JCS-1 is a potent DcpSPROTAC degrader. It non-covalently binds to DcpS via an RG3039-based warhead and recruits the E3 ligase VHL. JCS-1 facilitates the ubiquitination and degradation of DcpS at nanomolar concentrations, with a DC50 of 87 nM in MOLM-14 cells. This compound can be utilized in research on acute myeloid leukemia and other DcpS-dependent genetic disorders.

化合物JCS-1在MOLM-14细胞中以剂量依赖性方式降解DcpS，其DC50为87 nM（0.1-10000 nM, 24 h）。在1 μM浓度下，JCS-1快速且持续地降解MOLM-14细胞中的DcpS，处理后2小时内迅速发生降解，最大降解在12到24小时之间。此外，JCS-1（1 μM, 每3天一次，共12天）抑制MOLM-14细胞的增殖和活力，IC50值为1.1 μM。在1 μM 6小时的处理下，JCS-1改变MOLM-14细胞的mRNA库，显著增加SNORD99和DDX24的表达。内切酶抑制剂MLN4924和蛋白酶体抑制剂Epoxomicin能够抑制由JCS-1引起的降解。