T3DB: Ibuprofen

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (15)XML

Targets (15)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:16 UTC

Update Date

2014-12-24 20:25:54 UTC

Accession Number

T3D2970

Identification

Common Name

Ibuprofen

Class

Small Molecule

Description

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Act-3, Advil, Brufen, Motrin, Nuprin, and Nurofen. It is used for relief of symptoms of arthritis, primary dysmenorrhoea, and fever; Ibuprofen is an NSAID which is believed to work through inhibition of cyclooxygenase (COX), thus inhibiting prostaglandin synthesis. There are at least 2 variations of cyclooxygenase (COX-1 and COX-2), ibuprofen inhibits both COX-1 and COX-2. It appears that its analgesic, antipyretic, and anti-inflammatory activity are achieved principally through COX-2 inhibition; whereas COX-1 inhibition is responsible for its unwanted effects on platelet aggregation and the GI mucosa. As with other NSAIDs, ibuprofen inhibits platelet aggregation, but is not used therapeutically for this action since it is a minor and reversible effect. -- Wikipedia.

Compound Type

Analgesic
Analgesic, Non-Narcotic
Anti-Inflammatory Agent
Anti-Inflammatory Agent, Non-Steroidal
Cyclooxygenase Inhibitor
Drug
Food Toxin
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(+-)-2-(P-Isobutylphenyl)propionic acid
(+-)-alpha-Methyl-4-(2-methylpropyl)benzeneacetic acid
(+-)-Ibuprofen
(+-)-P-Isobutylhydratropic acid
(4-Isobutylphenyl)-alpha-methylacetic acid
(RS)-ibuprofen
2-(4-Isobutylphenyl)propanoic acid
4-Isobutylhydratropic acid
Act-3
Actiprofen
Adex
Adran
Advil
Advil Liqui-Gels
Aktren
Alges-X
Algoflex
Algofren
Alivium
alpha-(4-Isobutylphenyl)propionate
alpha-(4-Isobutylphenyl)propionic acid
alpha-(P-Isobutylphenyl)propionic acid
alpha-p-Isobutylphenylpropionate
alpha-p-Isobutylphenylpropionic acid
Amibufen
Anco
Anflagen
Apsifen
Artofen
Betagesic
Betaprofen
Bluton
Bonifen
Brufen
Brufort
Buburone
Bugesic
Buprovil
Burana
Butylenin
Caldolor
Calprofen
Cap-Profen
Children's Advil
Children's Elixsure
Children's Ibuprofen
Children's Motrin
Dalsy
Dismenol
Diverin
Dolgin
Dolgirid
Dolgit
Dolo-dolgit
Dolofort
Doloraz
Dolormin
Dorival
Duralbuprofen
Ebufac
EmuProfen
Epobron
Espidifen
Eve
Femadon
Fenbid
Fenpaed
Finalflex
Galprofen
Haltran
Herron Blue
i-profen
Ibalgin
IBU
Ibu-attritin
IBU-Ratiopharm
Ibu-Vivimed
Ibuflam
Ibugel
Ibugesic
IbuHEXAL
Ibuleve
Ibum
Ibumax
Ibumetin
Ibumidol
Ibupain
Ibuprocin
Ibuprom
Ibuprophen
Ibuprosyn
Ibuprox
Ibustar
Ibutid
Ibux
Ibuxin
Inabrin
Inoven
Ipren
Junior Strength Advil
Junior Strength Ibuprofen
Junior Strength Motrin
Kratalgin
Lamidon
Lebrufen
Liptan
Lotem
Medicol
Medipren
Midol IB
Motrin
Mynosedin
Mypaid
Myprodol
Narfen
Naron Ace
Neobrufen
NeoProfen
Nobfen
Nobgen
Norvectan
Nuprin
Nureflex
Nurofen
Orbifen
p-Isobutyl-2-phenylpropionate
p-Isobutyl-2-phenylpropionic acid
p-Isobutylhydratropate
p-Isobutylhydratropic acid
Panafen
Para-isobutylhydratropic acid
Pediaprofen
Perifar
Profin
Ranfen
Rapidol
Ratiodolor
Rimafen
Roidenin
Rufen
Salvarina
Seclodin
Solpaflex
Speedpain NANO
Spidifen
Suspren
Tabalon
Tefin
Trendar
Unafen
Upfen
Urem

Chemical Formula

C₁₃H₁₈O₂

Average Molecular Mass

206.281 g/mol

Monoisotopic Mass

206.131 g/mol

CAS Registry Number

15687-27-1

IUPAC Name

2-[4-(2-methylpropyl)phenyl]propanoic acid

Traditional Name

ibuprofen, (+-)-

SMILES

CC(C)CC1=CC=C(C=C1)C(C)C(O)=O

InChI Identifier

InChI=1/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)

InChI Key

InChIKey=HEFNNWSXXWATRW-UHFFFAOYNA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as phenylpropanoic acids. Phenylpropanoic acids are compounds with a structure containing a benzene ring conjugated to a propanoic acid.

Kingdom

Organic compounds

Super Class

Phenylpropanoids and polyketides

Class

Phenylpropanoic acids

Sub Class

Not Available

Direct Parent

Phenylpropanoic acids

Alternative Parents

Substituents

2-phenylpropanoic-acid
P-cymene
Aromatic monoterpenoid
Monocyclic monoterpenoid
Monoterpenoid
Phenylpropane
Monocyclic benzene moiety
Benzenoid
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organooxygen compound
Carbonyl group
Organic oxygen compound
Hydrocarbon derivative
Organic oxide
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

monocarboxylic acid (CHEBI:5855 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Adipose Tissue
Adrenal Cortex
Adrenal Gland
Bladder
Epidermis
Fibroblasts
Intestine
Kidney
Muscle
Myelin
Nerve Cells
Neuron
Pancreas
Placenta
Platelet
Prostate
Skeletal Muscle
Spleen
Stratum Corneum
Testes

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	75-77.5°C
Boiling Point	Not Available
Solubility	21 mg/L (at 25°C)
LogP	3.97

Predicted Properties

Property	Value	Source
Water Solubility	0.068 g/L	ALOGPS
logP	3.5	ALOGPS
logP	3.84	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	4.85	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	37.3 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	60.73 m³·mol⁻¹	ChemAxon
Polarizability	23.76 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)	splash10-02t9-1910000000-23f448d7be7d5cc35682	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)	splash10-02t9-1910000000-cbe52d63986b68a2cec0	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)	splash10-00di-9300000000-cc259b7768023e4cdba8	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-03di-3910000000-618880f8fd7b8ec3d473	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-02t9-1910000000-23f448d7be7d5cc35682	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-02t9-1910000000-cbe52d63986b68a2cec0	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9300000000-cc259b7768023e4cdba8	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0296-3900000000-497aad6d6a3e7af1ac0a	2017-08-28	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0309-8940000000-13dc492b216fb21dde05	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)	splash10-03di-0910000000-90bf6813134491c9fbfd	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)	splash10-001i-9800000000-56f599abc462380b648c	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI RMU-6E) , Positive	splash10-03di-3910000000-618880f8fd7b8ec3d473	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0006-0497000000-fa397d6ffd29da116900	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0a4i-0690000000-f598b8bee69a6b62e817	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-03di-1900000000-f1b7a986fee133d97eb1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-03di-0920000000-aa36b3244e32560bb9d5	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0900000000-5542c131f02b637029d8	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-03di-9200000000-5de1fac09e33bce1cc34	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Negative	splash10-0a4i-0900000000-c254195738a6348894be	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0900000000-d4b4b28d0bf1144854c3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Negative	splash10-0a4i-0900000000-5f5841ab0d19d92f329f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-03dl-7900000000-811cee3d7fc26d62724a	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-1970000000-50ac0f9eaf22b22ff57f	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0bti-2910000000-a5804838ebd627fea205	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0pb9-4900000000-a5b30d0a96d30db5ea4a	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0490000000-27a27175d7bf2807ff33	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-08fr-1940000000-f33172b037148de8a091	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-02ha-5900000000-ebc408aaffe3ab58a6a3	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0bti-0930000000-d13739453cc1a7af3307	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0bud-2910000000-db9b1bc4f7d1e33abb3c	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9510000000-6eaaec80d704e4b4603c	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0090000000-5535f56d1e770e37902d	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-08fr-0900000000-1aedbd14d6db0c13aa63	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014i-0900000000-9537810cacf26548c24a	2021-09-23	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-03xr-3900000000-e20ef3c30496e17720ba	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, CDCl₃, experimental)	Not Available	2012-12-05	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 50.32 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, CDCl₃, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Oral. ~ 80% absorbed from GI tract

Time to reach peak plasma concentration = 47 minutes (suspension), 62 minutes (chewable tablets), 120 minutes (conventional tablets)

Mechanism of Toxicity

The exact mechanism of action of ibuprofen is unknown. Ibuprofen is a non-selective inhibitor of cyclooxygenase, an enzyme invovled in prostaglandin synthesis via the arachidonic acid pathway. Its pharmacological effects are believed to be due to inhibition cylooxygenase-2 (COX-2) which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the more pharmacologically active enantiomer.

Metabolism

R-enanatiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer in vivo. Metablized by oxidation to 2 inactive metabolites: (+)-2[4'-(2-hydroxy-2-methylpropyl)phenyl]propionic acid and (+)-2-[4'-(2-carboxypropyl)phenyl]propionic acid. Very small amounts of 1-hydroxyibuprofen and 3-hydroxyibuprofen have been recovered from urine. Cytochrome P450 2C9 is the major catalyst in the formation of oxidative metabolites. Oxidative metabolites may be conjugated to glucuronide prior to excretion. Route of Elimination: Ibuprofen is rapidly metabolized and eliminated in the urine. Half Life: 2-4 hours

Toxicity Values

LD50: 1255mg/kg (Oral, Mouse) (6)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis and osteoarthritis. May be used to treat mild to moderate pain and for the management of dysmenorrhea. May be used to reduce fever. Has been used with some success for treating ankylosing spondylitis, gout and psoriatic arthritis. May reduce pain, fever and inflammation of pericarditis. May be used IV with opiates to relieve moderate to severe pain. Ibuprofen lysine may be used IV to treat patent ductus arteriosus (PDA) in premature neonates.

Minimum Risk Level

Not Available

Health Effects

Infrequent adverse effects include: oesophageal ulceration, heart failure, hyperkalaemia, renal impairment, confusion, and bronchospasm.[Wikipedia]

Symptoms

Side effects: May cause peripheral edema and fluid retention. Use caution in patients with congestive heart failure or severe uncontrolled hypertension. May cause dyspepsia, heartburn, nausea, vomiting, anorexia, diarrhea, constipation, stomatitis, flatulence, bloating, epigastric pain, and abdominal pain. Peptic ulcer and GI bleeding have been reported. May also cause dizziness, headache and nervousness. Acute renal failure accompanied by acute tubular necrosis has been reported. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).

Treatment

In cases of acute overdosage, the stomach should be emptied by vomiting or lavage, though little drug will likely be recovered if more than an hour has elapsed since ingestion. Because the drug is acidic and is excreted in the urine, it is theoretically beneficial to administer alkali and induce diuresis. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption and reabsorption of Ibuprofen tablets. (26)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

5855

BioCyc ID

CARBOXYPHENYLAMINO-DEOXYRIBULOSE-P

CTD ID

Not Available

Stitch ID

Ibuprofen

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Ibuprofen

References

Synthesis Reference

http://en.wikipedia.org/wiki/Ibuprofen#Synthesis

MSDS

Link

General References

Zawada ET Jr: Renal consequences of nonsteroidal antiinflammatory drugs. Postgrad Med. 1982 May;71(5):223-30. [7041104 ]
Townsend KP, Pratico D: Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005 Oct;19(12):1592-601. [16195368 ]
Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A: Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol. 2005 Dec;58(6):963-7. [16240369 ]
Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K: Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol. 1989 Jul;27(7):324-8. [2777420 ]
Bergner T, Przybilla B: Photosensitization caused by ibuprofen. J Am Acad Dermatol. 1992 Jan;26(1):114-6. [1531054 ]
Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Dill J, Patel AR, Yang XL, Bachoo R, Powell CM, Li S: A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. J Neurosci. 2010 Jan 20;30(3):963-72. doi: 10.1523/JNEUROSCI.5045-09.2010. [20089905 ]
Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M, Rossi C: Development of mucoadhesive patches for buccal administration of ibuprofen. J Control Release. 2004 Sep 14;99(1):73-82. [15342182 ]
Whitlam JB, Brown KF, Crooks MJ, Room GF: Transsynovial distribution of ibuprofen in arthritic patients. Clin Pharmacol Ther. 1981 Apr;29(4):487-92. [7471614 ]
Al-Saidan SM: Transdermal self-permeation enhancement of ibuprofen. J Control Release. 2004 Nov 24;100(2):199-209. [15544868 ]
Albert KS, Gernaat CM: Pharmacokinetics of ibuprofen. Am J Med. 1984 Jul 13;77(1A):40-6. [6465162 ]
Alam I, Ferrell LD, Bass NM: Vanishing bile duct syndrome temporally associated with ibuprofen use. Am J Gastroenterol. 1996 Aug;91(8):1626-30. [8759674 ]
Townsend RJ, Benedetti TJ, Erickson SH, Cengiz C, Gillespie WR, Gschwend J, Albert KS: Excretion of ibuprofen into breast milk. Am J Obstet Gynecol. 1984 May 15;149(2):184-6. [6720796 ]
Horn AC, Jarrett SW: Ibuprofen-induced aseptic meningitis in rheumatoid arthritis. Ann Pharmacother. 1997 Sep;31(9):1009-11. [9296242 ]
Van Overmeire B, Allegaert K, Casaer A, Debauche C, Decaluwe W, Jespers A, Weyler J, Harrewijn I, Langhendries JP: Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2004 Nov 27-Dec 3;364(9449):1945-9. [15567010 ]
Castillo M, Smith PC: Disposition and reactivity of ibuprofen and ibufenac acyl glucuronides in vivo in the rhesus monkey and in vitro with human serum albumin. Drug Metab Dispos. 1995 May;23(5):566-72. [7587932 ]
Hockertz S, Heckenberger R, Emmendorffer A, Muller M: Influence of ibuprofen on the infection with Listeria monocytogenes. Arzneimittelforschung. 1995 Jan;45(1):104-7. [7893261 ]
Day RO, Williams KM, Graham GG, Lee EJ, Knihinicki RD, Champion GD: Stereoselective disposition of ibuprofen enantiomers in synovial fluid. Clin Pharmacol Ther. 1988 May;43(5):480-7. [3365913 ]
Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ: Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6. [11832356 ]
Laffi G, Daskalopoulos G, Kronborg I, Hsueh W, Gentilini P, Zipser RD: Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac. Gastroenterology. 1986 Jan;90(1):182-7. [3079594 ]
Goldenberg NA, Jacobson L, Manco-Johnson MJ: Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med. 2005 Apr 5;142(7):506-9. [15809462 ]
Yao M, Zhou W, Sangha S, Albert A, Chang AJ, Liu TC, Wolfe MM: Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer. Clin Cancer Res. 2005 Feb 15;11(4):1618-28. [15746067 ]
Jabor VA, Lanchote VL, Bonato PS: Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography. Electrophoresis. 2002 Sep;23(17):3041-7. [12207314 ]
Salas-Herrera IG, Pearson RM, Turner P: Concentration of ibuprofen in cervical mucus. J Pharm Pharmacol. 1991 Feb;43(2):142-4. [1672904 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. Prostaglandin G/H synthase 2

General Function:: Prostaglandin-endoperoxide synthase activity
Specific Function:: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
Gene Name:: PTGS2
Uniprot ID:: P35354
Molecular Weight:: 68995.625 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	9.9 uM	Not Available	BindingDB 50009859
Inhibitory	>10 uM	Not Available	BindingDB 50009859
IC50	0.1 uM	Not Available	BindingDB 50009859
IC50	1.1 uM	Not Available	BindingDB 50009859
IC50	1.35 uM	Not Available	BindingDB 50009859
IC50	1.4 uM	Not Available	BindingDB 50009859
IC50	6.2 uM	Not Available	BindingDB 50009859
IC50	8 uM	Not Available	BindingDB 50009859
IC50	30 uM	Not Available	BindingDB 50009859
IC50	36 uM	Not Available	BindingDB 50009859
IC50	80 uM	Not Available	BindingDB 50009859

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [12852704 ]
Ouellet M, Falgueyret JP, Percival MD: Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms. Biochem J. 2004 Feb 1;377(Pt 3):675-84. [14510637 ]
Gallego-Sandin S, Novalbos J, Rosado A, Gisbert JP, Galvez-Mugica MA, Garcia AG, Pajares JM, Abad-Santos F: Effect of ibuprofen on cyclooxygenase and nitric oxide synthase of gastric mucosa: correlation with endoscopic lesions and adverse reactions. Dig Dis Sci. 2004 Sep;49(9):1538-44. [15481334 ]
Murphey LJ, Williams MK, Sanchez SC, Byrne LM, Csiki I, Oates JA, Johnson DH, Morrow JD: Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem. 2004 Nov 15;334(2):266-75. [15494133 ]
Sanchez-Fidalgo S, Martin-Lacave I, Illanes M, Motilva V: Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect of a selective cox-2 inhibitor. Eur J Pharmacol. 2004 Nov 28;505(1-3):187-94. [15556152 ]
Kolasa T, Brooks CD, Rodriques KE, Summers JB, Dellaria JF, Hulkower KI, Bouska J, Bell RL, Carter GW: Nonsteroidal anti-inflammatory drugs as scaffolds for the design of 5-lipoxygenase inhibitors. J Med Chem. 1997 Feb 28;40(5):819-24. [9057869 ]
Abdellatif KR, Chowdhury MA, Dong Y, Das D, Yu G, Velazquez C, Suresh MR, Knaus EE: Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-carboxymethylphenyl)-1-(4-methanesulfonylphenyl)-3-trifluoromethyl-1H-pyrazo le and its aminosulfonyl analog: Synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem. 2009 Jul 15;17(14):5182-8. doi: 10.1016/j.bmc.2009.05.046. Epub 2009 May 27. [19500994 ]
Chowdhury MA, Abdellatif KR, Dong Y, Das D, Yu G, Velazquez CA, Suresh MR, Knaus EE: Synthesis and biological evaluation of salicylic acid and N-acetyl-2-carboxybenzenesulfonamide regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore: dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6855-61. doi: 10.1016/j.bmcl.2009.10.083. Epub 2009 Oct 23. [19884005 ]
Chowdhury MA, Abdellatif KR, Dong Y, Yu G, Huang Z, Rahman M, Das D, Velazquez CA, Suresh MR, Knaus EE: Celecoxib analogs possessing a N-(4-nitrooxybutyl)piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridin-4-yl nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1324-9. doi: 10.1016/j.bmcl.2010.01.014. Epub 2010 Jan 11. [20097072 ]
Yu G, Praveen Rao PN, Chowdhury MA, Abdellatif KR, Dong Y, Das D, Velazquez CA, Suresh MR, Knaus EE: Synthesis and biological evaluation of N-difluoromethyl-1,2-dihydropyrid-2-one acetic acid regioisomers: dual inhibitors of cyclooxygenases and 5-lipoxygenase. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2168-73. doi: 10.1016/j.bmcl.2010.02.040. Epub 2010 Feb 13. [20202839 ]
Abdellatif KR, Chowdhury MA, Velazquez CA, Huang Z, Dong Y, Das D, Yu G, Suresh MR, Knaus EE: Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4544-9. doi: 10.1016/j.bmcl.2010.06.022. Epub 2010 Jun 8. [20576432 ]
Abdellatif KR, Huang Z, Chowdhury MA, Kaufman S, Knaus EE: A diazen-1-ium-1,2-diolated nitric oxide donor ester prodrug of 3-(4-hydroxymethylphenyl)-4-(4-methanesulfonylphenyl)-5H-furan-2-one: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett. 2011 Jul 1;21(13):3951-6. doi: 10.1016/j.bmcl.2011.05.017. Epub 2011 May 14. [21641217 ]
Jain S, Tran S, El Gendy MA, Kashfi K, Jurasz P, Velazquez-Martinez CA: Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs. J Med Chem. 2012 Jan 26;55(2):688-96. doi: 10.1021/jm200973j. Epub 2012 Jan 10. [22148253 ]
Bhardwaj A, Kaur J, Sharma SK, Huang Z, Wuest F, Knaus EE: Hybrid fluorescent conjugates of COX-2 inhibitors: search for a COX-2 isozyme imaging cancer biomarker. Bioorg Med Chem Lett. 2013 Jan 1;23(1):163-8. doi: 10.1016/j.bmcl.2012.10.131. Epub 2012 Nov 9. [23200247 ]
Viegas A, Manso J, Corvo MC, Marques MM, Cabrita EJ: Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR. J Med Chem. 2011 Dec 22;54(24):8555-62. doi: 10.1021/jm201090k. Epub 2011 Nov 29. [22091869 ]
Huang Z, Velazquez CA, Abdellatif KR, Chowdhury MA, Reisz JA, DuMond JF, King SB, Knaus EE: Ethanesulfohydroxamic acid ester prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs): synthesis, nitric oxide and nitroxyl release, cyclooxygenase inhibition, anti-inflammatory, and ulcerogenicity index studies. J Med Chem. 2011 Mar 10;54(5):1356-64. doi: 10.1021/jm101403g. Epub 2011 Jan 31. [21280601 ]
Harrak Y, Rosell G, Daidone G, Plescia S, Schillaci D, Pujol MD: Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system. Bioorg Med Chem. 2007 Jul 15;15(14):4876-90. Epub 2007 May 3. [17517512 ]
Wilkerson WW, Copeland RA, Covington M, Trzaskos JM: Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition. J Med Chem. 1995 Sep 29;38(20):3895-901. [7562922 ]
Janusz JM, Young PA, Ridgeway JM, Scherz MW, Enzweiler K, Wu LI, Gan L, Darolia R, Matthews RS, Hennes D, Kellstein DE, Green SA, Tulich JL, Rosario-Jansen T, Magrisso IJ, Wehmeyer KR, Kuhlenbeck DL, Eichhold TH, Dobson RL, Sirko SP, Farmer RW: New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent. J Med Chem. 1998 Mar 26;41(7):1112-23. [9544211 ]
Janusz JM, Young PA, Scherz MW, Enzweiler K, Wu LI, Gan L, Pikul S, McDow-Dunham KL, Johnson CR, Senanayake CB, Kellstein DE, Green SA, Tulich JL, Rosario-Jansen T, Magrisso IJ, Wehmeyer KR, Kuhlenbeck DL, Eichhold TH, Dobson RL: New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations of the dihydrobenzofuran ring. J Med Chem. 1998 Mar 26;41(7):1124-37. [9544212 ]
Janusz JM, Young PA, Ridgeway JM, Scherz MW, Enzweiler K, Wu LI, Gan L, Chen J, Kellstein DE, Green SA, Tulich JL, Rosario-Jansen T, Magrisso IJ, Wehmeyer KR, Kuhlenbeck DL, Eichhold TH, Dobson RL: New cyclooxygenase-2/5-lipoxygenase inhibitors. 3. 7-tert-butyl-2, 3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations at the 5 position. J Med Chem. 1998 Aug 27;41(18):3515-29. [9719605 ]
Favia AD, Habrant D, Scarpelli R, Migliore M, Albani C, Bertozzi SM, Dionisi M, Tarozzo G, Piomelli D, Cavalli A, De Vivo M: Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor. J Med Chem. 2012 Oct 25;55(20):8807-26. doi: 10.1021/jm3011146. Epub 2012 Oct 8. [23043222 ]
Hieke M, Ness J, Steri R, Dittrich M, Greiner C, Werz O, Baumann K, Schubert-Zsilavecz M, Weggen S, Zettl H: Design, synthesis, and biological evaluation of a novel class of gamma-secretase modulators with PPARgamma activity. J Med Chem. 2010 Jun 24;53(12):4691-700. doi: 10.1021/jm1003073. [20503989 ]
Hieke M, Ness J, Steri R, Greiner C, Werz O, Schubert-Zsilavecz M, Weggen S, Zettl H: SAR studies of acidic dual gamma-secretase/PPARgamma modulators. Bioorg Med Chem. 2011 Sep 15;19(18):5372-82. doi: 10.1016/j.bmc.2011.08.003. Epub 2011 Aug 6. [21873070 ]
Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. [9626023 ]
Riendeau D, Percival MD, Brideau C, Charleson S, Dube D, Ethier D, Falgueyret JP, Friesen RW, Gordon R, Greig G, Guay J, Mancini J, Ouellet M, Wong E, Xu L, Boyce S, Visco D, Girard Y, Prasit P, Zamboni R, Rodger IW, Gresser M, Ford-Hutchinson AW, Young RN, Chan CC: Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther. 2001 Feb;296(2):558-66. [11160644 ]

Target Details

2. Prostaglandin G/H synthase 1

General Function:: Prostaglandin-endoperoxide synthase activity
Specific Function:: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:: PTGS1
Uniprot ID:: P23219
Molecular Weight:: 68685.82 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	6.3 uM	Not Available	BindingDB 50009859
IC50	6.9 uM	Not Available	BindingDB 50009859

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [12852704 ]
Patrignani P: Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease. Thromb Res. 2003 Jun 15;110(5-6):281-6. [14592549 ]
Gupta K, Kaub CJ, Carey KN, Casillas EG, Selinsky BS, Loll PJ: Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors. Bioorg Med Chem Lett. 2004 Feb 9;14(3):667-71. [14741265 ]
Martic M, Tatic I, Markovic S, Kujundzic N, Kostrun S: Synthesis, biological activity and molecular modeling studies of novel COX-1 inhibitors. Eur J Med Chem. 2004 Feb;39(2):141-51. [14987823 ]
Hillarp A: [Acetylsalicylic acid resistance--clinical diagnosis with unclear mechanism]. Lakartidningen. 2004 Nov 4;101(45):3504-6, 3508-9. [15575422 ]
Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Harrak Y, Rosell G, Daidone G, Plescia S, Schillaci D, Pujol MD: Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system. Bioorg Med Chem. 2007 Jul 15;15(14):4876-90. Epub 2007 May 3. [17517512 ]

Target Details

3. Serum albumin

General Function:: Toxic substance binding
Specific Function:: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:: ALB
Uniprot ID:: P02768
Molecular Weight:: 69365.94 Da

References

Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, Kragh-Hansen U, Otagiri M: Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. AAPS PharmSciTech. 2000 May 14;1(2):E12. [14727845 ]
Ahlfors CE: Effect of ibuprofen on bilirubin-albumin binding. J Pediatr. 2004 Mar;144(3):386-8. [15001951 ]
Fabriciova G, Sanchez-Cortes S, Garcia-Ramos JV, Miskovsky P: Surface-enhanced Raman spectroscopy study of the interaction of the antitumoral drug emodin with human serum albumin. Biopolymers. 2004 May-Jun 5;74(1-2):125-30. [15137109 ]
Ito H, Ishiwata S, Kosaka T, Nakashima R, Takeshita H, Negoro S, Maeda M, Ikegawa S: Enantioselective immunorecognition of protein modification with optically active ibuprofen using polyclonal antibody. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jun 25;806(1):11-7. [15149605 ]
Melillo M, Gun'ko VM, Tennison SR, Mikhalovska LI, Phillips GJ, Davies JG, Lloyd AW, Kozynchenko OP, Malik DJ, Streat M, Mikhalovsky SV: Structural characteristics of activated carbons and ibuprofen adsorption affected by bovine serum albumin. Langmuir. 2004 Mar 30;20(7):2837-51. [15835161 ]

Target Details

4. Peroxisome proliferator-activated receptor gamma

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:: PPARG
Uniprot ID:: P37231
Molecular Weight:: 57619.58 Da

References

Dill J, Patel AR, Yang XL, Bachoo R, Powell CM, Li S: A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. J Neurosci. 2010 Jan 20;30(3):963-72. doi: 10.1523/JNEUROSCI.5045-09.2010. [20089905 ]
Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1997 Feb 7;272(6):3406-10. [9013583 ]

Target Details

5. Aldo-keto reductase family 1 member C3

General Function:: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function:: Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
Gene Name:: AKR1C3
Uniprot ID:: P42330
Molecular Weight:: 36852.89 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	33 uM	Not Available	BindingDB 50009859

References

Gobec S, Brozic P, Rizner TL: Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5170-5. Epub 2005 Sep 23. [16183274 ]

Target Details

6. Apoptosis regulator Bcl-2

General Function:: Ubiquitin protein ligase binding
Specific Function:: Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
Gene Name:: BCL2
Uniprot ID:: P10415
Molecular Weight:: 26265.66 Da

References

Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR, Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012 Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. [22668799 ]

Target Details

7. Arachidonate 5-lipoxygenase

General Function:: Iron ion binding
Specific Function:: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:: ALOX5
Uniprot ID:: P09917
Molecular Weight:: 77982.595 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	17 uM	Not Available	BindingDB 50009859

References

Kolasa T, Brooks CD, Rodriques KE, Summers JB, Dellaria JF, Hulkower KI, Bouska J, Bell RL, Carter GW: Nonsteroidal anti-inflammatory drugs as scaffolds for the design of 5-lipoxygenase inhibitors. J Med Chem. 1997 Feb 28;40(5):819-24. [9057869 ]

Target Details

8. Cystic fibrosis transmembrane conductance regulator

General Function:: Pdz domain binding
Specific Function:: Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Gene Name:: CFTR
Uniprot ID:: P13569
Molecular Weight:: 168139.895 Da

References

Devor DC, Schultz BD: Ibuprofen inhibits cystic fibrosis transmembrane conductance regulator-mediated Cl- secretion. J Clin Invest. 1998 Aug 15;102(4):679-87. [9710435 ]

Target Details

9. Cytochrome P450 2C9

General Function:: Steroid hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular Weight:: 55627.365 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	50 uM	Not Available	BindingDB 50009859

References

Rao S, Aoyama R, Schrag M, Trager WF, Rettie A, Jones JP: A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions. J Med Chem. 2000 Jul 27;43(15):2789-96. [10956186 ]

Target Details

10. Fatty acid-binding protein, intestinal

General Function:: Transporter activity
Specific Function:: FABP are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to unsaturated long-chain fatty acids. FABP2 may also help maintain energy homeostasis by functioning as a lipid sensor.
Gene Name:: FABP2
Uniprot ID:: P12104
Molecular Weight:: 15207.165 Da

References

Velkov T, Chuang S, Wielens J, Sakellaris H, Charman WN, Porter CJ, Scanlon MJ: The interaction of lipophilic drugs with intestinal fatty acid-binding protein. J Biol Chem. 2005 May 6;280(18):17769-76. Epub 2005 Feb 18. [15722357 ]

Target Details

11. Peroxisome proliferator-activated receptor alpha

General Function:: Zinc ion binding
Specific Function:: Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:: PPARA
Uniprot ID:: Q07869
Molecular Weight:: 52224.595 Da

References

Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1997 Feb 7;272(6):3406-10. [9013583 ]

Target Details

12. Solute carrier family 22 member 6

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:: SLC22A6
Uniprot ID:: Q4U2R8
Molecular Weight:: 61815.78 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	8 uM	Not Available	BindingDB 50009859

References

Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. [10991954 ]

Target Details

13. Solute carrier family 22 member 8

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:: SLC22A8
Uniprot ID:: Q8TCC7
Molecular Weight:: 59855.585 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	1170 uM	Not Available	BindingDB 50009859

References

Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [12130730 ]

Target Details

14. Thrombomodulin

General Function:: Transmembrane signaling receptor activity
Specific Function:: Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
Gene Name:: THBD
Uniprot ID:: P07204
Molecular Weight:: 60328.72 Da

References

Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR, Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012 Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. [22668799 ]

Target Details

15. Tissue-type plasminogen activator

General Function:: Serine-type endopeptidase activity
Specific Function:: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration.
Gene Name:: PLAT
Uniprot ID:: P00750
Molecular Weight:: 62916.495 Da

References

Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR, Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012 Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. [22668799 ]

Ibuprofen (T3D2970)

Structure for T3D2970: Ibuprofen

Targets

Binding/Activity Constants

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