ALOX5 arachidonate 5-lipoxygenase
ENSG00000012779 · protein coding · Open Targets profile
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:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). 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:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:32841762, PubMed:8615788). 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). {ECO:0000250|UniProtKB:P48999, ECO:0000269|PubMed:17114001, ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:21233389, ECO:0000269|PubMed:22516296, ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:31664810, ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:32841762, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7281100153923035 (upper bound 0.8965399861335754). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 85 registry trials, updated in the last three years, of the most advanced drugs against ALOX5 (meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, PF-4191834), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Vipul JairathWestern University; London Health Sciences Centre · 2 of 2 trials Phase 2+
- Ying HuangChildren's Hospital of Fudan University · 2 of 2 trials Phase 2+
- Catherine ReenaersStudy Principal Investigator · 1 of 1 trials Phase 2+
- Christian Johana J Baños HernándezUniversity of Guadalajara · 1 of 1 trials Phase 2+
- Dalia R Mohammed ElAfifyTanta University · 1 of 1 trials Phase 2+
- Dirk ElewautUZ Ghent · 1 of 1 trials Phase 2+
- Emily RosenfeldRutgers Robert Wood Johnson Medical School · 1 of 1 trials Phase 2+
- Faculty O DentistryCairo University · 1 of 1 trials Phase 2+
- Filip Van den BoschUZ Ghent · 1 of 1 trials Phase 2+
- Gordon MoranUniversity of Nottingham · 1 of 1 trials Phase 2+
- Gulraiz IqbalKing Edward Medical University · 1 of 1 trials Phase 2+
- Hans-Georg WirschingUniversity Hospital and University of Zurich · 1 of 1 trials Phase 2+
- Hussein A ElAmin HammamAssiut University · 1 of 1 trials Phase 2+
- James R O'DellUniversity of Nebraska · 1 of 1 trials Phase 2+
- Jonathan SamuelsNYU Langone Health · 1 of 1 trials Phase 2+
Registry trials of meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, PF-4191834 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 68 of 75 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 10 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
38 trials of drugs against ALOX5 were stopped early; 4 give no reason
Terminated, withdrawn and suspended interventional trials of meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, PF-4191834, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 38.
- withdrawn · 2025-08-12 · AbbVie · Mesalamine“strategic considerations”
- terminated · 2025-02-21 · Boston Medical Center · matched by the registry's drug synonyms“Unable to recruit adequate numbers of participants to answer the research question.”
- withdrawn · 2023-02-01 · Xijing Hospital of Digestive Diseases · matched by the registry's drug synonyms“Lack of funds”
- withdrawn · 2023-02-01 · Xijing Hospital of Digestive Diseases · matched by the registry's drug synonyms“Lack of funds”
- terminated · 2022-06-01 · Prof. Arie Levine · matched by the registry's drug synonyms“It is not possible to continue the study”
- withdrawn · 2021-10-01 · Schneider Children's Medical Center, Israel · matched by the registry's drug synonyms“Difficulty to enroll patients”
- terminated · 2021-07-27 · Jawaharlal Institute of Postgraduate Medical Education & Research · Sulfasalazine“Due to time constraints, the study was halted prematurely”
- terminated · 2021-04-06 · Julio Ramirez · matched by the registry's drug synonyms“Not enough patient enrollment and lack of staffing”
- terminated · 2021-03-19 · Assembly Biosciences · matched by the registry's drug synonyms“Sponsor Decision”
- terminated · 2020-01-18 · VSL Pharmaceuticals · Mesalamine“Administrative reasons”
- terminated · 2019-11-18 · University of Minnesota · Zileuton“Lack of feasibility due to low recruitment”
- terminated · 2019-10-15 · Endeavor Health · matched by the registry's drug synonyms“Insufficient enrollment”
- terminated · 2019-08-28 · Forest Laboratories · matched by the registry's drug synonyms“The decision was taken solely for business/administrative reasons, no safety considerations entered into this. Ongoing randomized patients to complete.”
- terminated · 2019-04-18 · Christoph Gasche · mesalamine 2400 MG (5-ASA), mesalamine 1200 MG“Due to poor patient recruitment and insufficient financing.”
- terminated · 2019-01-29 · Annette Langseder · matched by the registry's drug synonyms“none enrolled in second arm, therfore no analysis”
- terminated · 2018-08-22 · Massachusetts General Hospital · Sulfasalazine“poor enrollment”
- terminated · 2018-01-12 · Milton S. Hershey Medical Center · Mesalamine“Lack of accrual”
- terminated · 2017-07-24 · Dr. Falk Pharma GmbH · matched by the registry's drug synonymsNo reason given
- terminated · 2017-07-21 · Dr. Falk Pharma GmbH · matched by the registry's drug synonyms“Stopped due to futility.”
- withdrawn · 2017-07-02 · National Institute of Allergy and Infectious Diseases (NIAID) · MesalamineNo reason given
- terminated · 2017-06-15 · Prometheus Laboratories · matched by the registry's drug synonyms“LT-02 did not appear to help induce remission of UC”
- terminated · 2017-04-13 · Merck Sharp & Dohme LLC · matched by the registry's drug synonyms“Due to slow recruitment the study was stopped prematurely.”
- terminated · 2017-04-12 · Merck Sharp & Dohme LLC · DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89.“Slow Enrollment”
- terminated · 2017-03-27 · Sandoz · Mesalamine“Enrollment difficulties”
- terminated · 2017-02-23 · Pfizer · Sulfasalazine“Study terminated on 13 April 2016 for business reasons. No safety and/or efficacy concerns contributed to the termination of the study”
Paediatric incentives and obligations for ALOX5's drugs
For meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, PF-4191834: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · ALOX5 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, pf-4191834Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, pf-4191834Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, pf-4191834Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, pf-4191834Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 39 interventional studies of meclofenamic acid, meclofenamate, balsalazide, olsalazine, zileuton, sulfasalazine, mesalamine, atreleuton, pf-4191834 include patients under 18; 3 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 11 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.