SJ42872

SJ42872 is a potent and selective molecular glue degrader of peptidylprolyl isomerase-like 4 (PPIL4), a cyclophilin family protein and component of the spliceosome. Developed by St. Jude Children's Research Hospital, it functions by facilitating a ternary complex between PPIL4 and the Cereblon (CRBN) E3 ubiquitin ligase, leading to the rapid proteasomal degradation of PPIL4 (DC50 10-100 nM). SJ42872 exhibits high selectivity, sparing other common CRBN neosubstrates such as GSPT1, CK1α, and IKZF1/3. Preclinical studies in acute leukemia (AL) and medulloblastoma (MB) cell lines and patient-derived xenograft (PDX) models have shown that PPIL4 degradation induces cell cycle arrest and apoptosis, significantly reducing tumor growth and leukemia burden. The compound's activity in CRLF2-rearranged and DUX4-rearranged leukemia, as well as its ability to cross the blood-brain barrier in medulloblastoma models, highlights its potential as a novel therapeutic for pediatric cancers.