Target type: molecularfunction
Binds to and increases the activity of the enzyme phospholipase A2. [GOC:ai]
Phospholipase A2 activator activity refers to the ability of a molecule to stimulate the enzymatic activity of phospholipase A2 (PLA2). PLA2 is a key enzyme involved in the hydrolysis of phospholipids, specifically at the sn-2 position of the glycerol backbone, releasing free fatty acids and lysophospholipids. These products play crucial roles in various cellular processes, including:
- **Signal transduction:** The released arachidonic acid serves as a precursor for the synthesis of eicosanoids, such as prostaglandins, thromboxanes, and leukotrienes, which are involved in inflammation, pain, fever, and blood clotting.
- **Membrane remodeling:** Lysophospholipids act as signaling molecules and participate in membrane remodeling by affecting membrane fluidity and permeability.
- **Lipid metabolism:** Free fatty acids released by PLA2 can be utilized for energy production or incorporated into other lipids.
PLA2 activators can exert their effects through various mechanisms, including:
- **Direct binding to PLA2:** Some activators bind directly to PLA2, inducing conformational changes that enhance its catalytic activity.
- **Altering membrane properties:** Other activators modify the membrane environment, making it more conducive for PLA2 activity. This can involve changes in membrane fluidity, charge distribution, or the presence of specific phospholipid substrates.
- **Indirect activation through signaling pathways:** Certain activators trigger intracellular signaling cascades that ultimately lead to the activation of PLA2.
The specific molecular mechanism of action for a given PLA2 activator depends on its structure and the target PLA2 isoform. Understanding these mechanisms is crucial for developing drugs that can modulate PLA2 activity for therapeutic purposes, particularly in the treatment of inflammatory diseases, cancer, and neurodegenerative disorders.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Phospholipase A-2-activating protein | A phospholipase A-2-activating protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y263] | Homo sapiens (human) |
| Caspase-3 | A caspase-3 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P42574] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| theophylline | dimethylxanthine | adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent | |
| 4-biphenylylacetic acid | biphenyl-4-ylacetic acid : A monocarboxylic acid in which one of the alpha-hydrogens is substituted by a biphenyl-4-yl group. An active metabolite of fenbufen, it is used as a topical medicine to treat muscle inflammation and arthritis. | biphenyls; monocarboxylic acid | non-steroidal anti-inflammatory drug |
| fenbufen | fenbufen: structure; RN given refers to parent cpd | 4-oxo monocarboxylic acid; biphenyls | non-steroidal anti-inflammatory drug |
| ibuprofen | Midol: combination of cinnamedrine, phenacetin, aspirin & caffeine | monocarboxylic acid | antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; radical scavenger; xenobiotic |
| indoprofen | indoprofen : A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(1-oxo-1,3-dihydroisoindol-2-yl)phenyl group. Initially used as an anti-inflammatory and analgesic, it was withdrawn from the market due to causing severe gastrointestinal bleeding. It has been subsequently found to increase production of the survival motor neuron protein. Indoprofen: A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21) | gamma-lactam; isoindoles; monocarboxylic acid | EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| ketoprofen | ketoprofen : An oxo monocarboxylic acid that consists of propionic acid substituted by a 3-benzoylphenyl group at position 2. Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. | benzophenones; oxo monocarboxylic acid | antipyretic; drug allergen; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-steroidal anti-inflammatory drug; xenobiotic |
| ketorolac | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively. ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure. Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed) | amino acid; aromatic ketone; monocarboxylic acid; pyrrolizines; racemate | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
| tiaprofenic acid | tiaprofenic acid : An aromatic ketone that is thiophene substituted at C-2 by benzoyl and at C-4 by a 1-carboxyethyl group. tiaprofenic acid: RN given refers to parent cpd; structure | aromatic ketone; monocarboxylic acid; thiophenes | drug allergen; non-steroidal anti-inflammatory drug |
| leucine | leucine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isobutyl group. Leucine: An essential branched-chain amino acid important for hemoglobin formation. | amino acid zwitterion; L-alpha-amino acid; leucine; proteinogenic amino acid; pyruvate family amino acid | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite |
| phenylalanine | L-phenylalanine : The L-enantiomer of phenylalanine. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group. Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE. | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid | algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| tryptophan | tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid; tryptophan; tryptophan zwitterion | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| homoarginine | L-homoarginine : An L-lysine derivative that is the L-enantiomer of homoarginine. | homoarginine; L-lysine derivative; non-proteinogenic L-alpha-amino acid | biomarker; EC 3.1.3.1 (alkaline phosphatase) inhibitor; human metabolite; rat metabolite; xenobiotic metabolite |
| isoquinoline-1,3,4-trione | isoquinoline-1,3,4-trione: structure in first source | ||
| n-methylisatin | N-methylisatin: structure given in first source | ||
| 1,2-benzisothiazoline-3-one | 1,2-benzisothiazoline-3-one: a preservative in water-based solutions such as paints, cutting fluids, printing inks, cleaning agents, polyvinyl chloride gloves, etc. benzo[d]isothiazol-3-one : An organic heterobicyclic compound based on a fused 1,2-thiazole and benzene bicyclic ring skeleton, with the S atom positioned adjacent to one of the positions of ring fusion. | organic heterobicyclic compound; organonitrogen heterocyclic compound | disinfectant; drug allergen; environmental contaminant; platelet aggregation inhibitor; sensitiser; xenobiotic |
| levamisole | levamisole : A 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine. Levamisole: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6) | 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole | antinematodal drug; antirheumatic drug; EC 3.1.3.1 (alkaline phosphatase) inhibitor; immunological adjuvant; immunomodulator |
| etoposide | beta-D-glucoside; furonaphthodioxole; organic heterotetracyclic compound | antineoplastic agent; DNA synthesis inhibitor | |
| 1-(3,4-dihydroxyphenyl)-2-(1-imidazolyl)ethanone | aromatic ketone | ||
| 1-benzylpiperazine | 1-benzylpiperazine : A tertiary amino compound that is piperazine substituted by a benzyl group at position 1. It is a serotonergic agonist used as a recreational drug. 1-benzylpiperazine: possesses psychomotor stimulant activity similar to dextroamphetamine; RN given refers to parent cpd; structure | N-alkylpiperazine | environmental contaminant; psychotropic drug; serotonergic agonist; xenobiotic |
| pralnacasan | pralnacasan: NSAID, ICE inhibitor & metastasis inhibitor; RN & structure in first source | ||
| naproxen | naproxen : A methoxynaphthalene that is 2-methoxynaphthalene substituted by a carboxy ethyl group at position 6. Naproxen is a non-steroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, bursitis, and for the treatment of primary dysmenorrhea. It works by inhibiting both the COX-1 and COX-2 enzymes. Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. | methoxynaphthalene; monocarboxylic acid | antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; gout suppressant; non-narcotic analgesic; non-steroidal anti-inflammatory drug; xenobiotic |
| 2-phenyl-1,2-benzisothiazol-3-(2h)-one | 2-phenyl-1,2-benzisothiazol-3-(2H)-one: structure given in first source; sulfur analog of ebselen | ||
| acetyl-aspartyl-glutamyl-valyl-aspartal | Ac-Asp-Glu-Val-Asp-H : A tetrapeptide consisting of two L-aspartic acid residues, an L-glutamyl residue and an L-valine residue with an acetyl group at the N-terminal and with the C-terminal carboxy group reduced to an aldehyde. It is an inhibitor of caspase-3/7. acetyl-aspartyl-glutamyl-valyl-aspartal: a capase inhibitor | tetrapeptide | protease inhibitor |
| 1-(3,4-dihydroxyphenyl)-2-[(4,6-dimethyl-2-pyrimidinyl)thio]ethanone | aromatic ketone | ||
| 2,5-dimethoxy-n-(quinolin-3-yl)benzenesulfonamide | 2,5-dimethoxy-N-(quinolin-3-yl)benzenesulfonamide: a tissue-nonspecific alkaline phosphatase inhibitor; structure in first source | quinolines | |
| 5-Nitroisatin | indoles | anticoronaviral agent | |
| n-acetyltyrosyl-valyl-alanyl-aspartyl aldehyde | |||
| benzyloxycarbonyl-phe-ala-fluormethylketone | cathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1). | ||
| benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone | |||
| fr 148083 | 5Z-7-oxozeaenol : A macrolide that is the 7-oxo derivative of zeaenol (the 5Z stereoisomer). Isolated from Fungi, it exhibits cytotoxic, antibacterial and inhibitory activity against NF-kappaB. | aromatic ether; macrolide; phenols; secondary alcohol; secondary alpha-hydroxy ketone | antibacterial agent; antineoplastic agent; metabolite; NF-kappaB inhibitor |
| acetic acid 2-[4-methyl-8-(4-morpholinylsulfonyl)-1,3-dioxo-2-pyrrolo[3,4-c]quinolinyl]ethyl ester | pyrroloquinoline | ||
| pf 03491390 | |||
| grassystatin a | grassystatin A: isolated from a cyanobacterium, identified as Lyngbya cf.; structure in first source | ||
| MK-8353 | MK-8353 : A member of the class of indazoles that is 1H-indazole substituted by a 6-(propan-2-yloxy)pyridin-3-yl group at position 3 and by a {[(3S)-3-(methylsulfanyl)-1-(2-{4-[4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]-3,6-dihydropyridin-1(2H)-yl}-2-oxoethyl)pyrrolidin-3-yl]carbonyl}amino group at position 5. It is a potent and selective inhibitor of ERK1 and ERK2 in vitro (IC50 values of 23.0 nM and 8.8 nM, respectively). The drug is being developed by Merck Sharp & Dohme and is currently in clinical development for the treatment of advanced/metastatic solid tumors. MK-8353: ERK inhibitor used in oncology | aromatic ether; dihydropyridine; indazoles; methyl sulfide; N-alkylpyrrolidine; pyridines; pyrrolidinecarboxamide; secondary carboxamide; tertiary carboxamide; triazoles | antineoplastic agent; apoptosis inducer; EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor |
| 2-carboxyarabinitol 1-phosphate |