Denufosol

Summary

Denufosol (CHEMBL507282) is a phase-3 clinical-stage small molecule targeting P2RY2 and P2RY4.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (P2RY2, P2RY4)
• Chemistry: 773.3 Da · C18H27N5O21P4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL507282
Name	Denufosol
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9875516
Molecular formula	C18H27N5O21P4
Molecular weight	773.3
InChIKey	FPNPSEMJLALQSA-MIYUEGBISA-N

SMILES: C1[C@@H]([C@H](O[C@H]1N2C=CC(=NC2=O)N)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

IUPAC name: [[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-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

Also known as: Denufosol, INS-37217, INS37217, DENUFOSOL

Parent form; salt/anhydrous children: CHEMBL1767407

Patent coverage: 84 distinct patent families (199 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	6.7	1%	P41231
P2RY4	P2Y4 receptor	Full agonist	6.1	0%	P51582

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

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P2RY2	6.85	EC50	140	nM	CHEMBL_ACT_2350102
P2RY4	6.85	EC50	140	nM	CHEMBL_ACT_2350137
P2RY2	6.66	EC50	220	nM	CHEMBL_ACT_3105613
P2RY2	6.57	EC50	270	nM	CHEMBL_ACT_1821121
P2RY6	6.02	EC50	950	nM	CHEMBL_ACT_2350174

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

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 0.

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
DIQUAFOSOL	ChEMBL	Phase 4 (approved)	P2RY2, P2RY4
DIQUAFOSOL TETRASODIUM	ChEMBL	Phase 4 (approved)	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