Therapeutic Targets Database
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TTD Target ID: TTDS00112

Target Information
NameArachidonate 5-lipoxygenase    
Type of targetSuccessful target    
Synonyms5-LO    
5-LOX    
5-lipoxygenase    
DiseaseAdult respiratory distress syndrome
[ICD9: 518.5, 518.82   ICD10: J80]
[1]
Allergic diseases
[ICD9: 995.3   ICD10: T78.4]
[2]
Allergic rhinitis, unspecified
[ICD9: 472.0, 477, 995.3   ICD10: J00, J30, J31.0, T78.4]
[3]
Antigen-induced decrease in coronary flow and cardiac anaphylaxis
[ICD9: 995.0   ICD10: T78.2]
[4]
Asthma
[ICD9: 493   ICD10: J45]
[5]
Bronchiolar carcinoma
[ICD9: 162   ICD10: C34]
[6]
Cerebral vasospasm
[ICD9: 443.9   ICD10: I73.9]
[7]
Cervical cancer
[ICD9: 180   ICD10: C53]
[8]
Chronic myeloid leukemia
[ICD9: 205.1   ICD10: C92.1]
[9]
Dermatological disorders[10]
Gastrointestinal cancers
[ICD9: 150-159   ICD10: C15-C26]
[11]
Glomerulonephritis
[ICD9: 580-582   ICD10: N00, N01, N03, N18]
[12]
Inflammatory bowel disease
[ICD9: 555, 556   ICD10: K50, K51]
[13]
Inflammatory lung disease[13]
Magnesium deficiency dermatitis
[ICD9: 692.9   ICD10: L20-L30]
[14]
Nephrosis[15]
Osteoarthritis
[ICD9: 715   ICD10: M15-M19, M47]
[16]
Pancreatic cancer
[ICD9: 157   ICD10: C25]
[17]
Polyarthritis, unspecified[18]
Prion diseases[19]
Psoriasis
[ICD9: 696   ICD10: L40]
[20]
Pulmonary fibrosis
[ICD9: 515, 516.3   ICD10: J84.1]
[21]
Sjogren-Larsson syndrome
[ICD9: 757.1   ICD10: Q87.1]
[22]
Ulcerative colitis
[ICD9: 556   ICD10: K51]
[23]
Urological cancers
[ICD9: 140-229   ICD10: C00-C96]
[24]
Vasospasm[25]
Drug(s)DiethylcarbamazineApprovedLymphatic filariasis[26]
MasoprocolApprovedProstate cancer[27]
ZileutonApprovedAsthma[28][29][30][31][5][10]
LicofelonePhase IIIOsteoarthritis[32][33][34][16]
LinazolastPhase IIIInflammatory Disorders[10][3]
LinetastinePhase IIIInflammatory disease[10][3]
Leukotriene antagonistPhase IIIdiopathic pulmonary fibrosis[35]
ABT-761Discontinued in Phase IIIAsthma[7][36]
CJ-13610Discontinued in Phase IIAsthma[37]
LonapaleneDiscotinued in Phase IIIPsoriasis[10][38]
MK-591Discontinued in Phase IIUlcerative Colitis[39][40]
BioChemical ClassOxidoreductases acting on single donors    
EC NumberEC 1.13.11.34
PathwayArachidonic acid metabolism
Linoleic acid metabolism
Metabolic pathways
UniProt IDP09917
PDB Structure2ABV; 3O8Y; 3V92; 3V98; 3V99.    
SequenceMPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDE ELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLA RDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNG CNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDP CTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECG LFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWE AIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYL TVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCW HLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPY YYLSPDRIPNSVAI
Related US Patent6,344,563
6,346,624
6,432,999
6,455,541
6,479,546
6,512,121
6,515,014
6,677,364
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
InhibitorA-78773[41]
A-79175[42][43]
AA-861[44][45][25][4]
ABT-761[7][36]
ACACETIN[46]
ANTHRONE[47]
Acanthus ilicifolius Linn[48]
Azelastine hydrochloride[14]
BAICALEIN[49]
BUDDLEDIN A[46]
BW A360C[50]
BW A4C[51][52][50][52]
BW B218C[50]
BW B70C[50]
BW-755C[53]
BW755C[48]
CGS 8515[54]
CJ-13610[37]
CV-6504[17][15]
CV-6504 HCl[15]
CYLINDOL A[55]
Caffeic acid[56][57][19]
Chebulagic acid[58]
Diethylcarbamazine[26]
ETH615[10]
Fuscoside[13]
Heme[59]
Hyperforin[2]
ICI 207968[52]
Ibuproxam[60]
JUGLONE[47]
L-652,343[18]
Leukotriene antagonist[35]
Licofelone[32][33][34][16]
Linazolast[10][3]
Linetastine[10][3]
Lonapalene[10][38]
MK-591[39][40]
MK-886[61][6][10]
Masoprocol[27]
NAFAZATROM[53]
NAPHTHAZALIN[47]
Nordihydroguaiaretic acid[62]
PHENIDONE[55]
PYROGALLOL[47]
Quinacrine HCl[19]
Quinacrine azide[19]
Quinacrine dihydrochloride[19]
R-68151[10][20]
R-85355[20]
REV-5901[49]
SB 202235[63]
SC41661A[9]
SK&F 107649[12]
SK&F 86002[1]
Silymarin[64]
TEBUFELONE[65]
TZI-41127[66]
Tepoxalin[67]
ZM-211965[46]
ZM-230487[68]
Zileuton[28][29][30][31][5][10]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Therapeutic intervention in a rat model of ARDS: I. Dual inhibition of arachidonic acid metabolism. Circ Shock. 1990 Nov;32(3):231-42. To Reference
Ref 2Biochem Pharmacol. 2002 Dec 15;64(12):1767-75.Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. To Reference
Ref 3Effects of TMK688, a novel anti-allergic drug, on allergic nasal obstruction and exudative responses in sensitized guinea pigs. Naunyn Schmiedebergs Arch Pharmacol. 1997 Dec;356(6):815-9. To Reference
Ref 4Characterization and modulation of antigen-induced effects in isolated rat heart. J Cardiovasc Pharmacol. 1991 Oct;18(4):556-65. To Reference
Ref 5Leukotrienes in respiratory disease. Paediatr Respir Rev. 2001 Sep;2(3):238-44. To Reference
Ref 6A genomic response of H-358 bronchiolar carcinoma cells to MK 886, an inhibitor of 5-lipoxygenase, assessed with a cDNA array. Anticancer Res. 2000 Jul-Aug;20(4):2433-9. To Reference
Ref 7The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage. Neurosurgery. 2001 Nov;49(5):1205-12; discussion 1212-3. To Reference
Ref 8Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells. Br J Cancer. 2002 Apr 8;86(7):1188-96. To Reference
Ref 9Morphologic changes of apoptosis induced in human chronic myelogenous leukemia "blast" cells by SC41661A (Searle), a selective inhibitor of 5-lipoxygenase. Scanning Microsc. 1994;8(3):675-84; discussion 684-6. To Reference
Ref 10Preview of potential therapeutic applications of leukotriene B4 inhibitors in dermatology. Skin Pharmacol Appl Skin Physiol. 2000 Sep-Oct;13(5):235-45. To Reference
Ref 11Eicosanoid production by the human gastric cancer cell line AGS and its relation to cell growth. Cancer Res. 1992 Apr 1;52(7):1744-9. To Reference
Ref 12Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat. Kidney Int. 1994 May;45(5):1301-10. To Reference
Ref 13Fuscoside: an anti-inflammatory marine natural product which selectively inhibits 5-lipoxygenase. Part II: Biochemical studies in the human neutrophil. J Pharmacol Exp Ther. 1992 Aug;262(2):874-82. To Reference
Ref 14Magnesium deficiency dermatitis--changes in leukotriene levels and effects of azelastine hydrochloride on the dermatitis and leukotriene B4. Nippon Hifuka Gakkai Zasshi. 1990 Jun;100(7):757-60. To Reference
Ref 15Involvement of thromboxane A2, leukotrienes and free radicals in puromycin nephrosis in rats. Kidney Int. 1991 May;39(5):920-9. To Reference
Ref 16Licofelone (ML-3000), a dual inhibitor of 5-lipoxygenase and cyclooxygenase, reduces the level of cartilage chondrocyte death in vivo in experimental dog osteoarthritis: inhibition of pro-apoptotic factors. J Rheumatol. 2002 Jul;29(7):1446-53. To Reference
Ref 17A phase II study of the 5-lipoxygenase inhibitor, CV6504, in advanced pancreatic cancer: correlation of clinical data with pharmacokinetic and pharmacodynamic endpoints. Ann Oncol. 2000 Sep;11(9):1165-70. To Reference
Ref 18Pharmacology of the dual inhibitor of cyclooxygenase and 5-lipoxygenase 3-hydroxy-5-trifluoromethyl-N-(2-(2-thienyl)-2-phenyl-ethenyl)-benzo (b)thiophene-2-carboxamide. Arzneimittelforschung. 1988 Mar;38(3):372-8. To Reference
Ref 19Involvement of the 5-lipoxygenase pathway in the neurotoxicity of the prion peptide PrP106-126. J Neurosci Res. 2001 Sep 15;65(6):565-72. To Reference
Ref 20Topical R-85355, a potent and selective 5-lipoxygenase inhibitor, fails to improve psoriasis. Skin Pharmacol. 1996;9(5):307-11. To Reference
Ref 21The 5-lipoxygenase pathway: a new therapeutic target for the treatment of pulmonary fibrosis. Am J Respir Crit Care Med. 2002 Jan 15;165(2):146-7. To Reference
Ref 225-Lipoxygenase inhibition: a new treatment strategy for Sj?gren-Larsson syndrome. Neuropediatrics. 2000 Feb;31(1):1-3. To Reference
Ref 23Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591. Gastroenterology. 1997 Mar;112(3):725-32. To Reference
Ref 24Lipoxygenase inhibitors prevent urological cancer cell growth. Int J Mol Med. 2004 May;13(5):665-8. To Reference
Ref 25Effect of 5-lipoxygenase inhibitor on experimental delayed cerebral vasospasm. Stroke. 1987 Mar-Apr;18(2):512-8. To Reference
Ref 26Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs. Vojnosanit Pregl. 1999 May-Jun;56(3):243-7. To Reference
Ref 27Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL. Am J Physiol Endocrinol Metab. 2000 Sep;279(3):E593-600. To Reference
Ref 285-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Mar 23. [Epub ahead of print] To Reference
Ref 295-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009 Mar;19(3):244-7. To Reference
Ref 30Oxygen-glucose deprivation activates 5-lipoxygenase mediated by oxidative stress through the p38 mitogen-activated protein kinase pathway in PC12 cells. J Neurosci Res. 2009 Mar;87(4):991-1001. To Reference
Ref 31Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model. Clin Cancer Res. 2008 Oct 15;14(20):6525-30. To Reference
Ref 32Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors. Prostaglandins Leukot Essent Fatty Acids. 2008 Feb;78(2):99-108. Epub 2008 Feb 15. To Reference
Ref 33Activity and potential role of licofelone in the management of osteoarthritis. Clin Interv Aging. 2007;2(1):73-9. To Reference
Ref 34Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis. 2008 Feb;29(2):371-80. Epub 2007 Nov 21. To Reference
Ref 35Current and emerging drugs for idiopathic pulmonary fibrosis. Expert Opin Emerg Drugs. 2007 Nov;12(4):627-46. To Reference
Ref 36N-hydroxyurea and hydroxamic acid inhibitors of cyclooxygenase and 5-lipoxygenase. Bioorg Med Chem Lett. 1999 Apr 5;9(7):979-84. To Reference
Ref 37Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. To Reference
Ref 38Pharmacologic and clinical effects of lonapalene (RS 43179), a 5-lipoxygenase inhibitor, in psoriasis. J Invest Dermatol. 1990 Jul;95(1):50-4. To Reference
Ref 39Antileukotriene therapy for asthma. Am J Health Syst Pharm. 1996 Dec 1;53(23):2821-30; quiz 2877-8. To Reference
Ref 40Inhibition of antigen-induced contraction of guinea-pig airways by a leukotriene synthesis inhibitor, BAY x1005. Eur J Pharmacol. 1994 Jun 2;258(1-2):95-102. To Reference
Ref 41J Med Chem. 1998 May 21;41(11):1970-9.(+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N- hydroxyureidyl)methylphenyl]-5-(3,4, 5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a potent dual 5-lipoxygenase inhibitor and platelet-activating factor receptor antagonist. To Reference
Ref 42The role of platelet-activating factor (PAF) and the efficacy of ABT-491, a highly potent and selective PAF antagonist, in experimental allergic rhinitis. J Pharmacol Exp Ther. 1998 Jan;284(1):83-8. To Reference
Ref 43Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773. Ann N Y Acad Sci. 1994 Nov 15;744:262-73. To Reference
Ref 44Platelets stimulate airway smooth muscle cell proliferation through mechanisms involving 5-lipoxygenase and reactive oxygen species. Platelets. 2008 Nov;19(7):528-36. To Reference
Ref 45Leukotriene B4/leukotriene B4 receptor pathway is involved in hepatic microcirculatory dysfunction elicited by endotoxin. Shock. 2008 Jul;30(1):87-91. To Reference
Ref 46J Nat Prod. 1999 Sep;62(9):1241-5.Novel and known constituents from Buddleja species and their activity against leukocyte eicosanoid generation. To Reference
Ref 47J Med Chem. 1997 Nov 7;40(23):3773-80.Simple analogues of anthralin: unusual specificity of structure and antiproliferative activity. To Reference
Ref 48Anti-inflammatory activity of Acanthus ilicifolius. J Ethnopharmacol. 2008 Oct 30;120(1):7-12. Epub 2008 Jul 25. To Reference
Ref 49J Med Chem. 1991 Mar;34(3):1028-36.Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity. To Reference
Ref 50Hydroxamic acids and hydroxyureas as novel, selective 5-lipoxygenase inhibitors for possible use in asthma. Agents Actions Suppl. 1991;34:189-99. To Reference
Ref 51Reactive oxygen species and lipoxygenases regulate the oncogenicity of NPM-ALK-positive anaplastic large cell lymphomas. Oncogene. 2009 Jul 23;28(29):2690-6. Epub 2009 Jun 8. To Reference
Ref 52Tumour necrosis factor production in a rat airpouch model of inflammation: role of eicosanoids. Agents Actions. 1991 Mar;32(3-4):289-94. To Reference
Ref 53J Med Chem. 1990 Apr;33(4):1163-70.Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes. To Reference
Ref 54Characterization of CGS 8515 as a selective 5-lipoxygenase inhibitor using in vitro and in vivo models. Biochim Biophys Acta. 1988 Apr 15;959(3):332-42. To Reference
Ref 55J. Nat. Prod. 57(9):1290-1293 (1994) To Reference
Ref 56Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neurosci Lett. 2008 Nov 7;445(1):1-6. Epub 2008 Aug 22. To Reference
Ref 57Protection of mouse brain from aluminum-induced damage by caffeic acid. CNS Neurosci Ther. 2008 Spring;14(1):10-6. To Reference
Ref 58Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line. J Ethnopharmacol. 2009 Jul 30;124(3):506-12. Epub 2009 May 28. To Reference
Ref 59Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 60J Med Chem. 1987 Nov;30(11):2121-6.In vivo characterization of hydroxamic acid inhibitors of 5-lipoxygenase. To Reference
Ref 615-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J Neurochem. 2008 Feb;104(4):1091-100. Epub 2007 Nov 17. To Reference
Ref 62Cannabidiol-2',6'-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metab Dispos. 2009 Aug;37(8):1733-7. Epub 2009 Apr 30. To Reference
Ref 63Pharmacological characterization of SB 202235, a potent and selective 5-lipoxygenase inhibitor: effects in models of allergic asthma. J Pharmacol Exp Ther. 1995 Jun;273(3):1147-55. To Reference
Ref 64Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000 Mar;7(1):21-4. To Reference
Ref 65J Med Chem. 1998 Mar 26;41(7):1124-37.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. To Reference
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Ref 67Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs. Fundam Appl Toxicol. 1996 Sep;33(1):38-48. To Reference
Ref 68Pharmacological nature of nicotine-induced contraction in the rat basilar artery: involvement of arachidonic acid metabolites. Eur J Pharmacol. 2007 Dec 22;577(1-3):109-14. Epub 2007 Aug 14. To Reference



 

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National University of Singapore, Singapore


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