padnarsertib

Padnarsertib is an orally available, small-molecule dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) being developed primarily as an antineoplastic agent. By inhibiting PAK4, a serine/threonine kinase implicated in cytoskeletal organization, survival signaling, and oncogenic pathways such as AKT and β-catenin, and simultaneously blocking NAMPT, the rate-limiting enzyme in the NAD+ salvage pathway, padnarsertib disrupts tumor cell metabolism and survival signaling, leading to decreased NAD+ levels and inhibition of downstream effectors including S6 ribosomal protein, AKT, and β-catenin.[6][8] Preclinical studies have shown antitumor activity across multiple solid and hematologic malignancy models, including ovarian cancer and KRASG12C-driven tumors, and the drug has been evaluated in early-phase clinical trials for advanced solid tumors, relapsed or refractory acute myeloid leukemia, and non-Hodgkin lymphoma, although at least one Phase 1 AML study was suspended and some trials have been terminated.[6][8][12][15][16][17]

Other names

PAK4-IN-1PAK-4-IN-1PAK 4-IN-1