Padnarsertib (KPT-9274) is an orally bioavailable inhibitor targeting both PAK4 and Nicotinamide phosphoribosyltransferase (Nampt), with IC50 values of <100 nM and 120 nM, respectively [1][2][3].
体内研究
Padnarsertib shows a reduction in xenograft growth similar to that of Sunitinib. Minimal effects of Padnarsertib are observed on normal human RPTECs, with no apparent toxicity in vivo[2].
Padnarsertib is currently undergoing evaluation in a phase I clinical trial involving patients with advanced solid malignancies and NHL [2].
Padnarsertib (oral administation; 100mg/kg or 200 mg/kg; twice a day; 14 days) exhibits a reduction in xenograft growth without significant weight loss. Plasma and tumor concentrations of Padnarsertib, measured 8 hours after the end of the experiment, are 10757 ng/mL and 10647 ng/mL, respectively [3].
体外研究
Padnarsertib diminishes the PAK4/β-catenin pathway, leading to NAD depletion and reducing viability, invasion, and migration in various RCC cell lines. In a cell-free enzymatic assay utilizing recombinant NAMPT, Padnarsertib exhibits an IC50 of approximately 120 nM. Additionally, Padnarsertib retards G2–M transit and triggers apoptosis in RCC cell lines [2].
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