JS-K (CAS 205432-12-8)

JS-K is an antiproliferative compound that acts as a nitric oxide (NO) donor by reacting with glutathione to release NO under physiological pH conditions. Its inhibitory effects on cell proliferation have been observed in various cell lines, including HL-60 cells (IC50 = 0.5 µM). The inhibitory activity of JS-K on HL-60 cell proliferation can be reversed by N-acetyl-L-cysteine, a precursor of glutathione. Furthermore, JS-K has demonstrated growth-inhibitory effects on solid tumor cell lines such as PPC-1, DLD-1, and Meth A. In an HL-60 mouse xenograft model, treatment with JS-K at a dose of 4 µmol/kg, i.v., three times per week resulted in a remarkable reduction of tumor volume by over 50%. Additionally, JS-K exhibits a range of effects on Jurkat T acute lymphoblastic leukemia cells, including inhibition of proliferation, induction of apoptosis, and disruption of the cell cycle. A noteworthy mechanism of action of JS-K involves the S-nitrosylation and subsequent degradation of β-catenin. It induces S-nitrosylation of β-catenin, leading to a dose-dependent reduction in nuclear β-catenin levels. Overall, JS-K functions as an antiproliferative agent through its role as a nitric oxide donor, displaying inhibitory effects on cell proliferation and tumor growth in various models. Additionally, it exerts diverse cellular effects, including apoptosis induction, cell cycle disruption, and modulation of β-catenin levels through S-nitrosylation.