Diquafosol

Summary

Diquafosol (CHEMBL221326) is an approved small-molecule P2Y2 receptor agonist (ATC S01XA33) targeting P2RY2 and P2RY4; indicated across 1 condition including eye disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: S01XA33
• Targets: 2 (P2RY2, P2RY4)
• Indications: 1 condition
• Clinical trials: 8
• Chemistry: 790.3 Da · C18H26N4O23P4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL221326
Name	Diquafosol
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	148197
ChEBI	CHEBI:27791
ATC	S01XA33
Molecular formula	C18H26N4O23P4
Molecular weight	790.3
InChIKey	NMLMACJWHPHKGR-NCOIDOBVSA-N

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

IUPAC name: [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate

ChEBI definition: A pyrimidine ribonucleoside 5’-tetraphosphate compound having 5’-uridinyl residues at the P1- and P4-positions.

Pharmacological roles (ChEBI): P2Y2 receptor agonist.

Other ChEBI roles (chemical / environmental): mouse metabolite.

Also known as: Dicuafosol, Diquafosol, Diuridine tetraphosphate, INS-365, diuridine 5’,5’-tetraphosphate, INS-45973, DIQUAFOSOL

Parent form; salt/anhydrous children: CHEMBL1767408

Patent coverage: 178 distinct patent families (413 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
P2RY2	P2Y2 receptor	Full agonist	7	1%	P41231
P2RY4	P2Y4 receptor	Full agonist	6.4	0%	P51582

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: P2Y purinoceptor 4, P2Y purinoceptor 2, P2Y purinoceptor 6.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 17 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P2RY2	7.22	EC50	60	nM	CHEMBL_ACT_8031822
P2RY2	7.03	EC50	94.5	nM	CHEMBL_ACT_2513510
P2RY2	7	EC50	100	nM	CHEMBL_ACT_3105612
P2RY2	6.95	EC50	112	nM	CHEMBL_ACT_2513431
P2RY4	6.89	EC50	130	nM	CHEMBL_ACT_1821068
P2RY4	6.89	EC50	130	nM	CHEMBL_ACT_2350140
P2RY2	6.84	EC50	145	nM	CHEMBL_ACT_2513515
P2RY2	6.75	EC50	179	nM	CHEMBL_ACT_2513509
P2RY2	6.68	EC50	210	nM	CHEMBL_ACT_1821066
P2RY2	6.68	EC50	210	nM	CHEMBL_ACT_2350106
P2RY2	6.67	EC50	216	nM	CHEMBL_ACT_2513516
P2RY2	6.64	EC50	231	nM	CHEMBL_ACT_2513517
P2RY2	6.41	EC50	394	nM	CHEMBL_ACT_2513511
P2RY2	6.38	EC50	419	nM	CHEMBL_ACT_2513513
P2RY2	6.24	EC50	572	nM	CHEMBL_ACT_2513512
P2RY6	5.94	EC50	1160	nM	CHEMBL_ACT_2350177

Target pathways

Aggregated over 2 target gene(s): P2RY2, P2RY4.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
P2Y receptors	2	P2RY2, P2RY4
G alpha (q) signalling events	1	P2RY2
G alpha (i) signalling events	1	P2RY4
Surfactant metabolism	1	P2RY2
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	P2RY2

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
G protein-coupled purinergic nucleotide receptor signaling pathway	2
cellular response to ATP	2
signal transduction	2
intracellular monoatomic ion homeostasis	1
positive regulation of mucus secretion	1
blood vessel diameter maintenance	1
positive regulation of cytosolic calcium ion concentration	1
transepithelial chloride transport	1
cellular response to prostaglandin E stimulus	1

Indications & clinical

Indications

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE4	3
Not specified	3
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07397949	PHASE4	NOT_YET_RECRUITING	Rebamipide Versus Diquafosol for Perioperative Dry Eye in Cataract Surgery
NCT04668118	PHASE4	UNKNOWN	The Effect of 3% Diquafosol Ophthalmic Solution on Visual Display Terminal-associated Dry Eye
NCT07397936	PHASE4	COMPLETED	Rebamipide Versus Diquafosol and Cyclosporine for Perioperative Dry Eye in Cataract Surgery
NCT04548427	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of CKD-352
NCT06146881	PHASE2	UNKNOWN	Effectiveness of Diquafosol Prophylactic Therapy to Prevent Dry Eye Disease for Cataract Surgery Patients in Indonesia
NCT02608489	Not specified	COMPLETED	Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery
NCT04952987	Not specified	UNKNOWN	Dry Eye Management With 3% Diquafosol Before and After Cataract Surgery
NCT07122635	Not specified	COMPLETED	Effectiveness of Dry Eye Treatment With Diquafosol Sodium 3% After Phaco Surgery

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

Molecule	Source	Status	Shared targets
ADENOSINE	ChEMBL + PubChem	Phase 4 (approved)	P2RY2, P2RY4
DENUFOSOL	ChEMBL	Phase 3	P2RY2, P2RY4
DENUFOSOL TETRASODIUM	ChEMBL	Phase 3	P2RY2, P2RY4
URIDINE TRIPHOSPHATE	ChEMBL	Phase 3	P2RY2, P2RY4
ADENOSINE TRIPHOSPHATE	ChEMBL	Phase 2	P2RY2, P2RY4
SURAMIN	ChEMBL	Phase 3	P2RY2
Carbachol	PubChem	Approved	P2RY2
Indomethacin	PubChem	Approved	P2RY2