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Pyridostatin

Catalog No.
A3742
Drug used for promoting growth arrest
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$130.00
In stock
5mg
$70.00
In stock
10mg
$105.00
In stock
25mg
$210.00
In stock
50mg
$350.00
In stock

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Background

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 μM 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 μM 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.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt596.64
Cas No.1085412-37-8
FormulaC31H32N8O5
SynonymsRR-82;RR82;RR 82
Solubility≥20.85 mg/mL in DMSO, ≥30.87 mg/mL in EtOH with gentle warming, ≥9.66 mg/mL in H2O with ultrasonic and warming
Chemical Name4-(2-aminoethoxy)-2-N,6-N-bis[4-(2-aminoethoxy)quinolin-2-yl]pyridine-2,6-dicarboxamide
SDFDownload SDF
Canonical SMILESC1=CC=C2C(=C1)C(=CC(=N2)NC(=O)C3=CC(=CC(=N3)C(=O)NC4=NC5=CC=CC=C5C(=C4)OCCN)OCCN)OCCN
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

HeLa, HT1080, U2OS and WI-38 cell lines

Preparation method

The solubility of this compound in DMSO is >20.85 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0–40 μM for 72 h

Applications

A previous study investigated the growth inhibition after 3 days of exposure to pyridostatin on a panel of four human cell lines: HeLa (adenocarcinoma), HT1080 (fibrosarcoma), U2OS (osteosarcoma), and WI-38 (normal lung fibroblasts), the latter being non-cancerous. Pyridostatin showed growth inhibition at high nanomolar to low micromolar concentrations against these tested cell lines. In addition, pyridostatin exhibited an 18.5-fold selectivity for HT1080 cells over WI-38 cells.

References:

[1] 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.

Quality Control

Chemical structure

Pyridostatin

Related Biological Data

Pyridostatin

Related Biological Data

Pyridostatin