ZXH-4-130 TFA is an efficient and selective CRBN degrader, which can regulate substrate recognition characteristics [1]. ZXH-4-130 TFA restores the levels of GSPT1 proteins and prevent CDK9 degradation by degrading the CRBN protein [2]. ZXH-4-130 TFA is widely used as an alternative chemical probe for CRBN knockdown and as a model compound for site modification to develop novel molecules with high efficiency for targeting CRBN[3].
In vitro, ZXH-4-130 TFA treatment (100nM) for 2 hours significantly inhibited the cytotoxicity of pomalidomide against MM1.S cells and restored cell viability[4].
References:
[1] Fan G, Chen S, Zhang Q, et al. Proteolysis‐Targeting Chimera (PROTAC): Current Applications and Future Directions[J]. MedComm, 2025, 6(10): e70401.
[2] Diehl C J, Ciulli A. Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders[J]. Chemical Society Reviews, 2022, 51(19): 8216-8257.
[3] Pichlak M, Sobierajski T, Błażewska K M, et al. Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues[J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2023, 38(1): 2254012.
[4] Powell C E, Du G, Bushman J W, et al. Selective degradation-inducing probes for studying cereblon (CRBN) biology[J]. RSC Medicinal Chemistry, 2021, 12(8): 1381-1390.
ZXH-4-130 TFA是一种高效、选择性的CRBN降解剂，能够调节底物识别特性[1]。ZXH-4-130 TFA通过降解CRBN蛋白，恢复GSPT1蛋白水平并阻止CDK9降解[2]。ZXH-4-130 TFA被广泛用作CRBN敲低的替代化学探针，并作为位点修饰的模型化合物，以开发高效靶向CRBN的新型分子[3]。
在体外，100nM的ZXH-4-130 TFA处理MM1.S细胞2小时，显著抑制了pomalidomide对MM1.S细胞的细胞毒性，并恢复了细胞活力[4]。