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Diquafosol tetrasodium (Diquas; INS-365) is a novel and potent P2Y2 purinoceptor agonist that stimulates fluid and mucin secretion on the ocular surface, and is used as a topical treatment of dry eye disease.
Physicochemical Properties
| Molecular Formula | C18H22N4O23P4-4.4[NA+] |
| Molecular Weight | 878.234680000001 |
| Exact Mass | 877.92 |
| Elemental Analysis | C, 24.62; H, 2.53; N, 6.38; Na, 10.47; O, 41.90; P, 14.11 |
| CAS # | 211427-08-6 |
| Related CAS # | 211427-08-6 (tetrasodium); 59985-21-6 |
| PubChem CID | 148196 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 23 |
| Rotatable Bond Count | 14 |
| Heavy Atom Count | 53 |
| Complexity | 1460 |
| Defined Atom Stereocenter Count | 8 |
| SMILES | C1=CN(C(=O)NC1=O)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)([O-])OP(=O)([O-])OP(=O)([O-])OP(=O)([O-])OC[C@@H]3[C@H]([C@H]([C@@H](O3)N4C=CC(=O)NC4=O)O)O)O)O.[Na+].[Na+].[Na+].[Na+] |
| InChi Key | OWTGMPPCCUSXIP-FNXFGIETSA-J |
| InChi Code | InChI=1S/C18H26N4O23P4.4Na/c23-9-1-3-21(17(29)19-9)15-13(27)11(25)7(41-15)5-39-46(31,32)43-48(35,36)45-49(37,38)44-47(33,34)40-6-8-12(26)14(28)16(42-8)22-4-2-10(24)20-18(22)30;;;;/h1-4,7-8,11-16,25-28H,5-6H2,(H,31,32)(H,33,34)(H,35,36)(H,37,38)(H,19,23,29)(H,20,24,30);;;;/q;4*+1/p-4/t7-,8-,11-,12-,13-,14-,15-,16-;;;;/m1..../s1 |
| Chemical Name | tetrasodium;[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate |
| Synonyms | INS-365; DE-089; KPY-998; INS 365; DE 089; KPY 998; INS365; DE089; KPY998; Diquas |
| 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 | P2Y2 receptor |
| ln Vitro | Cell viability was significantly reduced after treatment with 30% diquafosol tetrasodium for 1 hour and 10% and 20% diquafosol tetrasodium for 6 hours. 24 hours after monolayer cell damage, wound healing was significantly aggravated by 3% diquafosol tetrasodium and 0.3% HCEC [1]. |
| ln Vivo | In a mini-dry eye model, the P2Y2 agonist tetraphosphonate was found to restore surface health based on increased tear production, corneal epithelial resistance, and the release of glycoproteins from goblet cells. Beginning in week 2 and continuing for 2 weeks, the maximum decrease in dye-extrasigma rate was approximately 50% at doses as low as 1% of diquafosol tetrasodium [2]. Diquafosol tetrasodium can significantly interfere with potential damage when the concentration exceeds 0.1% w/v [3]. |
| Cell Assay | The MTT assay is used to assess the viability of human corneal epithelial cells (HCECs). Diquafosol (100%, 20%, or 30% diluted) or DMEM (100 mL) is added to controls when the cells are subconfluent. To get rid of the medications, plates are cleaned three times using PBS after one, six, and twenty-four hours. After a 24-hour incubation period, cell viability is assessed. Next, each well receives an addition of MTT. After 4 hours of dark incubation at 37°C, the samples are removed from the media. The precipitates are reconstituted in DMSO. At 570 nm, absorbances are measured using a plate reader[1]. |
| Animal Protocol | Rats: The Schirmer test score was at least 50% lower in an SD rat dry eye model after exorbital lacrimal gland extraction. INS365-containing eye drops are administered six times a day for the following four weeks at concentrations ranging from 0.03% to 3.0% after eight weeks, at which point there have been noticeable increases in corneal epithelial permeability. Measurements of fluorescein penetrance obtained with a modified anterior fluorometer at 1, 2, and 4 weeks following initial application are used to assess the function of the corneal barrier. The periodic acid-Schiff reagent (PAS)-stained area is assessed in histologic sections of the bulbar and tarsal conjunctiva following INS365 application[2]. |
| References |
[1]. Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells. Korean J Physiol Pharmacol. 2017 Mar;21(2):189-195. [2]. Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001 Jan;42(1):96-100. [3]. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002 Aug;18(4):363-70. |
Solubility Data
| Solubility (In Vitro) |
H2O: ~100 mg/mL (~113.9 mM) DMSO: ~1 mg/mL (~1.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (113.87 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1387 mL | 5.6933 mL | 11.3865 mL | |
| 5 mM | 0.2277 mL | 1.1387 mL | 2.2773 mL | |
| 10 mM | 0.1139 mL | 0.5693 mL | 1.1387 mL |