JSK Therapeutics (JSKT) was founded in 2008 in order to develop new anti-cancer therapeutics. The lead compound that JSKT will bring to market is JS-K, a first-in- class nitric oxide (NO)-generating compound of the arylated diazeniumdiolate class. JS-K was developed through collaboration between the team of Dr. Larry Keefer at the National Cancer Institute (NCI) and Dr. Paul Shami’s laboratory at the University of Utah. JS-K has shown single agent activity in animal models of acute myeloid leukemia (AML), multiple myeloma (MM), non-small cell lung cancer, hepatocellular carcinoma, prostate cancer, glioma and Ewing’s sarcoma. JS-K was also shown to inhibit metastasis development in an orthotopic renal cell carcinoma model. JS-K has synergistic activity with cytarabine against AML and synergistic activity with bortezomib against MM.
Besides its direct cytotoxic effects, JS-K is a potent inhibitor of tumor angiogenesis. It also inhibits the interaction between MM cells and the bone marrow microenvironment. Mechanistically, JS-K impairs the redox state of malignant cells by depleting intracellular glutathione, a critical tripeptide cellular antioxidant. JS-K could also sensitize MM cells to the cytotoxic effects of immune effector cells. Using nanoparticles, the Shami laboratory has developed a formulation for JS-K. JS-K was well tolerated without induction of hypotension in a dog toxicology study. The FDA has granted orphan drug designation for JS-K for the indications of AML and MM, which are the initial target diseases for the development of JS-K. JS-K is a new chemical entity that could constitute a paradigm shift in cancer therapy.