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.

JCS-1 exhibits a dose-dependent degradation of DcpS in MOLM-14 cells with a DC50 of 87 nM across a range of 0.1 to 10000 nM over 24 hours. At a concentration of 1 μM, JCS-1 causes rapid and sustained degradation of DcpS within 2 hours of treatment, reaching maximum degradation between 12 and 24 hours. Furthermore, JCS-1 (1 μM, administered every 3 days for a total of 12 days) inhibits proliferation and reduces the viability of MOLM-14 cells, with an IC50 of 1.1 μM. Treatment with JCS-1 (1 μM for 6 hours) also affects the mRNA profile of MOLM-14 cells, notably increasing the expression of SNORD99 and DDX24. The degradation induced by JCS-1 can be inhibited by the endopeptidase inhibitor MLN4924 and the proteasome inhibitor Epoxomicin.