CCI-38 Hydrochloride

CCI-38, a novel YTHDF2 inhibitor, exhibits high target affinity (KD: 10.1 µM) by competitively binding to its m6A/m5C pocket, specifically interacting with the unique C482 cysteine residue within YTHDF2; this interaction, coupled with its Michael acceptor moiety, drives its preferential selectivity over YTHDF1/3. CCI38 (IC50: 0.6-1.9 µM) destabilizes m5C-modified mRNA of ATP synthesis pathway genes, including ATP5PB/MF/MG, while upregulating m6A-modified mRNAs such as CD19/HLA-DMA/B, leading to reduced OXPHOS and reversed immune evasion. Furthermore, CCI-38 demonstrates in vivo efficacy in NSG mice xenografted with B-ALL, reducing tumor burden, prolonging survival, and sensitizing relapsed B-ALL to both CD19-CAR-T and blinatumomab with a dose of 0.25 mg/kg administered three times per week, making it a valuable candidate for enhancing T-cell immunotherapies.

Hygroscopic, store with desiccant