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XMD8-92

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Chemical Structure| 1234480-50-2 同义名 : -
CAS号 : 1234480-50-2
货号 : A146338
分子式 : C26H30N6O3
纯度 : 99%+
分子量 : 474.555
MDL号 : MFCD18782742
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(105.36 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • BET

    BRD4 (1), Kd:170 nM
描述 BMK1 (Big MAP Kinase 1) is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. BMK1 is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors[3]. XMD8-92 is a BMK1 inhibitor. The dissociation constant (Kd) of XMD8-92 towards BMK1 was 80 nM, and data of XMD8-92 against other kinases suggested selectivity of XMD8-92 to BMK1. In a kinase activity assay utilizing Hela cell lysates, the IC50 of XMD8-92 against BMK1 was 1.5 μM. Furthermore, growth factor-induced activation of cellular BMK1 was effectively blocked by 1 μM XMD8-92, detected by mobility retardation. Cell proliferation assay revealed that 5 μM XMD8-92 inhibited more than 50% PC3, Hela and LL/2 cell growth when incubated for 48h[4]. 48h treatment of 25 μM XMD8-92 also inhibited cell proliferation of pancreatic tumor AsPC-1cells to the extent of more than 50%[5]. In animal experiments, treatment of mice bearing Hela or LL/2 xenografts with XMD8-92 at the dose of 50 mg/kg twice daily 1 day, several days, or weeks after inoculation of the tumor cells all significantly inhibit the growth of the tumors[4]. In an AsPC-1 xenograft model established in NOD/SCID mice, XMD8-92 administrated at the dose of 50 mg/kg i.p. daily for 15 days significantly inhibited tumor growth[5].
作用机制 XMD8-92 inhibits BMK1 via ATP site competition-binding. The selective binding and inhibition of XMD8-92 towards BMK1 was revealed by ATP-site competition binding assay and KiNativ method utilizing Hela cell lysates[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human HeLa cells Function assay Inhibition of EGF-induced BMK1 autophosphorylation in human HeLa cells by SDS-PAGE analysis, IC50=0.24 μM 21412406
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.54mL

2.11mL

1.05mL

21.07mL

4.21mL

2.11mL
参考文献

[1]Sureban SM, May R, et al. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014 Aug 28;351(1):151-61.

[2]Yang Q, Deng X, et al. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14;18(3):258-67.

[3]Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 1998 Oct 15;395(6703):713-6.

[4]Yang Q, Deng X, Lu B, Cameron M, Fearns C, Patricelli MP, Yates JR 3rd, Gray NS, Lee JD. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14;18(3):258-67.

[5]Sureban SM, May R, Weygant N, Qu D, Chandrakesan P, Bannerman-Menson E, Ali N, Pantazis P, Westphalen CB, Wang TC, Houchen CW. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014 Aug 28;351(1):151-61.