WX2-43

WX2-43 is a PRMT5-KLF4 inhibitor ( K d of 11.0 nM). WX2-43 binds to the region between amino acids L400-M500 on PRMT5. WX2-43 efficiently intercepts the interaction between KLF4 and PRMT5, and blocks KLF4 methylation. WX2-43 decreases p21 levels and increases Bax levels. WX2-43 suppresses triple negative breast tumor progression. WX2-43 can be used in the research of triple-negative breast cancer and colorectal cancer ^{[1] [2]}.

In Vivo, WX2-43 (40-80 mg/kg; i.p.; twice weekly; 4 weeks) suppresses triple negative breast tumor progression in nude mice^[1].

In Vitro, WX2-43 (biotin-WX2-43; 0.1 nM-10 μM; 2 h) binds to PRMT5 with a Kd of 11.0 nM^[1]. WX2-43 (0.03-10 μM; 24 h) inhibits cell viability in a KLF4-dependent manner in MEFs treated with cisplatin^[1]. WX2-43 is more potent in TNBC cell lines (EC50 0.44-0.96 μM) than in normal mammary epithelial cell lines (EC50 3.62-23.34 μM)^[1]. WX2-43 can induce a mesenchymal-like phenotype in two-dimensional (2D) AKPS cultures, altering colony morphology, size, and actin cytoskeleton, and reducing the frequency of Ki-67+ cells^[2].

References:
[1]. Zhou Z, et al. A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy. EBioMedicine. 2019;44:98-111.
[2]. Borrelli C, et al. In vivo interaction screening reveals liver-derived constraints to metastasis. Nature. 2024;632(8024):411-418.