W1131

W1131 is a potent STAT3 inhibitor, triggering ferroptosis. W1131 suppresses cancer progression in gastric cancer cell subcutaneous xenograft model, organoids model, and PDX model. W1131 effectively alleviates chemical resistance of cancer cells to 5-FU (HY-90006). W1131 regulates cell cycle, DNA damage response, and oxidative phosphorylation, including IL6-JAK-STAT3 pathway and ferroptosis pathway[1].

Signaling Pathways >> Stem Cell/Wnt >> STAT

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

Signaling Pathways >> Apoptosis >> Ferroptosis

W1131（0-2 μM；72 h）抑制胃癌 AGS 细胞的存活、迁移和侵袭，并在处理 3 天后，抑制集落形成[1]。 W1131（0.1-3 μM；24 小时）有效抑制 AGS 细胞中 STAT3 的磷酸化[1]。 W1131（1 μM；48 小时）触发铁死亡并抑制胃癌中 GPX4、SLC7A11 和 FTH1 的表达[1]。 Western Blot Analysis[1] Cell Line: AGS cells Concentration: 0.1 μM, 0.3 μM, 1 μM, and 3 μM Incubation Time: 24 hours Result: Dose-dependently decreased the phosphorylated Y705-STAT3, but not STAT5, JAK2, and AKT. Immunofluorescence[1] Cell Line: AGS cells Concentration: 0.3 μM, 1 μM Incubation Time: 12 hours Result: Significantly promoted lipid ROS formation, and induced Fe2+ accumulation.

W1131（3 mg/kg，10 mg/kg；腹腔注射；每天一次，持续 2 周）以剂量依赖性方式抑制肿瘤生长，并在 BALB/c-nu/nu 小鼠的 MGC803 皮下异种移植模型中诱导铁死亡[1] 。 Animal Model: MGC803 subcutaneous xenografts in mouse[1] Dosage: 3 mg/kg, 10 mg/kg Administration: Intraperitoneal injection; once daily for 2 weeks Result: Inhibited GPX4, SLC7A11, and FTH1 expression level, indicating the induction of ferroptosis. Caused insignificant change of body weight.

[1]. Ouyang S, et al. Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer. Redox Biol. 2022 Jun;52:102317.