WJ460 is a potent myoferlin (MYOF) inhibitor, which interacts directly with MYOF[2]. WJ460 blocks breast cancer cell invasion with IC50 values of 43.37±3.42nM in MDA-MB-231[2]. However , WJ460 was inadequate in terms of metabolic stability and water solubility as well as binding activity with MYOF[3].
WJ460 (1μM, 24h) reduced Human T-cell leukemia virus type 1 (HTLV-1 infection) , which was correlated with a reduction in the intracellular level of mature Env[4]. WJ460 (50nM, 15h, 2Gy x-rays) treated HCT116 (cancer cell lines) spheroids were significantly radiosensitized as observed by a reduction in growth at day 15 post-seeding , compared with vehicle cells[5].
WJ460 (10mg/kg; 28 days; intraperitoneal injection) inhibits breast tumor growth, angiogenesis, and spontaneous metastasis in a mouse model[2]. WJ460(10mg/kg; 4weeks; intraperitoneal injection) caused a reduction of the abundance of ferroptosis core regulators solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX-4)[1].
WJ460 , a myoferlin inhibitor , exerts anti-metastatic activity in breast cancer[2].
References:
[1] RADEMAKER G, BOUMAHD Y, PEIFFER R, et al. Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells [J]. Redox Biol, 2022, 53(102324.
[2] ZHANG T, LI J, HE Y, et al. A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer [J]. Nat Commun, 2018, 9(1): 3726.
[3] GU H, ZHANG T, LI Y, et al. Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer [J]. Future Med Chem, 2022, 14(20): 1425-40.
[4] POLAKOWSKI N, SARKER M A K, HOANG K, et al. HBZ upregulates myoferlin expression to facilitate HTLV-1 infection [J]. PLoS Pathog, 2023, 19(2): e1011202.
[5] FOWLER H, CLIFFORD R E, BOWDEN D, et al. Myoferlin: A Potential Marker of Response to Radiation Therapy and Survival in Locally Advanced Rectal Cancer [J]. Int J Radiat Oncol Biol Phys, 2024, 120(4): 1111-23.
WJ460是一种有效的myoferlin（MYOF）抑制剂，可直接与MYOF相互作用[1]。WJ460阻断乳腺癌细胞侵袭，MDA-MB-231的IC50值为43.37±3.42nM[1]。然而，WJ460在代谢稳定性、水溶性以及与MYOF的结合活性方面存在不足[2]。
WJ460（1μM，24小时）下调了人类T细胞白血病病毒1型（HTLV-1）的感染，这与细胞内成熟Env水平的降低有关[3]。与对照组相比，用WJ460（50nM，15小时，2居里X射线）处理的HCT116（癌细胞系）球体在接种后第15天的生长明显减少，表明其对放射治疗的敏感性增加[4]。
WJ460 (10mg/kg；28天；腹腔注射) 抑制小鼠模型中乳腺肿瘤的生长、血管生成和自发转移[1]。WJ460（10mg/kg ; 4周；腹腔注射）导致铁死亡下调的核心调节因子溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX-4）丰度降低[5]。
WJ460，作为myoferlin抑制剂，在乳腺癌中有抗转移活性[1]。