XMD8-92 is an effective and specific BMK1/ERK5 inhibitor (Kd: 80 nM).

BMK1:80 nM(Kd)

通过对DCLK1及其几个下游靶点的显著下调,XMD8-92可抑制胰腺肿瘤异种移植物的生长.XMD8-92（50 mg/kg,i.p.）可阻断肿瘤细胞增殖以及肿瘤相关的血管生成,从而使异种移植人或同源小鼠肿瘤的生长被显著抑制.

羟基红花黄色素A对肝星状细胞的活化具有抑制作用,XMD8-92可显著阻断该作用,并抑制HSYA介导的MEF2C下调。通过抑制BMK1活化,XMD8-92可显著诱导细胞中p21表达,并抑制癌细胞的增殖。

KiNativ profiling of XMD8-92 is carried out with both an ATP and ADP acylphosphate-desthiobiotin with the following modifications. HeLa cell lysates (5 mg/mL total protein) are incubated in the presence of XMD8-92 at 50 μM, 10 μM, 2 μM, 0.8 μM, and 0 μM for 15 minutes prior to addition of the ATP or ADP acylphosphate probe (5 μM final probe concentration). All reactions are performed in duplicate. Probe reactions proceeded for 10 minutes and the reaction stopped by the addition of urea and processed for MS analysis. Samples are analyzed by LC-MS/MS on a linear ion trap mass spectrometer using a time segmented "target list" designed to collect MS/MS spectra from all kinase peptide-probe conjugates that can be detected in HeLa cell lysates. This target list is generated and validated by prior exhaustive analysis of HeLa lysates. Up to four characteristic fragment ions for each kinase peptide-probe conjugate are used to extract signals for each kinase, and a comparison of inhibitor treated to control (untreated) lysates allow for precise determination of % inhibition at each point. A manuscript describing the details of this targeted mass spectrometry approach is in preparation[1].