T3DB: Flurbiprofen

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (11)XML

Targets (11)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:28 UTC

Update Date

2014-12-24 20:25:52 UTC

Accession Number

T3D2866

Identification

Common Name

Flurbiprofen

Class

Small Molecule

Description

Flurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with antipyretic and analgesic activity. Oral formulations of flurbiprofen may be used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and anklylosing spondylitis. Flurbiprofen may also be used topically prior to ocular surgery to prevent or reduce intraoperative miosis. Flurbiprofen is structurally and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen.

Compound Type

Analgesic
Anti-Inflammatory Agent
Anti-Inflammatory Agent, Non-Steroidal
Carbonic Anhydrase Inhibitor
Cyclooxygenase Inhibitor
Drug
Metabolite
Organic Compound
Organofluoride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(+-)-2-Fluoro-alpha-methyl-4-biphenylacetic acid
2-(2-Fluorobiphenyl-4-yl)propanoic acid
2-Fluoro-alpha-methyl-(1,1'-biphenyl)-4-acetic acid
3-Fluoro-4-phenylhydratropic acid
Acustop Cataplasma
Adofeed
Ansaid
Antadys
Cebutid
FLP
Flurbiprofene
Flurbiprofeno
Flurbiprofenum
Flurofen
Froben
Froben Sr
Ocufen
Ocuflur
S-flurbiprofen
Stayban
Strefen
Strepfen
Strepsils
Strepsils Intensive
TransAct
Urbifen
Zepolas

Chemical Formula

C₁₅H₁₃FO₂

Average Molecular Mass

244.261 g/mol

Monoisotopic Mass

244.090 g/mol

CAS Registry Number

5104-49-4

IUPAC Name

2-{2-fluoro-[1,1'-biphenyl]-4-yl}propanoic acid

Traditional Name

flurbiprofen

SMILES

CC(C(O)=O)C1=CC(F)=C(C=C1)C1=CC=CC=C1

InChI Identifier

InChI=1/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)

InChI Key

InChIKey=SYTBZMRGLBWNTM-UHFFFAOYNA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Biphenyls and derivatives

Direct Parent

Biphenyls and derivatives

Alternative Parents

Substituents

Biphenyl
2-phenylpropanoic-acid
P-cymene
Aromatic monoterpenoid
Monocyclic monoterpenoid
Monoterpenoid
Fluorobenzene
Halobenzene
Aryl halide
Aryl fluoride
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organooxygen compound
Organic oxygen compound
Carbonyl group
Hydrocarbon derivative
Organic oxide
Organofluoride
Organohalogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

fluorobiphenyl (CHEBI:5130 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

non-narcotic analgesic

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	110-111°C
Boiling Point	Not Available
Solubility	8 mg/L (at 22°C)
LogP	4.16

Predicted Properties

Property	Value	Source
Water Solubility	0.025 g/L	ALOGPS
logP	3.57	ALOGPS
logP	3.94	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	4.42	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	3	ChemAxon
Refractivity	67.29 m³·mol⁻¹	ChemAxon
Polarizability	25.23 Å³	ChemAxon
Number of Rings	2	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
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0002-2940000000-9f5fff7c7dd3930840ab	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0fft-9531000000-d8e1afedb8496d7ccae1	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
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 - LC-ESI-qTof , Positive	splash10-002b-0900000000-1c9889f5fc33443c7b3b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-002b-0900000000-1791423706be24cc354b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0229-3920000000-b822873abe0cc77b6500	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-002b-0900000000-1791423706be24cc354b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-002b-0900000000-1c9889f5fc33443c7b3b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-004i-2900000000-d74a9b309815da3ba05d	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0002-0900000000-be4ed0fe252134b8d5d0	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0290000000-a84327eef03dc68e08c6	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0890000000-8fb4c7dcd6ef32ab325b	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00ba-2910000000-570b59a950d65dd4631e	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0390000000-68c52b6d3396c526a75c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0005-1950000000-7014af9c0d6f2fc23c18	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00fr-5910000000-9a60410e16b662ddcff0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0090000000-cbd4141a005693f2c6aa	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0940000000-f30f7aa21a68a7f1ab95	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-004i-0900000000-2bf6ee99259baef46083	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-002b-0910000000-b3fba75f1be1c305f3d6	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0900000000-f48dedd82d182cffdfbf	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0fi0-0900000000-150de333ffe505b0359d	2021-10-11	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, 100.54 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Fluribiprofen is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations are reached 0.5 - 4 hours after oral administration.

Mechanism of Toxicity

Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.

Metabolism

Hepatic. Cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. Route of Elimination: Flurbiprofen is poorly excreted into human milk. Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination of flurbiprofen metabolites. Half Life: R-flurbiprofen, 4.7 hours; S-flurbiprofen, 5.7 hours

Toxicity Values

LD50: 10 mg/kg (Oral, Dog) (2)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

Flurbiprofen tablets are indicated for the acute or long-term symptomatic treatment of rheumatoid arthritis, osteorarthritis and anklosing spondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic formulations may be used pre-operatively to prevent intraoperative miosis.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Symptoms of a flurbiprofen overdose may include nausea, vomiting, stomach pain, dizziness, drowsiness, black or bloody stools, coughing up blood, urinating less than usual or not at all, shallow breathing, fainting, or coma.

Treatment

Patients should be managed by symptomatic and supportive care following overdose with a nonsteroidal anti-inflammatory drug. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms, or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. (8)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

5130

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Flurbiprofen

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Flurbiprofen

References

Synthesis Reference

Yutaka Mizushima, Hiroyuki Okamoto, Shigetoshi Sugio, Kazumasa Yokoyama, Tadakazu Suyama, Masao Tohno, Makoto Okumura, Yoshiaki Konishi, Kiyonoshin Ichikawa, Katsuhiro Uchida, “Flurbiprofen derivative ophthalmic preparation.” U.S. Patent US5171566, issued January, 1984.

MSDS

Link

General References

Needleman HL, Schell A, Bellinger D, Leviton A, Allred EN: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med. 1990 Jan 11;322(2):83-8. [2294437 ]
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 ]
Geerts H: Drug evaluation: (R)-flurbiprofen--an enantiomer of flurbiprofen for the treatment of Alzheimer's disease. IDrugs. 2007 Feb;10(2):121-33. [17285465 ]
Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [19515014 ]
Calapai G, Imbesi S, Cafeo V, Ventura Spagnolo E, Minciullo PL, Caputi AP, Gangemi S, Milone L: Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report. J Clin Pharm Ther. 2013 Aug;38(4):337-8. doi: 10.1111/jcpt.12073. Epub 2013 May 13. [23668805 ]
Mironov GG, Logie J, Okhonin V, Renaud JB, Mayer PM, Berezovski MV: Comparative study of three methods for affinity measurements: capillary electrophoresis coupled with UV detection and mass spectrometry, and direct infusion mass spectrometry. J Am Soc Mass Spectrom. 2012 Jul;23(7):1232-40. doi: 10.1007/s13361-012-0386-y. Epub 2012 Apr 28. [22544663 ]
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	4.23 uM	Not Available	BindingDB 50074922
IC50	0.01 uM	Not Available	BindingDB 50074922
IC50	0.91 uM	Not Available	BindingDB 50172479

References

Bayly CI, Black WC, Leger S, Ouimet N, Ouellet M, Percival MD: Structure-based design of COX-2 selectivity into flurbiprofen. Bioorg Med Chem Lett. 1999 Feb 8;9(3):307-12. [10091674 ]
Kusuhara H, Komatsu H, Sumichika H, Sugahara K: Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells. Eur J Pharmacol. 1999 Nov 3;383(3):331-7. [10594327 ]
van Haeringen NJ, van Sorge AA, Carballosa Core-Bodelier VM: Constitutive cyclooxygenase-1 and induced cyclooxygenase-2 in isolated human iris inhibited by S(+) flurbiprofen. J Ocul Pharmacol Ther. 2000 Aug;16(4):353-61. [10977131 ]
Smith T, McCracken J, Shin YK, DeWitt D: Arachidonic acid and nonsteroidal anti-inflammatory drugs induce conformational changes in the human prostaglandin endoperoxide H2 synthase-2 (cyclooxygenase-2). J Biol Chem. 2000 Dec 22;275(51):40407-15. [11006278 ]
Hinz B, Brune K, Rau T, Pahl A: Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages. Pharm Res. 2001 Feb;18(2):151-6. [11405284 ]
Needleman HL, Schell A, Bellinger D, Leviton A, Allred EN: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med. 1990 Jan 11;322(2):83-8. [2294437 ]
Blobaum AL, Marnett LJ: Structural and functional basis of cyclooxygenase inhibition. J Med Chem. 2007 Apr 5;50(7):1425-41. Epub 2007 Mar 7. [17341061 ]
Peretto I, Radaelli S, Parini C, Zandi M, Raveglia LF, Dondio G, Fontanella L, Misiano P, Bigogno C, Rizzi A, Riccardi B, Biscaioli M, Marchetti S, Puccini P, Catinella S, Rondelli I, Cenacchi V, Bolzoni PT, Caruso P, Villetti G, Facchinetti F, Del Giudice E, Moretto N, Imbimbo BP: Synthesis and biological activity of flurbiprofen analogues as selective inhibitors of beta-amyloid(1)(-)(42) secretion. J Med Chem. 2005 Sep 8;48(18):5705-20. [16134939 ]
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 ]

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

References

Rieke CJ, Mulichak AM, Garavito RM, Smith WL: The role of arginine 120 of human prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors. J Biol Chem. 1999 Jun 11;274(24):17109-14. [10358065 ]
Hewett SJ, Uliasz TF, Vidwans AS, Hewett JA: Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture. J Pharmacol Exp Ther. 2000 May;293(2):417-25. [10773011 ]
Kurahashi K, Shirahase H, Nakamura S, Tarumi T, Koshino Y, Wang AM, Nishihashi T, Shimizu Y: Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites. J Cardiovasc Pharmacol. 2001 Oct;38 Suppl 1:S21-5. [11811354 ]
Klegeris A, McGeer PL: Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity. Neurobiol Aging. 2002 Sep-Oct;23(5):787-94. [12392782 ]
Droge MJ, van Sorge AA, van Haeringen NJ, Quax WJ, Zaagsma J: Alternative splicing of cyclooxygenase-1 mRNA in the human iris. Ophthalmic Res. 2003 May-Jun;35(3):160-3. [12711844 ]
Needleman HL, Schell A, Bellinger D, Leviton A, Allred EN: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med. 1990 Jan 11;322(2):83-8. [2294437 ]

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

Evans SM, Whittle BJ: Interactive roles of superoxide and inducible nitric oxide synthase in rat intestinal injury provoked by non-steroidal anti-inflammatory drugs. Eur J Pharmacol. 2001 Oct 19;429(1-3):287-96. [11698048 ]
Takla PG, Schulman SG, Perrin JH: Measurement of flurbiprofen-human serum albumin interaction by fluorimetry. J Pharm Biomed Anal. 1985;3(1):41-50. [16867708 ]
Gudgeon JR, Martin W: Modulation of arterial endothelial permeability: studies on an in vitro model. Br J Pharmacol. 1989 Dec;98(4):1267-74. [2514947 ]
Aarons L, Khan AZ, Grennan DM, Alam-Siddiqi M: The binding of flurbiprofen to plasma proteins. J Pharm Pharmacol. 1985 Sep;37(9):644-6. [2867185 ]
Castell JV, Larrauri A, Gomez-Lechon MJ: A study of the relative hepatotoxicity in vitro of the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen and butibufen. Xenobiotica. 1988 Jun;18(6):737-45. [3420949 ]
Needleman HL, Schell A, Bellinger D, Leviton A, Allred EN: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med. 1990 Jan 11;322(2):83-8. [2294437 ]

Target Details

4. Aldo-keto reductase family 1 member C1

General Function:: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function:: Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
Gene Name:: AKR1C1
Uniprot ID:: Q04828
Molecular Weight:: 36788.02 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>100 uM	Not Available	BindingDB 50074922

References

Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA: 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem. 2012 Sep 13;55(17):7746-58. doi: 10.1021/jm3007867. Epub 2012 Aug 21. [22877157 ]

Target Details

5. Aldo-keto reductase family 1 member C2

General Function:: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function:: Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
Gene Name:: AKR1C2
Uniprot ID:: P52895
Molecular Weight:: 36734.97 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	32.5 uM	Not Available	BindingDB 50074922

References

Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA: 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem. 2012 Sep 13;55(17):7746-58. doi: 10.1021/jm3007867. Epub 2012 Aug 21. [22877157 ]

Target Details

6. 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	1.56 uM	Not Available	BindingDB 50074922

References

Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA: 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem. 2012 Sep 13;55(17):7746-58. doi: 10.1021/jm3007867. Epub 2012 Aug 21. [22877157 ]

Target Details

7. Aldo-keto reductase family 1 member C4

General Function:: Retinal dehydrogenase activity
Specific Function:: Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route.
Gene Name:: AKR1C4
Uniprot ID:: P17516
Molecular Weight:: 37066.52 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>100 uM	Not Available	BindingDB 50074922

References

Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA: 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem. 2012 Sep 13;55(17):7746-58. doi: 10.1021/jm3007867. Epub 2012 Aug 21. [22877157 ]

Target Details

8. 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

References

Shimada T, Tanaka K, Takenaka S, Murayama N, Martin MV, Foroozesh MK, Yamazaki H, Guengerich FP, Komori M: Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives. Chem Res Toxicol. 2010 Dec 20;23(12):1921-35. doi: 10.1021/tx100286d. [21053930 ]

Target Details

9. Fas-binding factor 1

General Function:: Not Available
Specific Function:: Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:: FBF1
Uniprot ID:: Q8TES7
Molecular Weight:: 125445.19 Da

References

Borga O, Borga B: Serum protein binding of nonsteroidal antiinflammatory drugs: a comparative study. J Pharmacokinet Biopharm. 1997 Feb;25(1):63-77. [9353694 ]

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	26 uM	Not Available	BindingDB 50074922

References

Chuang S, Velkov T, Horne J, Porter CJ, Scanlon MJ: Characterization of the drug binding specificity of rat liver fatty acid binding protein. J Med Chem. 2008 Jul 10;51(13):3755-64. doi: 10.1021/jm701192w. Epub 2008 Jun 6. [18533710 ]

Target Details

11. 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	1.5 uM	Not Available	BindingDB 50074922

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 ]

Flurbiprofen (T3D2866)

Structure for T3D2866: Flurbiprofen

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