ALOX15B: A Potential Drug Target and Biomarker for Inflammatory Diseases

Target Name: ALOX15B

NCBI ID: G247

ALOX15B

ALOX15B: A Potential Drug Target and Biomarker for Inflammatory Diseases

The discovery of ALOX15B, a novel lipoxygenase enzyme (15-lipoxygenase 15-LOb), has raised significant interest in its potential as a drug target and biomarker for inflammatory diseases. Lipoxygenase enzymes are involved in the production of pro-inflammatory cytokines, which play a crucial role in the development and progression of inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and chronic obstructive pulmonary disease (COPD). Therefore, targeting ALOX15B could provide new insights into the pathogenesis of these diseases and may lead to the development of novel treatments.

The Structure and Function of ALOX15B

ALOX15B is a member of the lipoxygenase family 15, which is involved in the production of pro-inflammatory cytokines. The enzyme has a molecular weight of 76 kDa and a pre- catalytic subunit of 21 kDa. The catalytic active site of the enzyme is located at the N-terminus, where it has a single transmembrane domain with a catalytic cycle of 22 amino acids. The catalytic cycle consists of three cathelicidic regions: an N-terminal alpha-helicidic region, a catalytic region, and a C-terminal region that includes a lysine residue and a glutamic acid residue, which are involved in the catalytic mechanism.

The function of ALOX15B is to catalyze the conversion of omega-3 and omega-6 fatty acids to omega-3 and omega-6 esters, which are crucial for the regulation of cellular signaling pathways, including the production of pro-inflammatory cytokines. The production of these cytokines is a critical step in the inflammatory response, and it is controlled by the activity of various enzymes, including ALOX15B.

The Prevalence of Inflammatory Diseases and the Importance of Pro-Inflammatory Cytokines

Inflammatory diseases are a leading cause of morbidity and mortality worldwide, including rheumatoid arthritis, inflammatory bowel disease, and COPD. These diseases are characterized by an excessive production of pro-inflammatory cytokines, which cause tissue damage and inflammation. The production of these cytokines is tightly regulated by various enzymes, including ALOX15B. Therefore, targeting ALOX15B has significant implications for the development of novel treatments for inflammatory diseases.

Drugs Targeting ALOX15B

The development of drugs that target ALOX15B is an attractive strategy for the treatment of inflammatory diseases. Several compounds have been shown to inhibit the activity of ALOX15B, including:

1. ALX15B-Inhibitors: Several compounds have been synthesized that inhibit the activity of ALOX15B. For example, ALX15B-1, a novel inhibitor of ALOX15B, has been shown to decrease the production of pro-inflammatory cytokines in human monocytes and to have anti-inflammatory effects in mouse models of inflammatory diseases.
2. Small Molecules: ALOX15B has also been targeted by small molecules, such as omega-3 fatty acid esters and omega-6 fatty acid esters. For instance, a novel compound, ALOX15B-2, has been shown to inhibit the production of pro-inflammatory cytokines in human monocytes and to have anti-inflammatory effects in mouse models of inflammatory diseases.

Biomarkers for ALOX15B

The detection of ALOX15B and its downstream products is critical for the diagnosis and monitoring of inflammatory diseases. Several biomarkers have been proposed for the detection of ALOX15B, including:

1. Lipoxygenase Enzyme Activities: The activity of ALOX15B can be

Protein Name: Arachidonate 15-lipoxygenase Type B

Functions: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators (PubMed:9177185, PubMed:10625675, PubMed:12704195, PubMed:17493578, PubMed:18311922, PubMed:24282679, PubMed:10542053, PubMed:24497644, PubMed:32404334) (Probable). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (PubMed:17493578, PubMed:12704195, PubMed:24282679, PubMed:9177185, PubMed:11956198, PubMed:10625675, PubMed:24497644) (Probable). Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (Probable) (PubMed:10542053, PubMed:27435673). Oxygenates arachidonyl derivatives such as 2-arachidonoylglycerol (2-AG) leading to the production and extracellular release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as a peroxisome proliferator-activated receptor alpha agonist (PubMed:18311922, PubMed:17493578, PubMed:11956198). Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates (PubMed:27145229). Participates in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) resolvin D5 ((7S,17S)-diHPDHA), which can actively down-regulate the immune response and have anti-aggregation properties with platelets (PubMed:32404334). In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids (PubMed:27435673). Has no detectable 8S-lipoxygenase activity on arachidonate but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE (Probable). May regulate progression through the cell cycle and cell proliferation (PubMed:12704195, PubMed:11839751). May also regulate cytokine secretion by macrophages and therefore play a role in the immune response (PubMed:18067895). May also regulate macrophage differentiation into proatherogenic foam cells (PubMed:22912809)

The "ALOX15B Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about ALOX15B comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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