kb-NB184-43

kb-NB184-43 is a small molecule inhibitor of protein kinase D (PKD), a family of serine/threonine kinases involved in cell proliferation and survival, particularly in prostate and pancreatic cancers. Developed as a methoxy-analogue of kb-NB142-70, kb-NB184-43 was designed to improve pharmacokinetic properties. In preclinical studies conducted at the University of Pittsburgh Cancer Institute, the compound demonstrated in vitro cytotoxicity against Pc 3 prostate cancer and Panc-1 pancreatic cancer cells. In vivo evaluation in SCID mice bearing human cancer xenografts showed that kb-NB184-43 has a plasma half-life of approximately 14 minutes and undergoes extensive metabolism via oxidation and glucuronidation, resulting in more than 10 metabolites. Peak tumor concentrations in these models were found to be in the same order of magnitude as the concentrations required for in vitro cytotoxicity.