Pyridostatin TFA salt

Pyridostatin stabilizes G-quadruplexes (G4s) in cells and elicits a DNA damage response by causing the formation of DNA double strand breaks (DSB). Pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. Pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC.

Product information

CAS Number: 1085412-37-8

Molecular Weight: 938.71

Formula: C37H35F9N8O11

Synonym:

Pyridostatin

PDS

Pyridostatin TFA salt

Related CAS Number:

1472611-44-1 (TFA)

Chemical Name: 4-(2-aminoethoxy)-N2,N6-bis(4-(2-aminoethoxy)quinolin-2-yl)pyridine-2,6-dicarboxamide tris(2,2,2-trifluoroacetate)

Smiles: NCCOC1C=C(N=C(C=1)C(=O)NC1=CC(OCCN)=C2C=CC=CC2=N1)C(=O)NC1=CC(OCCN)=C2C=CC=CC2=N1.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F

InChiKey: CYYZQGUDHAKBIQ-UHFFFAOYSA-N

InChi: InChI=1S/C31H32N8O5.3C2HF3O2/c32-9-12-42-19-15-24(30(40)38-28-17-26(43-13-10-33)20-5-1-3-7-22(20)36-28)35-25(16-19)31(41)39-29-18-27(44-14-11-34)21-6-2-4-8-23(21)37-29;3*3-2(4,5)1(6)7/h1-8,15-18H,9-14,32-34H2,(H,36,38,40)(H,37,39,41);3*(H,6,7)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Pyridostatin (RR82) hydrochloride (10 μM; 48 hours) induces cell cycle arrest. Pyridostatin TFA is a very selective G-quadruplex DNA-binding small molecule designed to form a complex with and stabilize G-quadruplex structure. Pyridostatin TFA causes neurite retraction, synaptic loss, and dose-dependent neuronal death. In cultured primary neurons, Pyridostatin TFA induces the formation of DNA DSBs. Remarkably, Pyridostatin TFA (1-5 μM, overnight) downregulates the BRCA1 protein, a protein that guards and repairs the neuronal genome, at the transcriptional level.

References:

1. Marchand A, Granzhan A, Iida K, Tsushima Y, Ma Y, Nagasawa K, Teulade-Fichou M, Gabelica V. Ligand-Induced Conformational Changes with Cation Ejection upon Binding to Human Telomeric DNA G-Quadruplexes. J Am Chem Soc. 2015 Jan 6. [Epub ahead of print] PubMed PMID: 25525863.
2. Murat P, Zhong J, Lekieffre L, Cowieson NP, Clancy JL, Preiss T, Balasubramanian S, Khanna R, Tellam J. G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation. Nat Chem Biol. 2014 May;10(5):358-64. doi: 10.1038/nchembio.1479. Epub 2014 Mar 16. PubMed PMID: 24633353; PubMed Central PMCID: PMC4188979.
3. Murat P, Gormally MV, Sanders D, Di Antonio M, Balasubramanian S. Light-mediated in cell downregulation of G-quadruplex-containing genes using a photo-caged ligand. Chem Commun (Camb). 2013 Oct 4;49(76):8453-5. doi: 10.1039/c3cc44737e. PubMed PMID: 23949446; PubMed Central PMCID: PMC4155816.
4. Husby J, Todd AK, Platts JA, Neidle S. Small-molecule G-quadruplex interactions: Systematic exploration of conformational space using multiple molecular dynamics. Biopolymers. 2013 Dec;99(12):989-1005. doi: 10.1002/bip.22340. PubMed PMID: 23828641.
5. McLuckie KI, Di Antonio M, Zecchini H, Xian J, Caldas C, Krippendorff BF, Tannahill D, Lowe C, Balasubramanian S. G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells. J Am Chem Soc. 2013 Jul 3;135(26):9640-3. doi: 10.1021/ja404868t. Epub 2013 Jun 25. PubMed PMID: 23782415; PubMed Central PMCID: PMC3964824.

Products are for research use only. Not for human use.