Rofecoxib

Summary

Rofecoxib (CHEMBL122) is an approved small-molecule cyclooxygenase 2 inhibitor (ATC M01AH02) targeting PTGS2; indicated across 13 conditions including rheumatic disorder and osteoarthritis, knee.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: M01AH02
• Targets: 1 (PTGS2)
• Indications: 13 conditions
• Clinical trials: 29
• Chemistry: 314.4 Da · C17H14O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL122
Name	Rofecoxib
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	5090
ChEBI	CHEBI:8887
ATC	M01AH02
Molecular formula	C17H14O4S
Molecular weight	314.4
InChIKey	RZJQGNCSTQAWON-UHFFFAOYSA-N

SMILES: CS(=O)(=O)C1=CC=C(C=C1)C2=C(C(=O)OC2)C3=CC=CC=C3

IUPAC name: 3-(4-methylsulfonylphenyl)-4-phenyl-2H-furan-5-one

ChEBI definition: A butenolide that is furan-2(5H)-one substituted by a phenyl group at position 3 and by a p-(methylsulfonyl)phenyl group at position 4. A selective cyclooxygenase 2 inhibitor, it was used from 1999 to 2004 for the treatment of ostoarthritis, but was withdrawn following concerns about an associated increased risk of heart attack and stroke.

Pharmacological roles (ChEBI): cyclooxygenase 2 inhibitor, non-steroidal anti-inflammatory drug, analgesic.

Also known as: M01AH02, MK-0966, MK-966, MK0966, NSC-720256, NSC-758705, Rofecoxib, TRM-201, TRM201, Vioxx, rofecoxib, refocoxib

Parent form; salt/anhydrous children: CHEMBL4465601, CHEMBL5171570

Patent coverage: 15,604 distinct patent families (66,907 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
PTGS2	COX-2	Inhibition	6.5	0%	P35354

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Inositol monophosphatase 1, 5-hydroxytryptamine receptor 1A, Prostaglandin G/H synthase 1, Prostaglandin G/H synthase 2, Adenosine receptor A3, Melanocortin receptor 4, Prostaglandin G/H synthase 1, Prostaglandin G/H synthase 2, Prostaglandin G/H synthase 2, Gamma-aminobutyric acid receptor subunit alpha-1.

Bioactivity

ChEMBL activities: 96 potent at pChembl ≥ 5 of 131 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PTGS2	9	IC50	1	nM	CHEMBL_ACT_553676
PTGS2	7.92	IC50	12	nM	CHEMBL_ACT_120988
Q05769	7.92	IC50	12	nM	CHEMBL_ACT_1507833
PTGS2	7.82	IC50	15	nM	CHEMBL_ACT_1610390
PTGS2	7.7	IC50	20	nM	CHEMBL_ACT_1008305
PTGS2	7.7	IC50	20	nM	CHEMBL_ACT_1076183
MT-CO2	7.7	IC50	20	nM	CHEMBL_ACT_19078174
PTGS2	7.7	IC50	20	nM	CHEMBL_ACT_764471
PTGS2	7.7	IC50	20	nM	CHEMBL_ACT_890759
PTGS2	7.7	IC50	20	nM	CHEMBL_ACT_894801
PTGS2	7.6	IC50	25	nM	CHEMBL_ACT_1610391
PTGS2	7.6	IC50	25	nM	CHEMBL_ACT_28834763
PTGS2	7.57	IC50	27	nM	CHEMBL_ACT_25709925
PTGS2	7.5	IC50	32	nM	CHEMBL_ACT_1454031
PTGS2	7.5	IC50	32	nM	CHEMBL_ACT_2718025
PTGS2	7.24	IC50	57	nM	CHEMBL_ACT_652257
Q05769	7.22	IC50	60	nM	CHEMBL_ACT_15107583
PTGS2	7.13	IC50	74.5	nM	CHEMBL_ACT_2620122
PTGS2	6.97	IC50	107	nM	CHEMBL_ACT_2717939
PTGS2	6.92	IC50	120	nM	CHEMBL_ACT_1864245
PTGS2	6.81	IC50	156	nM	CHEMBL_ACT_6320456
PTGS2	6.77	IC50	170	nM	CHEMBL_ACT_12102858
PTGS2	6.77	IC50	170	nM	CHEMBL_ACT_7931220
PTGS2	6.71	IC50	196	nM	CHEMBL_ACT_1303927
PTGS2	6.68	IC50	211	nM	CHEMBL_ACT_2097476
PTGS2	6.68	IC50	210	nM	CHEMBL_ACT_94670
PTGS2	6.58	IC50	260	nM	CHEMBL_ACT_2718064
PTGS2	6.55	IC50	280	nM	CHEMBL_ACT_120995
PTGS2	6.55	IC50	280	nM	CHEMBL_ACT_713261
PTGS2	6.54	IC50	292	nM	CHEMBL_ACT_2097416

Target pathways

Aggregated over 1 target gene(s): PTGS2.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Synthesis of 15-eicosatetraenoic acid derivatives	1	PTGS2
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	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	1
response to oxidative stress	1
embryo implantation	1
regulation of blood pressure	1
response to nematode	1
response to selenium ion	1
positive regulation of vascular endothelial growth factor production	1
cyclooxygenase pathway	1
lipoxygenase pathway	1
positive regulation of prostaglandin biosynthetic process	1
positive regulation of fever generation	1
prostaglandin secretion	1
regulation of cell population proliferation	1
long-chain fatty acid biosynthetic process	1
positive regulation of nitric oxide biosynthetic process	1

Indications & clinical

Indications

13 indications (1 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	4	MONDO:0005554	EFO:0005755
osteoarthritis, knee	3	MONDO:0005416	EFO:0004616
gastric neoplasm	3	MONDO:0021085	EFO:0003897
colorectal adenoma	3	MONDO:0005484	EFO:0005406
arthropathy	3	MONDO:0006816	HP:0003040
osteoarthritis	3	MONDO:0005178	MONDO:0005178
colorectal neoplasm	3	MONDO:0005335	MONDO:0005575
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
brain neoplasm	1	MONDO:0021211	EFO:0003833
paraganglioma	1	MONDO:0000448	EFO:1000453

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 29.

Phase distribution

Phase	Trials
PHASE3	16
PHASE4	5
PHASE2/PHASE3	3
PHASE2	2
Not specified	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00140920	PHASE4	TERMINATED	A Study of Rofecoxib in the Treatment of Post-Operative Pain After Total Knee Joint Replacement (0966-259)
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00261586	PHASE4	COMPLETED	A Safety Trial to Compare Different Analgesics in Combination With Low Dose Aspirin to Study Their Bleeding Properties and Their Effects on the Stomach
NCT00637988	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross Over
NCT00657449	PHASE4	TERMINATED	A Double-blind, Double-dummy, Multicenter, Randomized Study of the Efficacy and Tolerability of Valdecoxib 40 mg Versus Rofecoxib 50 mg in Treating the Symptoms of Ankle Sprain
NCT00004845	PHASE2/PHASE3	COMPLETED	A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer’s Disease (NSAID Study)
NCT00031863	PHASE3	COMPLETED	Rofecoxib After Surgery in Treating Patients With Stage II or Stage III Colorectal Cancer
NCT00060476	PHASE3	COMPLETED	Treatment With MK0966 for the Prevention of Prostate Cancer (0966-201)
NCT00092300	PHASE3	COMPLETED	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-181)(COMPLETED)
NCT00092313	PHASE3	COMPLETED	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-182)
NCT00092326	PHASE3	COMPLETED	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-183)
NCT00092339	PHASE3	COMPLETED	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-190)(COMPLETED)
NCT00092352	PHASE3	COMPLETED	A Study of Two Approved Drugs in Patients With Osteoarthritis (0966-219)
NCT00092365	PHASE3	COMPLETED	A Study of Two Approved Drugs in Patients With Osteoarthritis (0966-220)(COMPLETED)
NCT00092378	PHASE3	COMPLETED	A Study of Two Approved Drugs in the Treatment of Post-Bunionectomy Surgery Pain (0966-234)(COMPLETED)
NCT00140933	PHASE3	TERMINATED	A Study to Evaluate Rofecoxib Versus Placebo and Diclofenac in Patients With Acute Painful Rotator Cuff Syndrome
NCT00164892	PHASE3	UNKNOWN	Selective COX-II Inhibitor as an Adjuvant Therapy in Patients With Resectable Advanced Stomach Cancer ( Histological Staging ≥ T2N1) - A Multi-Centre Prospective Randomised Controlled Trial
NCT00165048	PHASE3	UNKNOWN	Selective COX-II Inhibitor as a Palliative Therapy in Patients With R1 or R2 Resection for Disseminated Stomach Cancer - A Multi-Centre Prospective Randomized Controlled Trial
NCT00385606	PHASE2/PHASE3	COMPLETED	Study of Rofecoxib and Prolonged Constant Infusion of Gemcitabine in the Polychemotherapy Treatment of Advanced NSCLC
NCT00390260	PHASE3	COMPLETED	Effect of Rofecoxib and a Narcotic Analgesic to Treat Pain Following Arthroscopic Surgery (0966-179)(COMPLETED)
NCT00568295	PHASE3	COMPLETED	A Four-Week Study Comparing Acetaminophen Extended Release and Rofecoxib in the Treatment of Osteoarthritis of the Knee
NCT00637949	PHASE3	COMPLETED	Safety of Lumiracoxib in Patients With Osteoarthritis
NCT00844727	PHASE2/PHASE3	TERMINATED	Coxib-inhibition of Duodenal Polyp Growth in FAP
NCT04684511	PHASE3	TERMINATED	Rofecoxib Efficacy and Safety Evaluation Trial in Hemophilic Arthropathy
NCT00026819	PHASE2	COMPLETED	Rofecoxib to Prevent Pain After Third Molar (Wisdom Tooth) Extraction
NCT00050362	PHASE2	COMPLETED	Rofecoxib and Bupivacaine to Prevent Pain After Third Molar (Wisdom Tooth) Extraction
NCT00038389	PHASE1	TERMINATED	Study of Vioxx and Radiation Therapy for Brainstem Glioma
NCT00263094	Not specified	COMPLETED	An End to the Yom Kippur (and Ramadan) Headache
NCT01762891	Not specified	COMPLETED	CI(R)CA : Coumadin Interaction With Rofecoxib, Celecoxib and Acetaminophen

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	PTGS2
3,3’,4’,5-TETRACHLOROSALICYLANILIDE	ChEMBL	Phase 4 (approved)	PTGS2
ABEMACICLIB	ChEMBL	Phase 4 (approved)	PTGS2
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	PTGS2
ACEMETACIN	ChEMBL	Phase 4 (approved)	PTGS2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	PTGS2
ACETYLCYSTEINE	ChEMBL	Phase 4 (approved)	PTGS2
ACRIVASTINE	ChEMBL	Phase 4 (approved)	PTGS2
AMODIAQUINE	ChEMBL	Phase 4 (approved)	PTGS2
AMPHOTERICIN B	ChEMBL	Phase 4 (approved)	PTGS2
AMSACRINE	ChEMBL	Phase 4 (approved)	PTGS2
ANISINDIONE	ChEMBL	Phase 4 (approved)	PTGS2
APOMORPHINE	ChEMBL	Phase 4 (approved)	PTGS2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	PTGS2
ASPIRIN	ChEMBL	Phase 4 (approved)	PTGS2
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	PTGS2
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	PTGS2
BEPRIDIL	ChEMBL	Phase 4 (approved)	PTGS2
BIPERIDEN	ChEMBL	Phase 4 (approved)	PTGS2
BROMFENAC	ChEMBL	Phase 4 (approved)	PTGS2
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	PTGS2
CALCITRIOL	ChEMBL	Phase 4 (approved)	PTGS2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PTGS2
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PTGS2
CAPSAICIN	ChEMBL	Phase 4 (approved)	PTGS2
CAPTOPRIL	ChEMBL	Phase 4 (approved)	PTGS2
CARPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
CEFAZOLIN	ChEMBL	Phase 4 (approved)	PTGS2
CEFTIZOXIME	ChEMBL	Phase 4 (approved)	PTGS2
CELECOXIB	ChEMBL	Phase 4 (approved)	PTGS2
CEPHRADINE	ChEMBL	Phase 4 (approved)	PTGS2
CIANIDANOL	ChEMBL	Phase 4 (approved)	PTGS2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	PTGS2
CRIZOTINIB	ChEMBL	Phase 4 (approved)	PTGS2
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	PTGS2
DESERPIDINE	ChEMBL	Phase 4 (approved)	PTGS2
DEXIBUPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
DEXKETOPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
DICLOFENAC	ChEMBL	Phase 4 (approved)	PTGS2
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	PTGS2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	PTGS2
DOXORUBICIN	ChEMBL	Phase 4 (approved)	PTGS2
EPINEPHRINE	ChEMBL	Phase 4 (approved)	PTGS2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	PTGS2
ESFLURBIPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
ETODOLAC	ChEMBL	Phase 4 (approved)	PTGS2
ETORICOXIB	ChEMBL	Phase 4 (approved)	PTGS2
FLUPIRTINE	ChEMBL	Phase 4 (approved)	PTGS2
FLURBIPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
FLUVASTATIN	ChEMBL	Phase 4 (approved)	PTGS2
FOLIC ACID	ChEMBL	Phase 4 (approved)	PTGS2
GLAFENINE	ChEMBL	Phase 4 (approved)	PTGS2
HALOPERIDOL	ChEMBL	Phase 4 (approved)	PTGS2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	PTGS2
IBUPROFEN	ChEMBL	Phase 4 (approved)	PTGS2
ICOSAPENT ETHYL	ChEMBL	Phase 4 (approved)	PTGS2
INDAPAMIDE	ChEMBL	Phase 4 (approved)	PTGS2
INDOCYANINE GREEN ACID FORM	ChEMBL	Phase 4 (approved)	PTGS2
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PTGS2
IPRONIAZID	ChEMBL	Phase 4 (approved)	PTGS2