CHMFL-BMX-078 is a highly potent and selective type II irreversible BMX kinase inhibitor with an IC50 of 11 nM.

BMX kinase:11 nM.

CHMFL-BMX-078在KINOMEscan评估中对468种激酶/突变体显示出高度选择性，对BTK激酶的选择性至少为40倍（IC50=437 nM）。对于BMX激酶的非活化状态，CHMFL-BMX-078显示出81 nM的结合Kd，而对于BMX激酶的活化状态，其展示出10200 nM的结合Kd。CHMFL-BMX-078对BaF3-TEL-BMX细胞展示出抗增殖效应（GI50=0.016 μM），并且相较于亲本BaF3细胞具有选择性。对于BMX总酪氨酸磷酸化的抑制，CHMFL-BMX-078对BMX wt（EC50=5.8 nM）的功效大约是对C496S突变体（EC50=459 nM）的80倍。

CHMFL-BMX-078 在静脉注射时显示出可接受的最大浓度(Cmax)（13565.23 ng/mL）和从给药至最后一次测定浓度时间点的化合物暴露量(AUC0-t)（1386.41 ng/mL h）。然而，此化合物通过口服给药不被吸收，表明作为研究工具时，应通过静脉(i.v.)或腹腔(i.p.)注射的方式给药。

The kinase reaction system contains BMX or BTK, 1 μL of serially diluted CHMFL-BMX-078, and substrate Poly peptidewith 100 μM ATP. The reaction in each tube is started immediately by adding ATP and kept going for an hour under 37 °C. After the tube cooled for 5 min at room temperature, 5 μL solvent reactions are carried out in a 384-well plate. Then 5 μL of ADP-Glo reagent is added into each well to stop the reaction and consume the remaining ATP within 40 min. At the end, 10 μL of kinase detection reagent is added into the well and incubated for 30 min to produce a luminescence signal. Luminescence signal is measured with an automated plate reader.

CHMFL-BMX-078 is dissolved in 55% saline containing 5% DMSO and 40% PEG400 by vortex. The final concentration of the stock solution is 1 mg/mL for administration.Rat: Six 8-week-old male Sprague?Dawley rats are fasted overnight before starting drug treatment via intravenous and oral administration. Animal blood collection time points are as follows. For groups 1, 3, and 5 (intravenous): 1 min, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, and 8 h before and after administration is selected. For group 2, 4, and 6 (oral): 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h before and after dosing. The plasma is collected for analysis.