DIQUAFOSOL

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H26N4O23P4
Molecular Weight	790.3071
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=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	790.3071
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 9 Target ID: CHEMBL4398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18600475	Agonist 2678		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 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

Title	Date	PubMed
Ocular safety of INS365 ophthalmic solution: a P2Y(2) agonist in healthy subjects.	2001 Apr	11324984
Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model.	2001 Jan	11133853
Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates.	2001 Jan 22	11206448
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
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
Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva.	2004 Mar-Apr	15017104
P2 receptors activated by uracil nucleotides--an update.	2006	16475938
New approaches in Sjögren's syndrome therapy.	2007 Mar	20477108
Therapeutic targets in dry eye syndrome.	2008 Apr	18560615
Topical application of nucleotides increase lysozyme levels in tears.	2008 Jun	19668714
Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y(4) receptor.	2011 Jun 23	21528910

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 Dec 16 15:59:21 GMT 2023` Edited by `admin` on `Sat Dec 16 15:59:21 GMT 2023`
Record UNII	7828VC80FJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIQUAFOSOL

Official Name

English

DIURIDINE TETRAPHOSPHATE

Common 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

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

Common Name

English

Diquafosol [WHO-DD]

Common Name

English

URIDINE(5')TETRAPHOSPHO(5')URIDINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78283