Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of retinoic acid receptor signaling pathway activity. [GOC:dgh]
The retinoic acid receptor (RAR) signaling pathway plays a crucial role in regulating various developmental and physiological processes. Retinoic acid (RA), the active metabolite of vitamin A, acts as a ligand for RARs. RARs are nuclear receptors that form heterodimers with retinoid X receptors (RXRs) upon binding to RA. These heterodimers bind to specific DNA sequences known as retinoic acid response elements (RAREs) in the promoters of target genes. Binding of the RAR/RXR heterodimer to RAREs initiates the recruitment of coactivator proteins, leading to the transcription of downstream target genes. The regulation of RAR signaling pathway involves several intricate mechanisms:
1. **Ligand availability**: The concentration of RA, derived from dietary vitamin A, directly impacts the activation of RARs. RA synthesis and degradation pathways tightly control the availability of the ligand.
2. **Post-translational modifications**: RARs undergo phosphorylation and acetylation, which can influence their transcriptional activity. These modifications are regulated by various signaling pathways, including the MAPK and PI3K pathways.
3. **Co-regulator interactions**: The recruitment of coactivators and corepressors to RARs is crucial for transcriptional regulation. Coactivators enhance gene transcription, while corepressors suppress it. The interplay between these factors fine-tunes the transcriptional response.
4. **Cross-talk with other signaling pathways**: RAR signaling pathway interacts with other signaling pathways, such as the Wnt, TGF-β, and Notch pathways. These interactions allow for fine-tuning of gene expression and cellular responses.
5. **MicroRNAs**: MicroRNAs (miRNAs) can regulate the expression of RARs and their downstream target genes. miRNAs act as fine-tuners of the pathway, modulating the levels of specific proteins involved in RAR signaling.
6. **Feedback loops**: RAR signaling pathway exhibits feedback loops that help maintain homeostasis. For example, some target genes of RARs encode proteins that can inhibit or activate the pathway, ensuring that the response remains within a defined range.
7. **Genetic variations**: Genetic variations in RAR genes or in genes encoding proteins involved in the pathway can impact the sensitivity of the pathway to RA. These variations contribute to individual differences in RA metabolism, signaling, and response.
The precise regulation of RAR signaling pathway is essential for maintaining normal development, growth, and homeostasis. Dysregulation of this pathway can contribute to various diseases, including cancer, birth defects, and metabolic disorders. Understanding the intricate mechanisms of RAR signaling is crucial for developing therapeutic strategies targeting this pathway for the treatment of various diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Aldo-keto reductase family 1 member C3 | An aldo-keto reductase family 1 member C3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P42330] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| berberine | alkaloid antibiotic; berberine alkaloid; botanical anti-fungal agent; organic heteropentacyclic compound | antilipemic drug; antineoplastic agent; antioxidant; EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD(+))] inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor; EC 1.21.3.3 (reticuline oxidase) inhibitor; EC 2.1.1.116 [3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase] inhibitor; EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor; EC 2.7.11.10 (IkappaB kinase) inhibitor; EC 3.1.1.4 (phospholipase A2) inhibitor; EC 3.1.1.7 (acetylcholinesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor; EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; geroprotector; hypoglycemic agent; metabolite; potassium channel blocker | |
| flufenamic acid | flufenamic acid : An aromatic amino acid consisting of anthranilic acid carrying an N-(trifluoromethyl)phenyl substituent. An analgesic and anti-inflammatory, it is used in rheumatic disorders. Flufenamic Acid: An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16) | aromatic amino acid; organofluorine compound | antipyretic; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| flurbiprofen | flurbiprofen : A monocarboxylic acid that is a 2-fluoro-[1,1'-biphenyl-4-yl] moiety linked to C-2 of propionic acid. A non-steroidal anti-inflammatory, analgesic and antipyretic, it is used as a pre-operative anti-miotic as well as orally for arthritis or dental pain. Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE. | fluorobiphenyl; monocarboxylic acid | antipyretic; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| gliclazide | Gliclazide: An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion. | N-sulfonylurea | hypoglycemic agent; insulin secretagogue; radical scavenger |
| glimepiride | glimepiride: structure given in first source | sulfonamide | |
| 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 |
| indomethacin | indometacin : A member of the class of indole-3-acetic acids that is indole-3-acetic acid in which the indole ring is substituted at positions 1, 2 and 5 by p-chlorobenzoyl, methyl, and methoxy groups, respectively. A non-steroidal anti-inflammatory drug, it is used in the treatment of musculoskeletal and joint disorders including osteoarthritis, rheumatoid arthritis, gout, bursitis and tendinitis. Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. | aromatic ether; indole-3-acetic acids; monochlorobenzenes; N-acylindole | analgesic; drug metabolite; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; gout suppressant; non-steroidal anti-inflammatory drug; xenobiotic; xenobiotic metabolite |
| meclofenamic acid | meclofenamic acid : An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,6-dichloro-3-methylphenyl group. A non-steroidal anti-inflammatory drug, it is used as the sodium salt for the treatment of dysmenorrhoea (painful periods), osteoarthritis and rheumatoid arthritis. Meclofenamic Acid: A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis. | aminobenzoic acid; organochlorine compound; secondary amino compound | analgesic; anticonvulsant; antineoplastic agent; antipyretic; antirheumatic drug; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-steroidal anti-inflammatory drug |
| mefenamic acid | mefenamic acid : An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,3-dimethylphenyl group. Although classed as a non-steroidal anti-inflammatory drug, its anti-inflammatory properties are considered to be minor. It is used to relieve mild to moderate pain, including headaches, dental pain, osteoarthritis and rheumatoid arthritis. Mefenamic Acid: A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. | aminobenzoic acid; secondary amino compound | analgesic; antipyretic; antirheumatic drug; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-steroidal anti-inflammatory drug; xenobiotic |
| fenamic acid | fenamic acid : An aminobenzoic acid that is the N-phenyl derivative of anthranilic acid. It acts as a parent skeleton for the synthesis of several non-steroidal anti-inflammatory drugs. fenamic acid: has chloride and potassium channel-blocking activity; RN given refers to parent cpd | aminobenzoic acid; secondary amino compound | membrane transport modulator |
| medroxyprogesterone acetate | 20-oxo steroid; 3-oxo-Delta(4) steroid; acetate ester; corticosteroid; steroid ester | adjuvant; androgen; antineoplastic agent; antioxidant; female contraceptive drug; inhibitor; progestin; synthetic oral contraceptive | |
| benzoic anhydride | 2-benzoylbenzoic acid: structure in first source | ||
| 3,5-dichlorosalicylic acid | 3,5-dichlorosalicylic acid: structure in first source | chlorobenzoic acid | |
| 3,5-dibromosalicylic acid | 3,5-dibromosalicylic acid: structure in first source | ||
| 3-phenoxybenzoic acid | 3-phenoxybenzoic acid : A phenoxybenzoic acid in which the phenoxy group is meta to the carboxy group. It is a metabolite of pyrethroid insecticides. 3-phenoxybenzoic acid: metabolite associated with exposure to pyrethroid insecticides | phenoxybenzoic acid | human xenobiotic metabolite; marine xenobiotic metabolite |
| 6-methoxy-2-naphthylacetic acid | (6-methoxy-2-naphthyl)acetic acid : A monocarboxylic acid consisting of 2-naphthylacetic acid having a methoxy substituent at the 6-position. The active metabolite of the prodrug nabumetone. 6-methoxy-2-naphthylacetic acid: major metabolite of nabumetone; inhibits cyclooxygenase-2 (COX-2) | methoxynaphthalene; monocarboxylic acid | drug metabolite; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; xenobiotic metabolite |
| dexibuprofen | dexibuprofen: structure in first source | ibuprofen | non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| octyl gallate | gallate ester | food antioxidant; hypoglycemic agent; plant metabolite | |
| 4-methoxybenzophenone | 4-methoxybenzophenone: structure in first source | ||
| 5-methoxy-methylindoleacetic acid | 5-methoxy-methylindoleacetic acid: structure given in first source | indole-3-acetic acids | |
| 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'-hydroxyflavanone | |||
| tolfenamic acid | tolfenamic acid : An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 3-chloro-2-methylphenyl group. Tolfenamic acid is used specifically for relieving the pain of migraine. It also shows anticancer activity. tolfenamic acid: structure | aminobenzoic acid; organochlorine compound; secondary amino compound | EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; EC 2.7.1.33 (pantothenate kinase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| diclofenac sodium | diclofenac sodium : The sodium salt of diclofenac. Diclofenac Sodium: The sodium form of DICLOFENAC. It is used for its analgesic and anti-inflammatory properties. | organic sodium salt | |
| linoleic acid | linoleic acid : An octadecadienoic acid in which the two double bonds are at positions 9 and 12 and have Z (cis) stereochemistry. Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed) | octadecadienoic acid; omega-6 fatty acid | algal metabolite; Daphnia galeata metabolite; plant metabolite |
| jasmonic acid | jasmonic acid : An oxo monocarboxylic acid that is (3-oxocyclopentyl)acetic acid substituted by a (2Z)-pent-2-en-1-yl group at position 2 of the cyclopentane ring. jasmonic acid: a derivative of alpha-linolenic acid that has a role in plant response to herbivory analogous to the role of prostanoids in inflammation in mammals; | oxo monocarboxylic acid | jasmonates; plant metabolite |
| caffeic acid phenethyl ester | phenethyl caffeate : An alkyl caffeate ester in which 2-phenylethyl is the alkyl component. | alkyl caffeate ester | anti-inflammatory agent; antibacterial agent; antineoplastic agent; antioxidant; antiviral agent; immunomodulator; metabolite; neuroprotective agent |
| tazettine | tazettine: from Amaryllidaceae | indole alkaloid; indole alkaloid fundamental parent | |
| artepillin c | artepillin C: RN refers to (E)-isomer | ||
| drupanin | Drupanin: anti-oxidant and anti-cancer; structure in first source | ||
| n-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide | boceprevir : A synthetic tripeptide consisting of N-(tert-butylcarbamoyl)-3-methyl-L-valyl, a cyclopropyl-fused prolyl and 3-amino-4-cyclobutyl-2-oxobutanamide residues joined in sequence. Used for treatment of chronic hepatitis C virus genotype 1 infection. | tripeptide; ureas | antiviral drug; hepatitis C protease inhibitor; peptidomimetic |
| mf63 compound | MF63 compound: a phenanthrene imidazole identified as a potent, selective, and orally active mPGES-1 inhibitor; structure in first source | ||
| buparlisib | NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source | aminopyridine; aminopyrimidine; morpholines; organofluorine compound | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| dinaciclib | pyrazolopyrimidine |