N，N′-[9[[4-(二甲基氨基)苯基]氨基]-3,6-ac啶二基]双-1-吡咯烷丙酰胺三盐酸盐 | 1177798-88-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N，N′-[9[[4-(二甲基氨基)苯基]氨基]-3,6-ac啶二基]双-1-吡咯烷丙酰胺三盐酸盐
• 英文名称: BRACO 19 trihydrochloride
• 英文别名: N-[9-[4-(dimethylamino)anilino]-6-(3-pyrrolidin-1-ylpropanoylamino)acridin-3-yl]-3-pyrrolidin-1-ylpropanamide;trihydrochloride
• CAS: 1177798-88-7
• 化学式: C35H46Cl3N7O2
• 分子量: 703.1
• InChiKey: MJAPNWJRLLDPAB-UHFFFAOYSA-N

物化性质

• 溶解度：
  H2O：可溶5mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  7.31
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  92.8
• 氢给体数：
  6
• 氢受体数：
  7

制备方法与用途

生物活性

Braco-19 trihydrochloride 是一种有效的端粒酶/端粒 (telomerase/telomere) 抑制剂，可防止端粒酶的催化作用。Braco-19 trihydrochloride 作为四联体 (GQ) 结合配体，稳定 GQ 四联体在 3V 端粒 DNA 处的形成，并可以导致快速衰老或选择性细胞死亡。Braco-19 trihydrochloride 也是一种HAdV病毒复制抑制剂。

靶点

IC50: telomerase

体外研究

Braco-19 trihydrochloride, as a well-known GQ binding ligand, interacts specifically with the HAdV GQs and increases their stability, and blocks the HAdV multiplication.BRACO-19 trihydrochloride (1.0-10 μM; 5 day) cause zero growth inhibition is found 1 μM, the IC ₅₀ for BRACO-19 in UXF1138L cells is 2.5 μM, the IC ₁₀₀ is 5 μM.BRACO-19 trihydrochloride (1 μM; 24 hours) shows dramatically reduced nuclear hTERT expression. However, residual cytoplasmic hTERT staining is observed accompanied by the occurrence of atypical mitoses.BRACO-19 trihydrochloride (0-40 μM; 24 hours) decreases the AdV virus growth in a dose-dependent manner in eGFP-transinfected HEK 293 cells.BRACO-19 trihydrochloride (0-150 μM; 24 hours) shows a decrease in band intensity in an increasing concentration-dependent manner.

Cell Viability Assay

Cell Line:	HEK 293 cells
Concentration:	20 μM; 40 μM
Incubation Time:	24 hours
Result:	Displayed low cytotoxicity and decreased the eGFP fluorescence.

体内研究

BRACO-19 trihydrochloride (oral administration or intraperitoneal injection; 2 or 5 mg/kg; 3 weeks) oral dosing regimen are always inactive and the animals have to be sacrificed due to high tumor burden before overall termination of the study, Chronic, i.p. BRACO-19 administration, qdx5 is efficient in inhibiting tumor growth in earlystage xenografts but not advanced-stage xenografts. BRACO-19 trihydrochloride (intraperitoneal injection; 2 mg/kg; 3 weeks; starting 6 days after transplantation of UXF1138LX fragments) inhibits tumor growth significantly and under these conditions, marked single-agent antitumor activity is observed, with some animals in the group showing complete regressions (5 of 12 tumors).

Animal Model:	Established UXF1138LX Xenografts in nude mice
Dosage:	2 mg/kg
Administration:	Intraperitoneal injection; 3 weeks; starting 6 days after transplantation of UXF1138LX fragments
Result:	Showed partial tumor regressions with an optimal T/C on day 28 of 4.1%, equal to 95.9% inhibition of tumor growth compared with control.