Pyridostatin

Short Summary : Drug used for promoting growth arrest

Category : Cell Cycle/Checkpoint|G-quadruplex

Purity : 0.98

CAS Number : 1085412-37-8

Formula : C31H32N8O5

Molecular Weight : 596.64

SMILE : C1=CC=C2C(=C1)C(=CC(=N2)NC(=O)C3=CC(=CC(=N3)C(=O)NC4=NC5=CC=CC=C5C(=C4)OCCN)OCCN)OCCN

Solubility : >20.85mg/mL in DMSO

Storage : Store at -20°C

Description : Pyridostatin is a synthetic small-molecule stabilizer of G-quadruplexe [1].G-quadruplexe is a kind of secondary structure of DNA that usually exists in the end of the chromosome or the telomeres. Since G-quadruplexe is also enriched in the promoters of a serious of proto-oncogenes including c-kit, K-ras and Bcl-2, they are thought to participate in the regulation of gene replication and transcription. Besides that, G-quadruplexe has been found to affect the elongation, replication and capping of telomeres. Based on these findings, a lot of small molecules that can interact with G-quadruplexe have been designed and synthesized to help demonstrate the existence and roles of G-quadruplexe or to be developed as selective anti-cancer drugs. It has been reported that some small molecules interacting with G-quadruplexe can cause the progressive shortening of telomeres and subsequently the active the DNA damage response resulting in cell cycle arrest. Among these molecules, pyridostatin is a synthetic small-molecule stabilizer of G-quadruplexe with the ability to adapt the dynamic and diverse structures of G-quadruplex. Pyridostatin competed for binding with the telomere associated proteins and induced the dysfunction of telomeres [1 and 2]. In the FRET melting assay using human telomeric G-quadruplex-forming sequence and ds-DNA, pyridostatin showed maximal stabilization effect of the G-quadruplex sequence at concentration of 1 ?M while showed no effect on the ds-DNA. In a panel of three cancer cell lines (HeLa, U2OS and HT1080) and a normal cell line (WI-38), treatment of pyridostatin significantly inhibited cell growth with IC50 values of 0.89 to 10 ?M after 72 hours. The selectivity of pyridostatin against HT1080 cells was 18-fold higher than that against the normal cells [1 and 3]. References:[1] Mela I, Kranaster R, Henderson R M, et al. Demonstration of ligand decoration, and ligand-induced perturbation, of G-quadruplexes in a plasmid using atomic force microscopy. Biochemistry, 2012, 51(2): 578-585.[2] Müller S, Sanders D A, Di Antonio M, et al. Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells. Organic & biomolecular chemistry, 2012, 10(32): 6537-6546.[3] McLuckie K I E, Di Antonio M, Zecchini H, et al. G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells. Journal of the American Chemical Society, 2013, 135(26): 9640-9643.

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