ZXH-4-130 is a potent and selective CRBN degrader, functioning as a hetero-PROTAC compound with the inclusion of CRBN-VHL.

ZXH-4-130 (100 nM; 2 h pre-treatments; followed by 96-hour treatment with 1 μM of Pomalidomide) prevents Pomalidomide (1 μM) cytotoxicity to a significant extent, ZXH-4-130 has statistically significant amounts of prevention[1]. MM1.S cells are pre-treated for 2 h with 50 nM of ZXH-4-130, before exposing them to CC-885, a compound that induces G1 to S phase transition protein 1 (GSPT1) degradation via CRBN E3 ligase recruitment. Pretreatment with 50 nM of ZXH-4-130 rescued GSPT1 degradation[1]. ZXH-4-130 (100 nM 2 h pre-treatment; followed by 6 h treatment with THAL-SNS-032) induces nearly complete CRBN degradation, but THAL-SNS-032's activity against CDK9 is only partially prevented[1]. Cell Viability Assay[1]Cell Line: MM1.S cells Concentration: 100 nM Incubation Time: 2 h pre-treatments; followed by 96-hour treatment with 1 μM of Pomalidomide Result: Prevented Pomalidomide cytotoxicity to a significant extent, ZXH-4-130 has statistically significant amounts of prevention. Western Blot Analysis[1]Cell Line: MM1.S cells Concentration: 50 nM Incubation Time: 2 h pretreatment with ZXH-4-130, followed by 4 h treatment with CC-885 Result: Rescued GSPT1 degradation.