Uses
Braco-19 is a potenttelomerase/telomereinhibitor, preventing the capping and catalytic action of telomerase. Braco-19 acts as G-quadruplex (GQ) binding ligand, stabilizing G-quadruplexes formation at the 3V telomeric DNA overhang and produce rapid senescence or selective cell death. Braco-19 is also a HAdV virusreplication inhibitor[1][2].
Definition
ChEBI: N,N'-(9-{[4-(dimethylamino)phenyl]amino}acridine-3,6-diyl)bis(3-pyrrolidin-1-ylpropanamide) is a member of acridines and a N-alkylpyrrolidine.
in vivo
BRACO-19 (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[1]. BRACO-19 (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)[1].
| Animal Model: | Established UXF1138LX Xenografts in nude mice[1] |
| 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. |
References
[1] Angelika M Burger, et al. The G-quadruplex-interactive Molecule BRACO-19 Inhibits Tumor Growth, Consistent With Telomere Targeting and Interference With Telomerase Function. Cancer Res. 2005 Feb 15;65(4):1489-96. DOI:
10.1158/0008-5472.CAN-04-2910[2] Prativa Majee, et al. Genome-wide Analysis Reveals a Regulatory Role for G-quadruplexes During Adenovirus Multiplication. Virus Res. .2020 Jul DOI:
10.1016/j.virusres.2020.197960
