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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H22N4O23P4.4Na
Molecular Weight 878.2344
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIQUAFOSOL TETRASODIUM

SMILES

[Na+].[Na+].[Na+].[Na+].O[C@H]1[C@@H](O)[C@@H](O[C@@H]1COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N3C=CC(=O)NC3=O)N4C=CC(=O)NC4=O

InChI

InChIKey=OWTGMPPCCUSXIP-FNXFGIETSA-J
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.santeninc.com/newsroom/press-releases/10_04_DIQUAS.pdf | http://www.santen.com/en/therapeutic-areas/asia/dryeye/diquas/

Diquafosol, a dinucleotide Up4U, is an agonist for purinergic P2Y2 receptor. Diquafosol stimulated water and mucin secretion by acting on P2Y2 receptors on the conjunctival epithelial and goblet cell membrane and elevating intracellular calcium ion concentrations. The Japanese Ministry of Health, Labour and Welfare granted approval for DIQUAS Ophthalmic Solution 3% (diquafosol tetrasodium) for the treatment of dry eye.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 0.1 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
DIQUAS

Approved Use

DIQUAS Ophthalmic Solution 3% (generic name: diquafosol tetrasodium) should be used in patients diagnosed with dry eye, associated with keratoconjunctival epithelium disorders that accompany lacrimal fluid abnormality.

Launch Date

2010
PubMed

PubMed

TitleDatePubMed
The medicinal chemistry of the P2 receptor family.
2001
Ocular safety of INS365 ophthalmic solution: a P2Y(2) agonist in healthy subjects.
2001 Apr
Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study.
2001 Aug
Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model.
2001 Jan
Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates.
2001 Jan 22
Ocular safety of INS365 ophthalmic solution, a P2Y2 agonist, in patients with mild to moderate dry eye disease.
2002
Potency and duration of action of synthetic P2Y2 receptor agonists on Schirmer scores in rabbits.
2002
INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model.
2002 Aug
Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease.
2002 Dec 5
P2Y(2) receptor agonists: a new class of medication targeted at improved mucociliary clearance.
2002 May
Pharmacology of INS37217 [P(1)-(uridine 5')-P(4)- (2'-deoxycytidine 5')tetraphosphate, tetrasodium salt], a next-generation P2Y(2) receptor agonist for the treatment of cystic fibrosis.
2002 Sep
Diquafosol: DE 089, diquafosol tetrasodium, INS 365, INS 365 Ophthalmic, INS 365 Respiratory, KPY 998.
2003
Therapy for chronic obstructive pulmonary disease in the 21st century.
2003
Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits.
2003 Feb
Diquafosol tetrasodium. Inspire/Allergan/Santen.
2003 Nov
Diquafosol tetrasodium: a novel dry eye therapy.
2004 Jan
Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye.
2004 Nov
Recent advances in the management of ocular complications of Sjögren's syndrome.
2005 Jul
P2 receptors activated by uracil nucleotides--an update.
2006
New approaches in Sjögren's syndrome therapy.
2007 Mar
[A molecular marker for dry eye].
2007 Mar
Therapeutic targets in dry eye syndrome.
2008 Apr
Denufosol: a review of studies with inhaled P2Y(2) agonists that led to Phase 3.
2008 Aug
Topical application of nucleotides increase lysozyme levels in tears.
2008 Jun
Preliminary effects of oral uridine on the ocular surface in dry eye patients.
2009 Aug
Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y(4) receptor.
2011 Jun 23
Patents

Patents

EP2659894A1
2
JP2013227291A
2
US20060062787A1
2

Sample Use Guides

In Vivo Use Guide
DIQUAS Ophthalmic Solution 3% (generic name: diquafosol tetrasodium). Usually, instill 1 drop a time 6 times daily.
Route of Administration: Topical
In Vitro Use Guide
3% diquafosol tetrasodium had a significant, time-dependent, inhibitory effect on human corneal epithelial cells (HCEC) proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery.
Name Type Language
DIQUAFOSOL TETRASODIUM
MART.   USAN   WHO-DD  
USAN  
Official Name English
DIQUAFOSOL TETRASODIUM [MART.]
Common Name English
URIDINE, 5'-(PENTAHYDROGEN TETRAPHOSPHATE), P''' ->5'-ESTER WITH URIDINE, TETRASODIUM SALT
Common Name English
Diquafosol tetrasodium [WHO-DD]
Common Name English
DE-089
Code English
KPY-998
Code English
URIDINE(5')TETRAPHOSPHO(5')URIDINE TETRASODIUM SALT
Common Name English
DIQUAFOSOL SODIUM
JAN  
Common Name English
DIQUAFOSOL TETRASODIUM SALT [MI]
Common Name English
DIQUAFOSOL SODIUM [JAN]
Common Name English
INS365
Code English
DIQUAFOSOL TETRASODIUM [USAN]
Common Name English
DIQUAFOSOL TETRASODIUM SALT
MI  
Common Name English
INS 365
Code English
Classification Tree Code System Code
NCI_THESAURUS C78283
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
FDA ORPHAN DRUG 116998
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
Code System Code Type Description
MERCK INDEX
m4661
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY Merck Index
USAN
OO-03
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
CAS
211427-08-6
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
EVMPD
SUB32869
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
PUBCHEM
148196
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
FDA UNII
X8T9SBH9LL
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
NCI_THESAURUS
C65437
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
SMS_ID
100000126190
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
ChEMBL
CHEMBL221326
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
PRIMARY
CAS
266356-23-4
Created by admin on Fri Dec 15 16:21:22 GMT 2023 , Edited by admin on Fri Dec 15 16:21:22 GMT 2023
SUPERSEDED
ACTIVE MOIETY
Structure of DIQUAFOSOL
NIH
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