XMD8-92 is a BMK1 kinase inhibitor, with an IC50 of 1.5μM and a dissociation constant (Kd) of 80nM[1].
In vitro, XMD8-92 (0, 0.78, 1.56, 3.13, 6.25, 12.50 and 25µM; 48h) inhibits the proliferation of AsPC-1 cancer cells in a dose-dependent manner[2]. XMD8-92 (10µM; 1h) treatment prevents epidermal growth factor (EGF) or hypoxia-induced migration of hepatocellular carcinoma (HCC) cells and induces cytoskeletal remodeling[3].
In vivo, XMD8-92 (50mg/kg/twice a day; 28 days; i.p.) significantly inhibited the growth of tumors in xenografted mice[1]. XMD8-92 (50mk/kg; 15 days; i.p.) inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism[2]. Treatment with XMD8-92 (10mg/kg; once per week; s.c.) significantly reduced retinal inflammation, VEGF production, and oxidative stress in diabetic mice[4].
References:
[1] Yang Q, Deng X, Lu B, et al. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14;18(3):258-67.
[2] Sureban SM, May R, Weygant N, et al. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014 Aug 28;351(1):151-61.
[3] Rovida E, Di Maira G, Tusa I, et al. The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma. Gut. 2015 Sep;64(9):1454-65.
[4] Howell SJ, Lee CA, Batoki JC, et al. Retinal Inflammation, Oxidative Stress, and Vascular Impairment Is Ablated in Diabetic Mice Receiving XMD8-92 Treatment. Front Pharmacol. 2021 Aug 11;12:732630.
XMD8-92是一种BMK1激酶抑制剂，IC50为1.5µM，解离常数（Kd）为80nM[1]。
在体外实验中，在体外，XMD8-92（0, 0.78, 1.56, 3.13, 6.25, 12.50和25µM; 48h）能以剂量依赖性方式抑制AsPC-1癌细胞的增殖[2]。XMD8-92（10µM; 1h）处理可阻止表皮生长因子（EGF）或缺氧诱导的肝细胞癌（HCC）细胞迁移，并诱导细胞骨架重塑[3] 。
在体内实验中，XMD8-92（50mg/kg/一天两次; 28天; i.p.）显著抑制了异种移植小鼠中肿瘤的生长[1]。XMD8-92（50mg/kg; 15天; i.p.）通过DCLK1依赖性机制抑制胰腺肿瘤异种移植生长[2]。XMD8-92（10mg/kg; 每周一次; s.c.）处理显著减轻了糖尿病小鼠的视网膜炎症、VEGF产生和氧化应激[4]。