KPT-9274 is a first-in-class orally bioavailable small molecule targeting two proteins that could play an important role in cancer development: PAK4 and NAMPT.
PAK4 is member of the PAK family of kinases that includes 6 proteins, PAK1-6. PAK4 is a signaling protein regulating numerous fundamental cellular processes, including intracellular transport, cellular division, cell shape and motility, cell survival, immune defense and the development of cancer. PAK4 interacts with many key signaling molecules involved in cancer such as beta-catenin, CDC42, Raf-1, BAD and myosin light chain.
NAMPT (Nicotinamide phosphoribosyltransferase; also known as PBEF or Visfatin) is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor, and hormone that can be found in complex with PAK4 in the cell. NAMPT is of interest as an oncology target because it catalyzes the rate-limiting step in one of the two intracellular salvage pathways that generate nicotinamide adenine dinucleotide, or NAD. NAD is a universal energy- and signal-carrying molecule involved in mitochondrial function, energy metabolism, calcium homeostasis, antioxidation, and paradoxically generation of oxidative stress, gene expression, immunological functions, aging, and cell death.
Co-inhibition of PAK4 and NAMPT may lead to synergistic anti-tumor effects through energy depletion, inhibition of DNA repair, cell cycle arrest, inhibition of proliferation, and ultimately apoptosis. Hematologic and solid tumor cells that have become dependent on both PAK4 and NAMPT pathways may be susceptible to single-agent cytotoxicity by KPT-9274.
KPT-9274 is an investigational medicine and has not been approved by The United States Food and Drug Administration (FDA), Health Canada, the European Medicines Agency (EMA), nor any other regulatory agency.
To learn more about our Phase 1 study with KPT-9274, titled A Phase 1 Open-Label Study of the Safety, Tolerability and Efficacy of KPT-9274, a Dual Inhibitor of PAK4 and NAMPT, in Patients With Advanced Solid Malignancies please visit clinicaltrials.gov