Structured around development of new anti-cancer therapeutics, the lead compound of JSK Therapeutics (JSKT) is a first-in--class nitric oxide (NO)-generating compound of the arylated diazeniumdiolate class. Work undertaken by 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 Ewingâs sarcoma - 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.
