ROFECOXIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H14O4S
Molecular Weight	314.356
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=RZJQGNCSTQAWON-UHFFFAOYSA-N

InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3

HIDE SMILES / InChI

Molecular Formula	C17H14O4S
Molecular Weight	314.356
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Rofecoxib is a nonsteroidal anti-inflammatory drug which selectively inhibits COX-2 and subsequent prostaglandin synthesis. The drug was developed by Merk and approved by FDA in 1999 for relief of signs and symptoms of arthritis, acute pain in adults, and painful menstrual cycles under the name Vioxx. Later on Merck voluntarily withdrawn Vioxx from the market due to safety concerns (high risk of heart attack and stroke).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 196	Inhibitor 8,297		0.02 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hemophilic Arthropathy 1	Primary	Phase II 1,132	Unknown
Osteoarthritis 157	Palliative	Withdrawn	VIOXX
Rheumatoid arthritis 316	Palliative	Withdrawn	VIOXX
Acute pain 17	Primary	Withdrawn	VIOXX
Primary dysmenorrhea 16	Primary	Withdrawn	VIOXX
Migraine 103	Primary	Withdrawn	VIOXX

C_max

Value	Dose	Co-administered	Analyte	Population
321 ng/mL	25 mg 1 times / day multiple, oral		ROFECOXIB plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
4018 ng × h/mL	25 mg 1 times / day multiple, oral		ROFECOXIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
17 h	25 mg 1 times / day multiple, oral		ROFECOXIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
13%	25 mg 1 times / day multiple, oral		ROFECOXIB plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
12.5 mg 1 times / day steady, oral Recommended	unhealthy, 44-76 years n = 6	Disc. AE: Renal impairment...
50 mg 1 times / day steady, oral Studied dose	unhealthy, 44-76 years n = 33
25 mg 1 times / day steady, oral Recommended	unhealthy, 58–71years n = 1167	Disc. AE: Cardiac thrombosis... Other AEs: Cardiac thrombosis...
25 mg 1 times / day multiple, oral (max) Recommended	unhealthy, 66.8 years n = 2896	Disc. AE: Dyspepsia, Nausea...
25 mg 1 times / day multiple, oral (typical) Recommended	unhealthy, adult n = 2200000	Disc. AE: Death... Other AEs: Hemorrhage, Edema...

Showing 1 to 5 of 5 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Renal impairment	grade 1, 1 patient Disc. AE	12.5 mg 1 times / day steady, oral Recommended	unhealthy, 44-76 years n = 6
Cardiac thrombosis	16 patients	25 mg 1 times / day steady, oral Recommended	unhealthy, 58–71years n = 1167
Cardiac thrombosis	grade 5, 4 patients Disc. AE	25 mg 1 times / day steady, oral Recommended	unhealthy, 58–71years n = 1167
Dizziness	2.1% Disc. AE	25 mg 1 times / day multiple, oral (max) Recommended	unhealthy, 66.8 years n = 2896
Nausea	2.4% Disc. AE	25 mg 1 times / day multiple, oral (max) Recommended	unhealthy, 66.8 years n = 2896

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1,587	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 CYP2E1 882	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A8 283 UGT1A9 380 UGT2B7 389 UGT2B15 203

Drug as perpetrator

Show entries

Target	Modality	Activity	Clinical evidence
CYP3A4 1,925	inducer 1,573	likely	weak (co-administration study)
CYP2C9 1,819	inhibitor 3,277	no
CYP2D6 1,891	inhibitor 3,277	no
CYP2E1 970	inhibitor 3,277	no
CYP3A4 1,925	inhibitor 3,277	no

Showing 1 to 5 of 6 entries

Previous1 2Next

Drug as victim

Show entries

Target	Modality	Activity	Metabolite
UGT2B15 203	substrate 3,367	major	5-hydroxyrofecoxib 1
UGT1A1 418	substrate 3,367	weak	5-hydroxyrofecoxib 1
UGT1A3 422	substrate 3,367	weak	5-hydroxyrofecoxib 1
UGT1A4 347	substrate 3,367	weak	5-hydroxyrofecoxib 1
UGT1A6 307	substrate 3,367	weak	5-hydroxyrofecoxib 1

Showing 1 to 5 of 8 entries

Previous1 2Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8887	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8887
ChemicalBook	CB6327130	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6327130
MolPort	MolPort-000-883-878	https://www.molport.com/shop/molecule-link/MolPort-000-883-878
MolPort	MolPort-006-817-786	https://www.molport.com/shop/molecule-link/MolPort-006-817-786
Selleck Chemicals	rofecoxib-vioxx	http://www.selleckchem.com/products/rofecoxib-vioxx.html

Showing 1 to 5 of 7 entries

Previous1 2Next

PubMed

Show entries

Title	Date	PubMed
Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis.	1999 Jun 22	10377455
Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions.	1999 Nov 26	10594344
Potential adverse effects of cyclooxygenase-2 inhibition: evidence from animal models of inflammation.	2001	11437671
Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis.	2001	11398914
Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice.	2001 Apr	11315375

Showing 1 to 5 of 34 entries

Previous1 2 3 4 5 6 7Next

Patents

Sample Use Guides

In Vivo Use Guide

Osteoarthritis: the recommended starting dose of rofecoxib (VIOXX) is 12.5 mg once daily. Rheumatoid Arthritis: the recommended dose is 50 mg once daily. Management of Acute Pain and Treatment of Primary Dysmenorrhea: the recommended dose is 50 mg once daily. Acute Treatment of Migraine Attacks with or without aura: the recommended dose is 25 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

THP-1 human macrophages and peripheral blood mononuclear cells were incubated with rofecoxib (at 5, 10, 25 uM). The presence of rofecoxib (at high concentrations) significantly decreased expression of 27-hydroxylase and ABCA1, interfering with normal cholesterol outflow from macrophages.