4506-66-5
4506-66-5 结构式
基本信息
FAK自磷酸化抑制剂(Y15
1,2,4,5-四氨基苯盐酸盐
1,2,4,5-苯四胺四盐酸盐
苯-1,2,4,5-四胺四盐酸盐
1,2,4,5-苯四胺四盐酸盐 5G
1,2,4,5-TETRAAMINOBENZENE 四盐酸盐
1,2,4,5-苯四胺四盐酸盐,1,2,4,5-BENZENETETRAAMINE TETRAHYDROCHLORIDE
1,2,4,5-苯四胺 四盐酸盐,1,2,4,5-BENZENETETRAMINE TETRAHYDROCHLORIDE
1,2,4,5-苯四胺四盐酸盐,1,2,4,5-BENZENETETRAAMINE TETRAHYDROCHLORIDE,1,2,4,5-苯四胺 四盐酸盐,1,2,4,5-BENZENETETRAMINE TETRAHYDROCHLORIDE
Y-15
NSC 667249
FAK Inhibitor 14
FAK inhibitor Y15
Benzene-1,2,4,5-tetrayL
tetraamine tetrahydrochL
Benzene-1,2,4,5-tetraMine 4HCl
1,2,4,5-Benzenetetraamine 4HCl
1,2,4,5-BenzenetetraminetetraHCl
物理化学性质
DMSO: 50mg/mL
制备方法
4987-96-6
4506-66-5
1. 在惰性气氛中处理4,6-二硝基-1,3-苯二胺，以防止氧化。向2加仑高压釜中加入480g 1,5-二氨基-2,4-二硝基苯、5.5g锡粉（T1级）和9.6g Degussa F101 Pt/C催化剂。密封高压釜后，用氮气吹扫系统，并加入2000mL经氮气喷射处理的乙醇。2. 将高压釜加热至70℃，并用氢气加压至300psi。在80.5℃和300psi条件下保持反应2小时。3. 反应完成后，将高压釜内的混合物通过固体过滤器推入沉淀容器中。冷却至15℃后，加入1400mL 12.1M HCl使1,2,4,5-苯四胺四盐酸盐沉淀。4. 收集沉淀的固体，依次用12.1M HCl和乙醇洗涤。在40℃下，通过氮气和真空在过滤器上部分干燥产物。最终得到557.3g 1,2,4,5-苯四胺四盐酸盐，产率为81%。5. 为进一步纯化，可将1,2,4,5-苯四胺四盐酸盐通过浓盐酸从水溶液中结晶。
参考文献：
[1] Patent: US2014/66629, 2014, A1. Location in patent: Paragraph 0073-0075
[2] Journal of Organic Chemistry, 2015, vol. 80, # 10, p. 5210 - 5217
常见问题列表
1,2,4,5-苯四胺四盐酸盐以剂量和时间依赖性方式直接阻断粘着斑激酶（FAK）的磷酸化，并且还显示出体内乳腺肿瘤消退。已经提出用FAK抑制剂14靶向FAK的Y397位点可以有效地用于癌症治疗。
| Target | Value |
|
FAK
(Cell-free assay) |
Y15 directly blocks autophosphorylation activity of FAK. Y15 inhibits Y397 phosphorylation of FAK starting at 0.1 μM in Panc-1 cells. At a dose of 100 μM, Y15 has the same or better inhibition as TAE226. Of note, total FAK is downregulated at higher doses of Y15. Y15 also blocks phosphorylation of the FAK downstream substrate, paxillin. Total paxillin is decreased at higher doses similar to FAK. Thus, Y15 inhibits FAK phosphorylation in a dose-dependent manner. MTS assay is completed using a range of Y15 doses on all cell lines (TT, K1, BCPAP, and TPC1, respectively).Y15 inhibited cell viability in a dose-dependent manner across all thyroid cell lines evaluated. IC 50 is 2.05, 5.74, 9.99, and 17.54 μM for TT, TPC1, BCPAP, and K1, respectively.
Nude mice bearing Panc si-ctrl xenografts are treated with TAE226, a dual FAK and IGF-1R tyrosine kinase inhibitor, to provide a reference for the antitumor effect of dual inhibition of FAK and IGF-1R. Without drug treatment, Panc si5-IGF-1R xenografts grew slower than Panc si-ctrl xenografts (Panc si5-IGF-1R/PBS vs. Panc si-ctrl/PBS), suggesting moderate tumor suppression by inhibiting the IGF-1R pathway only. Further inhibition of FAK activity by Y15 treatment suppresses the growth of Panc si5-IGF-1R xenografts more drastically (Panc si5-IGF-1R/PBS vs. Panc si5-IGF-1R/Y15). A similar antitumor effect is seen in Panc si-ctrl xenografts treated with TAE226 (Panc si5-IGF-1R/Y15 vs. Panc si-ctrl/TAE226). Mice demonstrates normal grooming and eating habits throughout the experiment.