PD-1/PD-L1-IN-NP19

PD-1/PD-L1-IN-NP19 is a PD-1/PD-L1 inhibitor, with an IC 50 of 12.5 nM for human PD-1/PD-L1 interaction. PD-1/PD-L1-IN-NP19 could activate the immune microenvironment in tumor, which may contribute to its antitumor effects In Vitro PD-1/PD-L1-IN-NP19 (compound NP19) (0.37-10 μM; 72 h) significantly elevates the production of IFN-γ in a dose dependent manner from T cells co-cultured with tumor cells. PD-1/PD-L1-IN-NP19 exhibits much lower activity for inhibiting mouse PD-1/PD-L1 interaction with an IC 50 in the micromolar range (>1µM), as compared to the inhibition of human PD1/PD-L1 interaction (IC 50 =12.5 nM). PD-1/PD-L1-IN-NP19 (10 µM; 48 h) displays no apparent cytotoxic effects on A549, MCF-7, and B16-F10 cells at a concentration of 10 µM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo PD-1/PD-L1-IN-NP19 (compound NP19) (25-100 mg/kg; intragastric gavage once daily for 15 d) inhibits the growth of melanoma tumors dramatically in mice . PD-1/PD-L1-IN-NP19 (25 mg/kg; i.p. daily for 14 d) demonstrates significant antitumor efficacy with a tumor growth inhibition (TGI) of 76.5% and is well tolerated in an H22 hepatoma mouse model . PD-1/PD-L1-IN-NP19 (1 mg/kg; i.v.) shows the half time (t 1/2 =1.5±0.5 h), clearance rate (CL=0.9±0.2 L/h/kg) and apparent distribution volume (Vss=2.1±0.5 L/kg) in rats . PD-1/PD-L1-IN-NP19 (10 mg/kg; p.o.) shows the oral absorption (T max =0.6±0.2 h), long half-life (t 1/2 =10.9±7.7 h) and oral bioavailability (F=5%) in rats . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: BALB/c mice (6-8 weeks) with B16-F10 melanoma tumors Dosage: 25, 50, 100 mg/kg Administration: Intragastric gavage once daily for 15 days Result: Inhibited the growth of melanoma tumors up to 51.1, 75 and 80.9% at dose of 25, 50, 100 mg/kg, respectively. Exhibited normal physical activity and increased body weights slightly. Animal Model: Male Sprague-Dawley rats Dosage: 1 mg/kg for i.v. and 10 mg/kg for p.o. (Pharmacokinetic Analysis) Administration: I.v. and p.o. Result: I.v.: t 1/2 =1.5 h; C max =1751 μg/L; CL=0.9 L/h/kg. P.o.: t 1/2 =10.9 h; C max =69.5 μg/L; CL=23.1 L/h/kg. Form:Solid IC50& Target:IC50: 12.5 nM (human PD-1/PD-L1)

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