Naproxcinod

Summary

Naproxcinod (CHEMBL2103831) is a phase-3 clinical-stage small-molecule non-steroidal anti-inflammatory drug (ATC M01AE18) targeting PTGS1 and PTGS2; indicated across 5 conditions including rheumatic disorder and osteoarthritis, hip.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: M01AE18
• Targets: 2 (PTGS1, PTGS2)
• Indications: 5 conditions
• Clinical trials: 7
• Chemistry: 347.4 Da · C18H21NO6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103831
Name	Naproxcinod
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9884642
ChEBI	CHEBI:76254
ATC	M01AE18
Molecular formula	C18H21NO6
Molecular weight	347.4
InChIKey	AKFJWRDCWYYTIG-ZDUSSCGKSA-N

SMILES: C[C@@H](C1=CC2=C(C=C1)C=C(C=C2)OC)C(=O)OCCCCO[N+](=O)[O-]

IUPAC name: 4-nitrooxybutyl (2S)-2-(6-methoxynaphthalen-2-yl)propanoate

ChEBI definition: A carboxylic ester obtained by formal condensation of the carboxy group of naproxen with the hydroxy group of 4-(nitrooxy)butanol. A cyclooxygenase-inhibiting nitric oxide donator that is metabolised to naproxen and a nitric oxide donating moiety, effective in treatment of osteoarthritis.

Pharmacological roles (ChEBI): non-steroidal anti-inflammatory drug, non-narcotic analgesic, prodrug, nitric oxide donor, EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor.

Also known as: AR-P900758XX, AZD-3582, AZD3582, HCT 3012, HCT-3012, HCT3012, Naproxcinod, Naproxen-n-butyl nitrate, Nitronaproxen, NAPROXCINOD

Patent coverage: 99 distinct patent families (258 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 228 (88%) of the total. 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
PTGS1	COX-1	Inhibition		0%	P23219
PTGS2	COX-2	Inhibition		0%	P35354

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 2 target gene(s): PTGS1, PTGS2.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	2	PTGS1, PTGS2
COX reactions	1	PTGS1
Synthesis of 15-eicosatetraenoic acid derivatives	1	PTGS2
Interleukin-10 signaling	1	PTGS2
Interleukin-4 and Interleukin-13 signaling	1	PTGS2
Biosynthesis of DHA-derived SPMs	1	PTGS2
Biosynthesis of EPA-derived SPMs	1	PTGS2
Biosynthesis of DPAn-3 SPMs	1	PTGS2
Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives	1	PTGS2

Dominant GO biological processes

GO term	Targets
prostaglandin biosynthetic process	2
response to oxidative stress	2
regulation of blood pressure	2
cyclooxygenase pathway	2
regulation of cell population proliferation	2
long-chain fatty acid biosynthetic process	2
lipid metabolic process	2
fatty acid metabolic process	2
fatty acid biosynthetic process	2
prostaglandin metabolic process	2
prostanoid biosynthetic process	2
cellular oxidant detoxification	2
embryo implantation	1
response to nematode	1
response to selenium ion	1

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
rheumatic disorder	3	MONDO:0005554	EFO:0005755
osteoarthritis, hip	3	MONDO:0006629	EFO:1000786
osteoarthritis	3	MONDO:0005178	MONDO:0005178
liver disorder	1	MONDO:0005154	EFO:0001421
kidney failure	1	MONDO:0001106	EFO:1002048

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE1	4
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00541489	PHASE3	COMPLETED	Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Hip
NCT00542555	PHASE3	COMPLETED	Analgesic Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Knee
NCT00383487	PHASE2	TERMINATED	A Phase II Trial of Calcitriol and Naproxen in Patients With Recurrent Prostate Cancer
NCT00621881	PHASE1	COMPLETED	A Phase 1 Study to Compare the PK and Safety of Naproxcinod in Hepatic Impaired Patients and Matching Healthy Subjects
NCT00674856	PHASE1	COMPLETED	A Pharmacokinetics and Safety Study of Naproxcinod in Subjects With Impaired Renal Function
NCT00909519	PHASE1	COMPLETED	Effect of Repeated Dosing of Naproxcinod on Renal Hemodynamic and on Sodium Balance in Healthy Volunteers Before and After a Single Dose of Furosemide
NCT01404598	PHASE1	COMPLETED	Pharmacokinetics Study: Determination of Naproxcinod and Its Metabolites After Oral Administration in Male

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.

408 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
3,3’,4’,5-TETRACHLOROSALICYLANILIDE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ACEMETACIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ASPIRIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
BROMFENAC	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CAPSAICIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CAPTOPRIL	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CARPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CELECOXIB	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CIANIDANOL	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
DEXIBUPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
DEXKETOPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
DICLOFENAC	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
DOXORUBICIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ESFLURBIPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ETODOLAC	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ETORICOXIB	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
FLURBIPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
GLAFENINE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
IBUPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
KETOPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
KETOROLAC	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
LEVODOPA	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
LOXOPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
LUMIRACOXIB	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
MECLOFENAMIC ACID	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
MEFENAMIC ACID	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
MELOXICAM	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
MOFEZOLAC	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
MONOBENZONE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
NAPROXEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
NIMESULIDE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
OMADACYCLINE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
OXAPROZIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
PIROXICAM	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
PRIMAQUINE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
RANITIDINE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
ROFECOXIB	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
SELINEXOR	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
SUPROFEN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
TEGASEROD	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
TELOTRISTAT	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
TOLMETIN	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
TROGLITAZONE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
VALDECOXIB	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
VORTIOXETINE	ChEMBL	Phase 4 (approved)	PTGS1, PTGS2
CURCUMIN	ChEMBL	Phase 3	PTGS1, PTGS2
RESVERATROL	ChEMBL	Phase 3	PTGS1, PTGS2
CIMICOXIB	ChEMBL	Phase 2	PTGS1, PTGS2
DERACOXIB	ChEMBL	Phase 2	PTGS1, PTGS2
ENOFELAST	ChEMBL	Phase 2	PTGS1, PTGS2
FIROCOXIB	ChEMBL	Phase 2	PTGS1, PTGS2
FLUFENAMIC ACID	ChEMBL	Phase 2	PTGS1, PTGS2
LICOFELONE	ChEMBL	Phase 2	PTGS1, PTGS2
MAVACOXIB	ChEMBL	Phase 2	PTGS1, PTGS2
MIROPROFEN	ChEMBL	Phase 2	PTGS1, PTGS2
NIFLUMIC ACID	ChEMBL	Phase 2	PTGS1, PTGS2
PHENOTHIAZINE	ChEMBL	Phase 2	PTGS1, PTGS2