BRACO 19 trihydrochloride is a potent telomerase/telomere inhibitor with an IC50 value of 115±18nM, which prevents telomerase capping and catalysis[1]. BRACO 19 trihydrochloride is an acridine compound that acts as a quadruplex (GQ) binding ligand, stabilizing the formation of GQ quadruplexes at 3V telomeric DNA, leading to rapid senescence or selective cell death[2]. BRACO 19 trihydrochloride is a cancer cell proliferation inhibitor[3]. BRACO 19 trihydrochloride has anti-HIV-1 viral activity[4].
In vitro, BRACO 19 trihydrochloride (0-40μM) treatment of eGFP-transfected HEK293 cells for 12h dose-dependently reduced the intracellular AdV viral growth[5]. Treatment of human uterine cancer cell line UXF1138L cells with BRACO 19 trihydrochloride (1μM) for 24h significantly reduced the expression of telomerase reverse transcriptase (hTERT) in the nucleus[6].
In vivo, oral treatment of UXF1138L cell xenograft mice with BRACO 19 trihydrochloride (5mg/kg) for 3 weeks did not significantly inhibit tumor growth, but significantly decreased the level of hTERT in tumor cells[6].
References:
[1] Gowan S M, Harrison J R, Patterson L, et al. A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity[J]. Molecular pharmacology, 2002, 61(5): 1154-1162.
[2] Jayaprasad A G, Chandrasekharan A, Jyothi S P A, et al. Telomerase inhibitors induce mitochondrial oxidation and DNA damage-dependent cell death rescued by Bcl-2/Bcl-xL[J]. International Journal of Biological Macromolecules, 2024, 264: 130151.
[3] Schmidt A, Liu M. Recent advances in the chemistry of acridines[J]. Advances in heterocyclic chemistry, 2015, 115: 287-353.
[4] Perrone R, Butovskaya E, Daelemans D, et al. Anti-HIV-1 activity of the G-quadruplex ligand BRACO-19[J]. Journal of antimicrobial chemotherapy, 2014, 69(12): 3248-3258.
[5] Majee P, Shankar U, Pasadi S, et al. Genome-wide analysis reveals a regulatory role for G-quadruplexes during Adenovirus multiplication[J]. Virus research, 2020, 283: 197960.
[6] Burger A M, Dai F, Schultes C M, et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function[J]. Cancer research, 2005, 65(4): 1489-1496.
BRACO 19 trihydrochloride是一种有效的端粒酶/端粒抑制剂，IC50值为115±18nM，可防止端粒酶的加帽和催化作用[1]。BRACO 19 trihydrochloride是一种吖啶类化合物，可作为四联体（GQ）结合配体，稳定GQ四联体在3V端粒DNA处的形成，导致快速衰老或选择性细胞死亡[2]。BRACO 19 trihydrochloride是一种癌细胞增殖抑制剂[3]。BRACO 19 trihydrochloride具有抗HIV-1病毒活性[4]。
在体外，BRACO 19 trihydrochloride（0-40μM）处理eGFP转染的HEK293细胞12h，剂量依赖性地减少了细胞内AdV病毒的生长[5]。BRACO 19 trihydrochloride（1μM）处理人子宫癌细胞系UXF1138L细胞24h，显著降低了细胞核内端粒酶逆转录酶（hTERT）的表达[6]。
在体内，BRACO 19 trihydrochloride（5mg/kg）通过口服治疗UXF1138L细胞异种移植小鼠3周，对肿瘤生长抑制不显著，但肿瘤细胞中的hTERT水平显著下降[6]。