WX2-43

WX2-43 is a PRMT5-KLF4 inhibitor. Biotin-labeled WX2-43 binds to GST-PRMT5 with a dissociation constant Kd of 11.0 nM. It binds to the L400 to M500 amino acid region of PRMT5 protein, effectively blocking the interaction between KLF4 and PRMT5 and inhibiting KLF4 methylation modification. Functionally, WX2-43 downregulates p21 expression and upregulates Bax level, thereby suppressing the progression of triple-negative breast tumors. It can be applied to mechanism research of triple-negative breast cancer and colorectal cancer.

PRMT5-KLF4:11.0 nM (Kd)

Methods: Biotinylated WX2-43 was used for target binding assay to determine its binding affinity with PRMT5. Cell viability detection, cell phenotypic analysis and immunofluorescence staining were performed to evaluate its activity and selectivity in different cell models, as well as its effects on cell morphology and proliferation.
Results: :
1.Target binding affinity: Biotinylated WX2-43 (0.1 nM–10 μM, incubation for 2 h) could specifically bind to PRMT5 with a dissociation constant (Kd) of 11.0 nM.
2.Cell viability inhibition: WX2-43 (0.03–10 μM, treatment for 24 h) inhibited cell viability in cisplatin-treated MEFs in a KLF4-dependent manner.
3.Cell selectivity: WX2-43 exhibited stronger activity in triple-negative breast cancer (TNBC) cell lines with EC₅₀ values of 0.44–0.96 μM, which was significantly higher than that in normal mammary epithelial cell lines (EC₅₀: 3.62–23.34 μM) [1].
4.Effects on cell phenotype and proliferation: WX2-43 could induce a mesenchymal-like cell phenotype in a two-dimensional (2D) AKPS culture system, alter colony morphology and size, remodel the actin cytoskeleton, and reduce the frequency of Ki-67+ proliferative cells [2].

Methods: Nude mice bearing triple-negative breast cancer tumors were given intraperitoneal injection to observe the inhibitory effect of WX2-43 on tumor growth in vivo.
Results: WX2-43 (40–80 mg/kg, intraperitoneal injection, twice a week for 4 consecutive weeks) could significantly inhibit the tumor progression of triple-negative breast cancer in nude mice [1].