HIV蛋白酶抑制剂

TargetValue HIV protease (Cell-free assay) 2 nM(Ki)

体内研究表明AG1343在多个物种口服后能很好地被吸收，在人类中具有良好的药代动力学特征。在饲养大鼠中，该化合物的口服生物利用度为43%，而在禁食大鼠中，口服生物利用度显著下降至29%。在多种生物体内，Nelfinavir的生物口服利用度为：犬类中47%、狨猴中17%、食蟹猴中26%。在口服后，其在血浆中半衰期较长，这可能是因为分解和吸收较慢的缘故。在人类中，Nelfinavir能很好地被吸收，尤其是随食物给药时，具有比较少、容易处理的副作用，安全性良好。

Nelfinavir (AG1341) Mesylate (1-10 μM; 48 hours) inhibits the proliferation of multiple myeloma cells. Nelfinavir Mesylate inhibits 26S chymotrypsin-like proteasome activity, impairs proliferation and triggers apoptosis of the myeloma cell lines and fresh plasma cells. Nelfinavir Mesylate (1-10 μM; 17 hours) induces apoptosis of multiple myeloma cell lines. Nelfinavir Mesylate (5 μM; 0-24 hours) decreases the phosphorylation of AKT. Nelfinavir Mesylate activates the cleavage of caspase-3, decreases the phosphorylation of AKT, STAT-3, ERK1/2, and activates the pro-apoptotic pathway of the unfolded protein response system. Cell Proliferation Assay Cell Line: RPMI, LP1, U266, OPM2 and MM1S cells Concentration: 1, 2, 5, 10 μM Incubation Time: 48 hours Result: Inhibited the proliferation of RPMI, LP1, U266, OPM2 and MM1S cell lines in a dose-dependent manner with an IC 50 of 1-5 μM. Apoptosis Analysis Cell Line: LP1 and U266 cells Concentration: 1-10 μM Incubation Time: 17 hours Result: Induced a dose-dependent increase in the percentage of annexin V + /propidium iodide + cells. Western Blot Analysis Cell Line: U266 cells Concentration: 5 μM Incubation Time: 0-24 hours Result: The level of AKT phosphorylation in U266 cells decreased.

Nelfinavir Mesylate (Viracept, AG1343) 是强效的HIV protease抑制剂，Ki为2 nM。