Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEH0J8X)

DME Name Arachidonate 15-lipoxygenase (ALOX15)
Synonyms Arachidonate 12-lipoxygenase leukocyte-type; Arachidonate omega-6 lipoxygenase; LOG15; 12-LOX; 12/15-lipoxygenase; 15-LOX; 15-LOX-1; ALOX15
Gene Name ALOX15
UniProt ID
LOX15_HUMAN
INTEDE ID
DME0403
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
246
EC Number EC: 1.13.11.33
Oxidoreductase
Oxygen single donor oxidoreductase
Oxygen single donor oxidoreductase
EC: 1.13.11.33
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP
QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK
GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV
LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL
VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH
LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST
GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS
LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH
ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ
PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV
AI
Function
This enzyme catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. It converts arachidonic acid into 12-hydroperoxyeicosatetraenoic acid/12- HPETE and 15-hydroperoxyeicosatetraenoic acid/15-HPETE. It also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid and may also act on (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3.
KEGG Pathway
Arachidonic acid metabolism (hsa00590 )
Ferroptosis (hsa04216 )
Linoleic acid metabolism (hsa00591 )
Metabolic pathways (hsa01100 )
Necroptosis (hsa04217 )
Serotonergic synapse (hsa04726 )
Reactome Pathway
Biosynthesis of DPAn-3-derived protectins and resolvins (R-HSA-9026286 )
Biosynthesis of DPAn-6 SPMs (R-HSA-9025106 )
Biosynthesis of E-series 18(R)-resolvins (R-HSA-9023661 )
Biosynthesis of E-series 18(S)-resolvins (R-HSA-9018896 )
Biosynthesis of protectins (R-HSA-9018681 )
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )
Synthesis of 12-eicosatetraenoic acid derivatives (R-HSA-2142712 )
Synthesis of 15-eicosatetraenoic acid derivatives (R-HSA-2142770 )
Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691 )
Biosynthesis of DHA-derived SPMs (R-HSA-9018677 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Arachidonic acid DMUOQZD Discovery agent N.A. Investigative [9]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 8.36E-09 -1.60E-01 -5.39E-01
Alopecia ED70 Skin from scalp 3.32E-06 3.59E-01 8.37E-01
Alzheimer's disease 8A20 Entorhinal cortex 4.61E-01 -2.18E-02 -1.44E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 6.59E-02 4.55E-02 4.76E-01
Aortic stenosis BB70 Calcified aortic valve 7.78E-02 -1.01E-01 -4.34E-01
Apnea 7A40 Hyperplastic tonsil 5.83E-01 -2.59E-02 -2.28E-01
Arthropathy FA00-FA5Z Peripheral blood 6.02E-01 2.28E-01 4.09E-01
Asthma CA23 Nasal and bronchial airway 3.86E-02 2.25E-01 4.01E-01
Atopic dermatitis EA80 Skin 1.27E-03 2.80E-01 1.38E+00
Autism 6A02 Whole blood 9.44E-01 -1.19E-01 -2.85E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.51E-02 -5.17E-02 -3.96E-01
Autosomal dominant monocytopenia 4B04 Whole blood 6.66E-01 -1.30E-01 -1.18E-01
Bacterial infection of gingival 1C1H Gingival tissue 8.42E-02 1.54E-02 1.36E-01
Batten disease 5C56.1 Whole blood 5.09E-01 -3.48E-02 -5.39E-01
Behcet's disease 4A62 Peripheral blood 2.24E-01 -9.27E-02 -4.76E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 6.82E-01 -3.86E-02 -2.01E-01
Bladder cancer 2C94 Bladder tissue 1.69E-01 4.09E-02 2.75E-01
Breast cancer 2C60-2C6Z Breast tissue 4.05E-01 -1.46E-02 -6.94E-02
Cardioembolic stroke 8B11.20 Whole blood 1.95E-05 -1.38E+00 -1.44E+00
Cervical cancer 2C77 Cervical tissue 3.94E-01 -5.99E-02 -3.29E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 7.64E-01 3.38E-02 2.04E-02
Chronic hepatitis C 1E51.1 Whole blood 6.96E-01 -2.23E-03 -2.47E-02
Chronic obstructive pulmonary disease CA22 Lung tissue 4.54E-01 -5.26E-02 -1.39E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.66E-03 -3.11E-01 -5.13E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 7.12E-02 -1.18E+00 -9.40E-01
Colon cancer 2B90 Colon tissue 1.21E-06 -1.76E-01 -5.88E-01
Coronary artery disease BA80-BA8Z Peripheral blood 8.35E-01 8.43E-02 3.16E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 5.19E-01 8.44E-02 9.75E-01
Endometriosis GA10 Endometrium tissue 8.52E-01 -1.97E-02 -1.21E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 8.56E-01 -4.18E-02 -4.50E-01
Familial hypercholesterolemia 5C80.00 Whole blood 7.89E-05 -3.61E-01 -9.12E-01
Gastric cancer 2B72 Gastric tissue 3.82E-01 -2.75E-01 -7.54E-01
Glioblastopma 2A00.00 Nervous tissue 3.47E-56 -2.30E-01 -1.00E+00
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 4.93E-01 1.30E-01 7.60E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 2.38E-01 2.54E-03 1.89E-02
Head and neck cancer 2D42 Head and neck tissue 3.00E-12 -2.62E-01 -8.95E-02
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 2.49E-01 -6.99E-02 -2.30E-01
Huntington's disease 8A01.10 Whole blood 2.91E-01 -3.37E-02 -1.62E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 3.40E-03 7.97E-01 3.17E+00
Immunodeficiency 4A00-4A20 Peripheral blood 6.08E-01 -5.41E-02 -6.21E-01
Influenza 1E30 Whole blood 7.76E-03 5.39E-01 5.14E+00
Interstitial cystitis GC00.3 Bladder tissue 4.46E-01 4.94E-02 2.82E-01
Intracranial aneurysm 8B01.0 Intracranial artery 6.51E-01 -3.58E-02 -1.83E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 5.29E-01 2.54E-02 1.18E-01
Ischemic stroke 8B11 Peripheral blood 9.25E-01 -5.90E-02 -4.13E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 1.77E-03 7.62E-02 5.21E-02
Lateral sclerosis 8B60.4 Skin 1.60E-01 -6.52E-02 -6.59E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 9.03E-02 4.80E-01 1.49E+00
Liver cancer 2C12.0 Liver tissue 6.34E-03 -1.05E-01 -5.20E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.74E-02 -2.42E-01 -1.01E+00
Lung cancer 2C25 Lung tissue 1.84E-06 -2.96E-01 -3.53E-01
Lupus erythematosus 4A40 Whole blood 3.09E-01 -1.71E-01 -2.01E-01
Major depressive disorder 6A70-6A7Z Hippocampus 5.77E-01 -5.28E-02 -3.38E-01
Major depressive disorder 6A70-6A7Z Whole blood 1.60E-01 2.55E-01 2.20E-01
Melanoma 2C30 Skin 1.37E-02 -3.04E-01 -8.75E-01
Multiple myeloma 2A83.1 Peripheral blood 7.95E-01 7.76E-03 7.12E-02
Multiple myeloma 2A83.1 Bone marrow 2.05E-01 -1.74E-02 -1.71E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 2.00E-01 -1.35E-01 -4.57E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 3.39E-01 9.39E-03 9.45E-02
Myelofibrosis 2A20.2 Whole blood 5.16E-02 2.45E-01 4.87E-01
Myocardial infarction BA41-BA50 Peripheral blood 2.36E-01 9.30E-02 2.16E-01
Myopathy 8C70.6 Muscle tissue 2.23E-01 -6.83E-02 -2.05E-01
Neonatal sepsis KA60 Whole blood 1.01E-08 -2.21E-01 -5.67E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 3.72E-03 -2.73E-01 -1.20E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 3.17E-01 -4.65E-02 -7.38E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 6.10E-04 -1.21E+00 -2.96E+00
Olive pollen allergy CA08.00 Peripheral blood 6.23E-01 -8.05E-03 -3.61E-02
Oral cancer 2B6E Oral tissue 2.11E-03 -1.92E-01 -6.35E-01
Osteoarthritis FA00-FA0Z Synovial tissue 3.74E-01 -1.03E-01 -6.04E-01
Osteoporosis FB83.1 Bone marrow 9.50E-01 4.18E-02 2.36E-01
Ovarian cancer 2C73 Ovarian tissue 5.78E-01 -2.43E-02 -2.12E-01
Pancreatic cancer 2C10 Pancreas 2.39E-02 -1.84E-01 -8.18E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 7.49E-01 2.39E-03 1.23E-02
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 4.87E-01 -5.77E-02 -3.30E-01
Pituitary cancer 2D12 Pituitary tissue 9.73E-01 -7.72E-02 -3.19E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 9.70E-01 3.54E-03 2.42E-02
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 8.08E-01 4.80E-04 3.26E-03
Polycythemia vera 2A20.4 Whole blood 2.72E-01 1.78E-01 3.50E-01
Pompe disease 5C51.3 Biceps muscle 1.38E-01 -1.61E-02 -7.16E-02
Preterm birth KA21.4Z Myometrium 1.76E-01 -1.36E-01 -1.15E+00
Prostate cancer 2C82 Prostate 3.91E-03 7.71E-02 1.38E-01
Psoriasis EA90 Skin 8.84E-01 -1.80E-03 -5.66E-03
Rectal cancer 2B92 Rectal colon tissue 6.24E-01 -1.38E-01 -6.26E-01
Renal cancer 2C90-2C91 Kidney 7.81E-03 -2.27E-01 -5.32E-01
Retinoblastoma 2D02.2 Uvea 2.38E-01 -1.42E-01 -2.14E+00
Rheumatoid arthritis FA20 Synovial tissue 1.23E-02 -6.43E-01 -1.57E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 8.22E-01 8.69E-02 3.59E-01
Schizophrenia 6A20 Prefrontal cortex 3.14E-01 -2.17E-02 -1.08E-01
Schizophrenia 6A20 Superior temporal cortex 4.93E-01 -3.90E-03 -3.63E-02
Scleroderma 4A42.Z Whole blood 3.11E-01 1.10E-01 3.35E-01
Seizure 8A60-8A6Z Whole blood 9.65E-01 2.12E-01 4.25E-01
Sensitive skin EK0Z Skin 6.90E-01 -2.02E-01 -5.34E-01
Sepsis with septic shock 1G41 Whole blood 2.01E-20 -2.34E-01 -6.23E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 2.39E-01 -1.09E-01 -9.77E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 7.08E-01 8.83E-02 2.05E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 8.17E-01 2.10E-02 1.35E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 4.16E-01 -9.59E-03 -1.69E-01
Skin cancer 2C30-2C3Z Skin 4.06E-08 -1.52E-01 -3.72E-01
Thrombocythemia 3B63 Whole blood 1.98E-01 8.27E-02 1.73E-01
Thrombocytopenia 3B64 Whole blood 3.89E-01 4.96E-02 3.08E-01
Thyroid cancer 2D10 Thyroid 8.69E-02 4.18E-02 2.16E-01
Tibial muscular dystrophy 8C75 Muscle tissue 1.96E-02 -2.25E-01 -7.52E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 1.48E-01 1.14E-01 1.64E+00
Type 2 diabetes 5A11 Liver tissue 6.68E-01 -3.08E-02 -5.48E-01
Ureter cancer 2C92 Urothelium 7.70E-01 7.90E-02 2.85E-01
Uterine cancer 2C78 Endometrium tissue 7.10E-03 -1.20E-04 -4.71E-04
Vitiligo ED63.0 Skin 3.00E-01 3.69E-01 9.12E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Arachidonate 15-lipoxygenase (15-LOX) DTT Info
DME DTT Type Patented-recorded
8 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Imidazole derivative 10 DMI7W3K N. A. N. A. Patented [1]
Imidazole derivative 11 DMTJ0DP N. A. N. A. Patented [1]
Indole and benzimidazole derivative 1 DMS0169 N. A. N. A. Patented [1]
Indolizine derivative 1 DM4GZBI N. A. N. A. Patented [2]
Isothiazolone derivative 1 DMHAJCM N. A. N. A. Patented [1]
PMID26560362-Compound-90 DM9V13U N. A. N. A. Patented [1]
Tri-substituted benzene derivative 1 DMEQ3RD N. A. N. A. Patented [1]
Triazole derivative 3 DMZR0TH N. A. N. A. Patented [1]
⏷ Show the Full List of 8 Patented Agent(s)
1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
NSC-661755 DMDJT7U N. A. N. A. Terminated [3]
30 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(+)-(5S,8S,10S)-20-methoxy-9,15-ene-puupehenol DMLDQWT Discovery agent N.A. Investigative [4]
(+)-(5S,8S,10S)-20-methoxypuupehenol DMU7BJA Discovery agent N.A. Investigative [4]
(+)-(5S,8S,9R,10S)-20-methoxypuupehenone DMD4YPO Discovery agent N.A. Investigative [4]
(+)-3,3'-bisdemethyltanegool DMNUWVB Discovery agent N.A. Investigative [5]
(-)-3,3'-bisdemethylpinoresinol DMGC7F5 Discovery agent N.A. Investigative [5]
(-)-pinoresinol DM4INSG Discovery agent N.A. Investigative [5]
(2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID DMKWRFA Discovery agent N.A. Investigative [6]
2,3,4,5-Tetrabromo-6-(2,4-dibromo-phenoxy)-phenol DMK4LTB Discovery agent N.A. Investigative [7]
3,4,6-Tribromo-2-(2,4-dibromo-phenoxy)-phenol DMO34LJ Discovery agent N.A. Investigative [7]
3,4-Dibromo-2-(5-bromo-2-hydroxy-phenoxy)-phenol DMXQVRD Discovery agent N.A. Investigative [7]
3,6,8-Tribromo-dibenzo[1,4]dioxin-1-ol DMM632N Discovery agent N.A. Investigative [7]
CHLOROPUUPEHENONE DM8B0VZ Discovery agent N.A. Investigative [4]
Dimethylnordihydroguarierate acid DMG3WTE Discovery agent N.A. Investigative [4]
DYSIDENIN DMIZQTX Discovery agent N.A. Investigative [3]
Halisulfate 1 DMJB87Q Discovery agent N.A. Investigative [4]
Hydrohalisulfate 1 DM0HQF6 Discovery agent N.A. Investigative [4]
IGERNELLIN DMFMY1L Discovery agent N.A. Investigative [4]
Isojaspic acid DMHTBDN Discovery agent N.A. Investigative [8]
ISOSCOPOLETIN DMNM2SQ Discovery agent N.A. Investigative [5]
JASPAQUINOL DMJAEMT Discovery agent N.A. Investigative [8]
Jaspic acid DMOF0TB Discovery agent N.A. Investigative [4]
Kaempferol DMHEMUB Discovery agent N.A. Investigative [5]
MANGOSTIN DMYQGDV Discovery agent N.A. Investigative [3]
NSC-172033 DM9QW8N Discovery agent N.A. Investigative [3]
Polybrominated diphenyl ether derivative DMG7K84 Discovery agent N.A. Investigative [7]
PUUPEHEDIONE DMF28IU Discovery agent N.A. Investigative [8]
PUUPEHENONE DMF3BCK Discovery agent N.A. Investigative [8]
SCOPOLETIN DM645FP Discovery agent N.A. Investigative [5]
SPONGIADIOXIN A DM0GJVS Discovery agent N.A. Investigative [7]
Subersic acid DM8BLXT Discovery agent N.A. Investigative [4]
⏷ Show the Full List of 30 Investigative Drug(s)

References

1 15-Lipoxygenase inhibitors: a patent review.Expert Opin Ther Pat. 2016;26(1):65-88.
2 Inhibitors of phospholipase A2 and their therapeutic potential: an update on patents (2012-2016).Expert Opin Ther Pat. 2017 Feb;27(2):217-225.
3 Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries. Bioorg Med Chem. 2007 Nov 15;15(22):6900-8.
4 Exploring sponge-derived terpenoids for their potency and selectivity against 12-human, 15-human, and 15-soybean lipoxygenases. J Nat Prod. 2003 Feb;66(2):230-5.
5 Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti. J Nat Prod. 2007 May;70(5):859-62.
6 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
7 Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase. J Med Chem. 2004 Jul 29;47(16):4060-5.
8 Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J Nat Prod. 2009 Oct;72(10):1857-63.
9 Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts. Prostaglandins Other Lipid Mediat. 2013 Oct;106:8-15.