WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406602
CAS#: 1472611-44-1 (TFA)
Description: 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.
MedKoo Cat#: 406602
Name: Pyridostatin TFA salt
CAS#: 1472611-44-1 (TFA)
Chemical Formula: C37H35F9N8O11
Exact Mass:
Molecular Weight: 938.72
Elemental Analysis: C, 47.34; H, 3.76; F, 18.21; N, 11.94; O, 18.75
Related CAS #: 1472611-44-1 (TFA) 1085412-37-8 (free base) 1629261-49-9 (HCl)
Synonym: Pyridostatin; PDS; Pyridostatin TFA salt
IUPAC/Chemical Name: 4-(2-aminoethoxy)-N2,N6-bis(4-(2-aminoethoxy)quinolin-2-yl)pyridine-2,6-dicarboxamide tris(2,2,2-trifluoroacetate)
InChi Key: CYYZQGUDHAKBIQ-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(C1=NC(C(NC2=NC3=CC=CC=C3C(OCCN)=C2)=O)=CC(OCCN)=C1)NC4=NC5=CC=CC=C5C(OCCN)=C4.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Pyridostatin (RR82) TFA is a G-quadruplex DNA stabilizing agent (Kd=490 nM). |
| In vitro activity: | For cell lines, the drug is cytotoxic, and this study, therefore, hypothesized that pyridostatin may be toxic for primary neurons as well. To test this, primary rat cortical cultures were transfected with the mApple construct (a red fluorescent protein). Pyridostatin or vehicle was added, and the mApple-expressing neurons were tracked for several days with an automated microscope. Loss of the red mApple fluorescence is a sensitive marker of neuronal death. This study found that treatment with pyridostatin substantially increased the risk of neuronal death in a dose-dependent manner (Fig. 1E). Notably, neurons exposed to pyridostatin retracted neurites before death (Fig. 1D), mimicking neuro-degenerative processes commonly observed in neurons that express ɑ-synuclein, mutant LRRK2 or mutant huntingtin. Reference: Aging (Albany NY). 2017 Sep; 9(9): 1957–1970. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636668/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 21.3 |
The following data is based on the product molecular weight 938.72 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Real-Hohn A, Zhu R, Ganjian H, Ibrahim N, Hinterdorfer P, Kowalski H, Blaas D. Catching Common Cold Virus with a Net: Pyridostatin Forms Filaments in Tris Buffer That Trap Viruses-A Novel Antiviral Strategy? Viruses. 2020 Jul 4;12(7):723. doi: 10.3390/v12070723. PMID: 32635420; PMCID: PMC7412420. 2. Moruno-Manchon JF, Koellhoffer EC, Gopakumar J, Hambarde S, Kim N, McCullough LD, Tsvetkov AS. The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons. Aging (Albany NY). 2017 Sep 12;9(9):1957-1970. doi: 10.18632/aging.101282. PMID: 28904242; PMCID: PMC5636668. |
| In vitro protocol: | 1. Real-Hohn A, Zhu R, Ganjian H, Ibrahim N, Hinterdorfer P, Kowalski H, Blaas D. Catching Common Cold Virus with a Net: Pyridostatin Forms Filaments in Tris Buffer That Trap Viruses-A Novel Antiviral Strategy? Viruses. 2020 Jul 4;12(7):723. doi: 10.3390/v12070723. PMID: 32635420; PMCID: PMC7412420. 2. Moruno-Manchon JF, Koellhoffer EC, Gopakumar J, Hambarde S, Kim N, McCullough LD, Tsvetkov AS. The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons. Aging (Albany NY). 2017 Sep 12;9(9):1957-1970. doi: 10.18632/aging.101282. PMID: 28904242; PMCID: PMC5636668. |
| In vivo protocol: | TBD |
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.
6: Müller S, Sanders DA, Di Antonio M, Matsis S, Riou JF, Rodriguez R, Balasubramanian S. Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells. Org Biomol Chem. 2012 Aug 28;10(32):6537-46. doi: 10.1039/c2ob25830g. Epub 2012 Jul 13. PubMed PMID: 22790277; PubMed Central PMCID: PMC3700226.
7: Mergny JL. Alternative DNA structures: G4 DNA in cells: itae missa est? Nat Chem Biol. 2012 Feb 15;8(3):225-6. doi: 10.1038/nchembio.793. PubMed PMID: 22337092.
8: Rodriguez R, Miller KM, Forment JV, Bradshaw CR, Nikan M, Britton S, Oelschlaegel T, Xhemalce B, Balasubramanian S, Jackson SP. Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. Nat Chem Biol. 2012 Feb 5;8(3):301-10. doi: 10.1038/nchembio.780. PubMed PMID: 22306580; PubMed Central PMCID: PMC3433707.
9: Mela I, Kranaster R, Henderson RM, Balasubramanian S, Edwardson JM. Demonstration of ligand decoration, and ligand-induced perturbation, of G-quadruplexes in a plasmid using atomic force microscopy. Biochemistry. 2012 Jan 17;51(2):578-85. doi: 10.1021/bi201600g. Epub 2012 Jan 6. PubMed PMID: 22225525.
10: Koirala D, Dhakal S, Ashbridge B, Sannohe Y, Rodriguez R, Sugiyama H, Balasubramanian S, Mao H. A single-molecule platform for investigation of interactions between G-quadruplexes and small-molecule ligands. Nat Chem. 2011 Aug 28;3(10):782-7. doi: 10.1038/nchem.1126. PubMed PMID: 21941250; PubMed Central PMCID: PMC3277938.
11: McCauley MJ, Williams MC. Single-molecule biophysics: untying a nanoscale knot. Nat Chem. 2011 Sep 23;3(10):754-5. doi: 10.1038/nchem.1159. PubMed PMID: 21941242.
