||||||||||||||||
| Result: |
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[1]. Wang T, et, al. Novel Biphenyl Pyridines as Potent Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction. J Med Chem. 2021 May 30.