AB138

AB138 is a novel small molecule molecular glue degrader developed by Chengdu Fendi Pharmaceutical for the treatment of acute myeloid leukemia (AML). It acts by facilitating a ternary complex between the G1-to-S phase transition protein 1 (GSPT1) and the cereblon (CRBN) E3 ubiquitin ligase, leading to the rapid and sustained proteasomal degradation of GSPT1. This degradation activates the integrated stress response, evidenced by eIF2α phosphorylation and upregulation of ATF3 and CHOP, which subsequently downregulates oncogenic drivers such as c-Myc and the anti-apoptotic protein MCL1. Preclinical studies demonstrate that oral administration of AB138 induces S-phase arrest and apoptosis in AML cell lines and significantly reduces tumor burden in xenograft models without significant toxicity.