General Information of the Protein
Protein ID
PT01242
Protein Name
Polyunsaturated fatty acid 5-lipoxygenase
Secondarily
Protein Name
Arachidonate 5-lipoxygenase
Gene Name
ALOX5
Secondarily
Gene Name
LOG5
Sequence
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYYYLSPDRIPNSVAI
    Show/Hide
Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Oxidoreductase
Function
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).
    Show/Hide
Uniprot ID
Primary ID:
P09917

Secondarily ID:
B7ZLS0
E5FPY5
E5FPY7
E5FPY8
Q5JQ14
    Show/Hide
Ensembl ID
ENSG00000012779
HGNC ID
HGNC:435
Subcellular Location
Cytoplasm
Nucleus matrix
Nucleus membrane
Cytoplasm
Perinuclear region
Cytoplasm
Cytosol
Nucleus envelope
Nucleus intermembrane space
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Compound ID Compound Name Compound Formula
CP0423400
(2E,2'E)-(1,1'-(2,2-bis((4-(((E)-3-(3,4-dihydroxyphenyl)acryloyloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)propane-1,3-diyl)bis(1H-1,2,3-triazole-4,1-diyl))bis(methylene) bis(3-(3,4-dihydroxyphenyl)acrylate)
   Show/Hide
C53H48N12O16
 1
1
IC50 = 660 nM
   TI
   LI
   LO
   TS
CP0372402
(E)-2-(4-(cinnamoyloxymethyl)-1H-1,2,3-triazol-1-yl)ethyl 3-(3,4-dihydroxyphenyl)acrylate
   Show/Hide
C23H21N3O6
 1
1
IC50 = 680 nM
   TI
   LI
   LO
   TS
CP0459138
(E)-(1-(2-((E)-3-(3,4-dihydroxyphenyl)acryloyloxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl 3-(3,4-dihydroxyphenyl)acrylate
   Show/Hide
C23H21N3O8
 1
1
IC50 = 740 nM
   TI
   LI
   LO
   TS
CP0372401
(2E,2'E)-(1,1'-(2-((4-(((E)-3-(3,4-dihydroxyphenyl)acryloyloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)propane-1,3-diyl)bis(1H-1,2,3-triazole-4,1-diyl))bis(methylene) bis(3-(3,4-dihydroxyphenyl)acrylate)
   Show/Hide
C41H39N9O13
 1
1
IC50 = 790 nM
   TI
   LI
   LO
   TS
CP0047227
(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid
   Show/Hide
C9H8O4
 1
1
IC50 = 25000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0037113
BW A4C
   Show/Hide
C17H17NO3
 12
1 Activity = 703.067095 nM
2 Activity = 1759.079519 nM
3 Activity = 1868.492571 nM
4 Activity = 4011.929552 nM
5 IC50 = 50 nM
6 IC50 = 60 nM
7 IC50 = 80 nM
8 IC50 = 140 nM
9 IC50 = 160 nM
10 IC50 = 220 nM
11 IC50 = 360 nM
12 IC50 = 3000 nM
CP0063946
CHEBI:4778
   Show/Hide
C17H26O4
 1
1 IC50 = 60 nM
CP0039355
3-(1-(4-chlorobenzyl)-3-(tert-butylthio)-5-isopropyl-1H-indol-2-yl)-2,2-dimethylpropanoic acid
   Show/Hide
C27H34ClNO2S
 2
1 IC50 = 90 nM
2 IC50 > 10 nM
CP0019558
(+-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
   Show/Hide
C11H12N2O2S
 25
1 IC50 = 100 nM
2 IC50 = 150 nM
3 IC50 = 300 nM
4 IC50 = 350 nM
5 IC50 = 410 nM
6 IC50 = 500 nM
7 IC50 = 518 nM
8 IC50 = 540 nM
9 IC50 = 560 nM
10 IC50 = 590 nM
11 IC50 = 600 nM
12 IC50 = 660 nM
13 IC50 = 800 nM
14 IC50 = 1000 nM
15 IC50 = 1100 nM
16 IC50 = 1700 nM
17 IC50 = 1800 nM
18 IC50 = 2000 nM
19 IC50 = 2200 nM
20 IC50 = 3000 nM
21 IC50 = 3300 nM
22 IC50 = 3500 nM
23 IC50 = 3700 nM
24 IC50 = 5300 nM
25 IC50 = 6300 nM
CP0037112
2-({4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl}sulfanyl)octanoic acid
   Show/Hide
C20H26ClN3O2S
 1
1 IC50 = 2000 nM
CP0266724
2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetic acid
   Show/Hide
C24H20ClN3O2S
 1
1 IC50 = 5000 nM
CP0047227
(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid
   Show/Hide
C9H8O4
 2
1 IC50 = 8500 nM
2 IC50 = 16700 nM
CP0124683
(E)-4-(3,5-dimethoxystyryl)phenol
   Show/Hide
C16H16O3
 1
1 IC50 = 9320 nM
Clinical Information about the Protein
Target 1 ( Arachidonate 5-lipoxygenase (5-LOX) )
Target Type Successful Target
Disease 20 Target-related Diseases  20
1 Asthma [ICD-11: CA23]
2 Thrombocytopenia [ICD-11: 3B64]
3 Non-small-cell lung cancer [ICD-11: 2C25.Y]
4 Inflammation [ICD-11: 1A00-CA43.1]
5 Rheumatoid arthritis [ICD-11: FA20]
6 Influenza virus infection [ICD-11: 1E30-1E32]
7 Acromegaly [ICD-11: 5A60.0]
8 Psoriasis vulgaris [ICD-11: EA90]
9 Respiratory disease [ICD-11: CB40]
10 Pruritus [ICD-11: EC90]
11 Thrombosis [ICD-11: DB61-GB90]
12 Dermatitis [ICD-11: EA80-EA89]
13 Chronic obstructive pulmonary disease [ICD-11: CA22]
14 Cardiac disease [ICD-11: BA00-BE2Z]
15 Pain [ICD-11: MG30-MG3Z]
16 Osteoarthritis [ICD-11: FA00-FA05]
17 Allergy [ICD-11: 4A80-4A85]
18 Arthritis [ICD-11: FA20]
19 Arteriosclerosis [ICD-11: BD40]
20 Malaria [ICD-11: 1F40-1F45]
Approved Drug(s) 2 Approved Drugs  2
1 Zileuton Approved
Asthma
2 3,4-Dihydroxycinnamic Acid Phase 4
Thrombocytopenia
Clinical Trial Drug(s) 9 Clinical Trial Drugs  9
1 ABT-761 Phase 3
Asthma
2 Avastin+/-Tarceva Phase 3
Non-small-cell lung cancer
3 FPL-62064 Phase 3
Inflammation
4 Tenidap Phase 3
Rheumatoid arthritis
5 Darbufelone Phase 2/3
Asthma
6 BAICALEIN Phase 2
Influenza virus infection
7 BIM23A760 Phase 2
Acromegaly
8 CMI-392 Phase 2
Psoriasis vulgaris
9 Tepoxalin Phase 2
Asthma
Discontinued Drug(s) 22 Discontinued Drugs  22
1 Ibuproxam Withdrawn from market
Respiratory disease
2 CJ-13610 Discontinued in Phase 2
Asthma
3 DuP-654 Discontinued in Phase 2
Pruritus
4 E-3040 Discontinued in Phase 2
Thrombosis
5 ETH615 Discontinued in Phase 2
Dermatitis
6 MK-591 Discontinued in Phase 2
Asthma
7 MK-886 Discontinued in Phase 2
Asthma
8 MLN-977 Discontinued in Phase 2
Chronic obstructive pulmonary disease
9 OPC-21268 Discontinued in Phase 2
Cardiac disease
10 R-68151 Discontinued in Phase 2
Psoriasis vulgaris
11 TEBUFELONE Discontinued in Phase 2
Pain
12 Licofelone Discontinued in Phase 1
Osteoarthritis
13 A-78773 Terminated
Asthma
14 A-79175 Terminated
Asthma
15 AA-861 Terminated
Allergy
16 BW A4C Terminated
Arthritis
17 BW B70C Terminated
Asthma
18 BW755C Terminated
Inflammation
19 Epocarbazolin-A Terminated
Asthma
20 PD-146176 Terminated
Arteriosclerosis
21 WY-28342 Terminated
Rheumatoid arthritis
22 ZM-230487 Terminated
Asthma
Investigative Drug(s) 1 Investigative Drug  1
1 5,8-Dihydroxy-1,4-naphthoquinone Investigative
Malaria
Target 2 ( LOX-5 messenger RNA (ALOX5 mRNA) )
Target Type Discontinued Target
Disease 3 Target-related Diseases  3
1 Pain [ICD-11: MG30-MG3Z]
2 Asthma [ICD-11: CA23]
3 Arthritis [ICD-11: FA20]
Discontinued Drug(s) 3 Discontinued Drugs  3
1 TEBUFELONE Discontinued in Phase 2
Pain
2 ZD-2138 Discontinued in Phase 2
Asthma
3 BW A4C Terminated
Arthritis
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT00205 5-lipoxygenase Bos taurus, Bovine
PT01743 Polyunsaturated fatty acid 5-lipoxygenase Rattus norvegicus, Rat