Physicochemical Properties
| Molecular Formula | C37H35F3N10O9 |
| Molecular Weight | 820.7306 |
| Exact Mass | 706.26119 |
| CAS # | 2444713-88-4 |
| PubChem CID | 134828255 |
| Appearance | Off-white to light yellow solid powder |
| LogP | -1.1 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 19 |
| Rotatable Bond Count | 16 |
| Heavy Atom Count | 59 |
| Complexity | 1190 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(C1=CC(NC(C2=CC(OCC3N=NN(CCC(=O)O)C=3)=CC(C(=O)NC3C=C(OCCN)C4C=CC=CC=4N=3)=N2)=O)=NC2C=CC=CC1=2)CCN.O=C(C(F)(F)F)O |
| InChi Key | WTHDBHUUPVHFQX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C35H34N10O7.C2HF3O2/c36-10-13-50-29-17-31(39-25-7-3-1-5-23(25)29)41-34(48)27-15-22(52-20-21-19-45(44-43-21)12-9-33(46)47)16-28(38-27)35(49)42-32-18-30(51-14-11-37)24-6-2-4-8-26(24)40-32;3-2(4,5)1(6)7/h1-8,15-19H,9-14,20,36-37H2,(H,46,47)(H,39,41,48)(H,40,42,49);(H,6,7) |
| Chemical Name | 3-[4-[[2,6-bis[[4-(2-aminoethoxy)quinolin-2-yl]carbamoyl]pyridin-4-yl]oxymethyl]triazol-1-yl]propanoic acid;2,2,2-trifluoroacetic acid |
| Synonyms | Carboxy pyridostatin trifluoroacetate salt; 2444713-88-4; Carboxy pyridostatin (trifluoroacetate salt);3-(4-(((2,6-Bis((4-(2-aminoethoxy)quinolin-2-yl)carbamoyl)pyridin-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)propanoic acid; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | G-quadruplex |
| ln Vitro | G-quadruplexes are pervasive nucleic acid secondary structures in mammalian genomes and transcriptomes that regulate gene expression and genome duplication. Small molecule ligands that modify the stability of G-quadruplexes are widely studied in cancer, but whether G-quadruplex ligands can also be used to manipulate cell function under normal development and homeostatic conditions is largely unexplored. Here we show that two related G-quadruplex ligands (pyridostatin and carboxypyridostatin) can reduce proliferation of adult neural stem cell and progenitor cells derived from the adult mouse subventricular zone both in vitro and in vivo. Studies with neurosphere cultures show that pyridostatin reduces proliferation by a mechanism associated with DNA damage and cell death. By contrast, selectively targeting RNA G-quadruplex stability with carboxypyridostatin diminishes proliferation through a mechanism that promotes cell cycle exit and the production of oligodendrocyte progenitors. The ability to generate oligodendrocyte progenitors by targeting RNA G-quadruplex stability, however, is dependent on the cellular environment. Together, these findings show that ligands that can selectively stabilize RNA G-quadruplexes are an important, new class of molecular tool for neural stem and progenitor cell engineering, whereas ligands that target DNA G-quadruplexes have limited utility due to their toxicity.[1] |
| Enzyme Assay | The pyridostatin (PDS) represents the lead compound of a family of G-quadruplex (G4) stabilizing synthetic small molecules based on a N,N'-bis(quinolinyl)pyridine-2,6-dicarboxamide scaffold. Its mechanism of action involves the induction of telomere dysfunction by competing for binding with telomere-associated proteins, such as human POT1. Recently, through a template-directed "in situ" click chemistry approach, a PDS derivative, the carboxypyridostatin (cPDS), was discovered. It has the peculiarity to exhibit high molecular specificity for RNA over DNA G4, while PDS is a good generic RNA and DNA G4-interacting small molecule. Structural data on the binding modes of these compounds are not available, and the selectivity mode of cPDS toward TERRA G4 is unknown too. Therefore, this work is aimed at rationalizing the selectivity of cPDS versus TERRA G4 by means of molecular dynamics and docking simulations, coupled to better understand the binding mode of these compounds to telomeric G4 structures. The comprehensive analysis of cPDS binding mode and its conformational behavior demonstrates the importance of the ligand conformation properties coupled with a remarkable solvation contribution. This work is expected to provide valuable clues for further rational design of novel and selective TERRA G4 binders.[2] |
| References |
[1]. Manipulating Adult Neural Stem and Progenitor Cells with G-Quadruplex Ligands. ACS Chem Neurosci. 2020;11(10):1504-1518. [2]. Molecular recognition of a carboxy pyridostatin toward G-quadruplex structures: Why does it prefer RNA? Chem Biol Drug Des. 2017 Nov;90(5):919-925. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 100 mg/mL (121.84 mM) H2O : 60 mg/mL (73.11 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2184 mL | 6.0921 mL | 12.1843 mL | |
| 5 mM | 0.2437 mL | 1.2184 mL | 2.4369 mL | |
| 10 mM | 0.1218 mL | 0.6092 mL | 1.2184 mL |