DIQUAFOSOL

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H26N4O23P4
Molecular Weight	790.3079
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cn([C@@]2([H])[C@@]([H])([C@@]([H])([C@@]([H])(COP(=O)(O)OP(=O)(O)OP(=O)(O)OP(=O)(O)OC[C@]3([H])[C@]([H])([C@]([H])([C@]([H])(n4ccc(nc4=O)O)O3)O)O)O2)O)O)c(=O)nc1O

InChI

InChIKey=NMLMACJWHPHKGR-NCOIDOBVSA-N

InChI=1S/C18H26N4O23P4/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)/t7-,8-,11-,12-,13-,14-,15-,16-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C18H26N4O23P4
Molecular Weight	790.3079
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18600475
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

Targets

Primary Target	Pharmacology	Condition	Potency
Purinergic receptor P2Y2 8 Target ID: CHEMBL4398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18600475	Agonist 2456		0.1 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21 Sources: http://www.santen.com/en/therapeutic-areas/asia/dryeye/diquas/	Primary		Approved 7997	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 1.27128961E12

PubMed

Title	Date	PubMed
The medicinal chemistry of the P2 receptor family.	2001	11774794
Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study.	2001 Aug	11477729
Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model.	2001 Jan	11133853
Potency and duration of action of synthetic P2Y2 receptor agonists on Schirmer scores in rabbits.	2002	12613918
Metabolism and transport of purinergic receptor agonists in rabbit conjunctival epithelial cells.	2002	12613917
INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model.	2002 Aug	12222766
Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease.	2002 Dec 5	12458155
P2Y(2) receptor agonists: a new class of medication targeted at improved mucociliary clearance.	2002 May	12010852
Novel noninvasive sensitive determination of tear volume changes in normal cats.	2002 Nov-Dec	12483025
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	12183642
Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits.	2003 Feb	12568851
Diquafosol tetrasodium. Inspire/Allergan/Santen.	2003 Nov	14758778
Molecule of the month. Diquafosol tetrasodium.	2003 Oct	14668951
Diquafosol tetrasodium: a novel dry eye therapy.	2004 Jan	14680452
Recent advances in the management of ocular complications of Sjögren's syndrome.	2005 Jul	15967078
P2 receptors activated by uracil nucleotides--an update.	2006	16475938
New approaches in Sjögren's syndrome therapy.	2007 Mar	20477108
[A molecular marker for dry eye].	2007 Mar	17357887
Therapeutic targets in dry eye syndrome.	2008 Apr	18560615
Denufosol: a review of studies with inhaled P2Y(2) agonists that led to Phase 3.	2008 Aug	18276176
Preliminary effects of oral uridine on the ocular surface in dry eye patients.	2009 Aug	19654956

Patents

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.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 07:18:17 UTC 2021` Edited by `admin` on `Sat Jun 26 07:18:17 UTC 2021`
Record UNII	7828VC80FJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIQUAFOSOL

Official Name

English

P1,P4-DI(URIDINE 5'-TETRAPHOSPHATE), TETRASODIUM SALT

Common Name

English

URIDINE, 5'-(PENTAHYDROGEN TETRAPHOSPHATE), P'''->5'-ESTER WITH URIDINE

Common Name

English

DIQUAFOSOL [MI]

Common Name

English

DIQUAFOSOL [INN]

Common Name

English

DIQUAFOSOL [WHO-DD]

Common Name

English

P1, P4-DI(URIDINE 5'-TETRAPHOSPHATE), TETRASODIUM SALT

Common Name

English

URIDINE(5')TETRAPHOSPHO(5')URIDINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78283