YD23 is a SMARCA2 PROTAC. YD23 induces degradation of SMARCA2, which is synthetic lethal to SMARCA4. Moreover, YD23 decreases chromatin accessibility at enhancers of a number of genes including cell cycle and cell growth regulatory genes. YD23 reduces chromatin accessibility only in SMARCA4 deficient cells mechanistically.
References:
[1]. Kotagiri S, et al. Novel SMARCA2 degrading bifunctional molecules as therapeutics in SMARCA4 mutant lung cancer[J]. Cancer Research, 2023, 83(7_Supplement): 1138-1138.
[2]. Kotagiri S, et al. Enhancer reprogramming by novel SMARCA2 degrading PROTACs underlies therapeutic utility in SMARCA4 mutant tumors[J]. Cancer Research, 2023, 83(7_Supplement): 6289-6289.