4506-66-5
4506-66-5 結(jié)構(gòu)式
基本信息
FAK自磷酸化抑制劑(Y15
1,2,4,5-四氨基苯鹽酸鹽
1,2,4,5-苯四胺四鹽酸鹽
苯-1,2,4,5-四胺四鹽酸鹽
1,2,4,5-苯四胺四鹽酸鹽 5G
1,2,4,5-TETRAAMINOBENZENE 四鹽酸鹽
1,2,4,5-苯四胺四鹽酸鹽,1,2,4,5-BENZENETETRAAMINE TETRAHYDROCHLORIDE
1,2,4,5-苯四胺 四鹽酸鹽,1,2,4,5-BENZENETETRAMINE TETRAHYDROCHLORIDE
1,2,4,5-苯四胺四鹽酸鹽,1,2,4,5-BENZENETETRAAMINE TETRAHYDROCHLORIDE,1,2,4,5-苯四胺 四鹽酸鹽,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
物理化學(xué)性質(zhì)
DMSO: 50mg/mL
安全數(shù)據(jù)
制備方法
4987-96-6
4506-66-5
1. 在惰性氣氛中處理4,6-二硝基-1,3-苯二胺，以防止氧化。向2加侖高壓釜中加入480g 1,5-二氨基-2,4-二硝基苯、5.5g錫粉（T1級(jí)）和9.6g Degussa F101 Pt/C催化劑。密封高壓釜后，用氮?dú)獯祾呦到y(tǒng)，并加入2000mL經(jīng)氮?dú)鈬娚涮幚淼囊掖肌?. 將高壓釜加熱至70℃，并用氫氣加壓至300psi。在80.5℃和300psi條件下保持反應(yīng)2小時(shí)。3. 反應(yīng)完成后，將高壓釜內(nèi)的混合物通過(guò)固體過(guò)濾器推入沉淀容器中。冷卻至15℃后，加入1400mL 12.1M HCl使1,2,4,5-苯四胺四鹽酸鹽沉淀。4. 收集沉淀的固體，依次用12.1M HCl和乙醇洗滌。在40℃下，通過(guò)氮?dú)夂驼婵赵谶^(guò)濾器上部分干燥產(chǎn)物。最終得到557.3g 1,2,4,5-苯四胺四鹽酸鹽，產(chǎn)率為81%。5. 為進(jìn)一步純化，可將1,2,4,5-苯四胺四鹽酸鹽通過(guò)濃鹽酸從水溶液中結(jié)晶。
參考文獻(xiàn)：
[1] Patent: US2014/66629, 2014, A1. Location in patent: Paragraph 0073-0075
[2] Journal of Organic Chemistry, 2015, vol. 80, # 10, p. 5210 - 5217
常見(jiàn)問(wèn)題列表
1,2,4,5-苯四胺四鹽酸鹽以劑量和時(shí)間依賴(lài)性方式直接阻斷粘著斑激酶（FAK）的磷酸化，并且還顯示出體內(nèi)乳腺腫瘤消退。已經(jīng)提出用FAK抑制劑14靶向FAK的Y397位點(diǎn)可以有效地用于癌癥治療。
| 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.