Denufosol tetrasodium

Denufosol tetrasodium (INS37217) is a long-acting P2Y2 receptor agonist, which exhibits an EC50 of ~10 μM for P2Y2 receptor activation.

Product information

CAS Number: 318250-11-2

Molecular Weight: 861.25

Formula: C18H23N5Na4O21P4

Chemical Name: [(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl sodium {[({[({[(2R,3S,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy}(sodiooxy)phosphoryl)oxy](sodiooxy)phosphoryl}oxy)(sodiooxy)phosphoryl]oxy}phosphonate

Smiles: NC1C=CN([C@H]2C[C@H](O)[C@@H](COP(=O)(OP(=O)(OP(=O)(OP(=O)(OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)N3C=CC(=O)NC3=O)O[Na])O[Na])O[Na])O[Na])O2)C(=O)N=1

InChiKey: PASYJVRFGUDDEW-WMUGRWSXSA-J

InChi: InChI=1S/C18H27N5O21P4.4Na/c19-11-1-3-22(17(28)20-11)13-5-8(24)9(40-13)6-38-45(30,31)42-47(34,35)44-48(36,37)43-46(32,33)39-7-10-14(26)15(27)16(41-10)23-4-2-12(25)21-18(23)29;;;;/h1-4,8-10,13-16,24,26-27H,5-7H2,(H,30,31)(H,32,33)(H,34,35)(H,36,37)(H2,19,20,28)(H,21,25,29);;;;/q;4*+1/p-4/t8-,9+,10+,13+,14+,15+,16+;;;;/m0..../s1

Technical Data

Appearance: Solid Power

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

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:

Denufosol tetrasodium can be maintained above the EC50 point for 6 to 8 hours on the airway surface of airway cultures. Denufosol produces a significant increase in airway surface layer (ASL) height, reflecting P2Y2 receptor–mediated fluid secretion, which is terminated rapidly, likely reflecting P2Y2 receptor desensitization. The secreted ASL is reabsorbed over time, despite the continued presence of Denufosol at values exceeding its EC50, albeit at a rate slower than without Denufosol exposure (compared to vehicle group). This latter finding is consistent with the observation that P2Y2 receptor-mediated inhibition of Na+ absorption may persist for larger intervals than P2Y2 receptor activation of Cl- secretion. Denufosol (INS37217) is a deoxycytidine-uridine dinucleotide with agonist activity at the P2Y2 receptor. In a concentration-dependent manner, Denufosol induces the mobilization of intracellular calcium in 1321N1 astrocytoma cells stably expressing human P2Y2 and P2Y4 receptors with EC50s of 0.22 and 0.8 μM, respectively. The efficacy of Denufosol is identical to that of UTP, indicating that Denufosol is a full agonist of P2Y2 and P2Y4 receptors. Denufosol is a weak agonist of P2Y6 receptors in which 100 μM Denufosol produces approximately 70% of the response observed with the natural agonist UDP.

In Vivo:

The P2Y2 receptor agonist Denufosol (INS37217) improves the rate of retinal reattachment in animal models of induced retinal detachment (RD), and has been shown to also significantly enhance the rate of ERG recovery in a mouse model of RD. The identification of genes modulated by Denufosol may allow further drug discovery for treating RD and edema. RD is induced in Balb/cJ mice by transvitreal subretinal injections of 1 μL saline or of 1 μL of 10 μM Denufosol/saline to cause detachment and to expedite the rate of recovery.

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