9-cis-Retinoic acid (T3D2884)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (25)XML
Targets (25)
Record Information
Version2.0
Creation Date2009-07-21 20:27:36 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2884
Identification
Common Name9-cis-Retinoic acid
ClassSmall Molecule
DescriptionTretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).
Compound Type
  • Antineoplastic Agent
  • Cell Stimulant and Proliferant
  • Drug
  • Ester
  • Food Toxin
  • Keratolytic Agent
  • Metabolite
  • Nutraceutical
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(all-e)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid
15-Apo-beta-caroten-15-oate
15-Apo-beta-caroten-15-oic acid
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexene-1-yl)-2,4,6,8-nonatetraenoic acid (ecl)
9-cis-Retinoate
9-cis-Tretinoin
9-Retinoate
9-Retinoic acid
Aberel
Aberela
AGN 100335
Airol
Aknoten
Alitretinoin
all trans Retinoic acid
all trans-Retinoic acid
all-(e)-Retinoic acid
All-trans- Vitamin A1 acid
All-trans-b-retinoate
All-trans-b-retinoic acid
All-trans-beta-retinoate
All-trans-beta-retinoic acid
all-trans-Retinoic acid
all-trans-Tretinoin
All-trans-vitamin a acid
all-trans-Vitamin a1 acid
alpha-Vitaminsyre
Amnesteem
ATRA
Atragen
Atralin
Avita
Avitoin
B-Retinoate
B-Retinoic acid
beta-Retinoate
beta-Retinoic acid
Claravis
Dermairol
Effederm
Epi-aberel
Eudyna
Isotretinoin retinoate
Isotretinoin retinoic acid
Kétrel
Panretin
Panretin gel
Panretyn
Panrexin
Refissa
Renova
Retacnyl
Retin a
Retin-a
Retin-a micro
Retinoate
Retinoic acid
Retinova
Retionic acid
Retisol-a
Ro 1-5488
Solage
Sotret
Stieva-a
Trans-retinoate
Trans-retinoic acid
trans-Vitamin a acid
Tretin m
Tretin-X
TRETIN.X
Tretinoin
Tretinoin/all-trans retinoate
Tretinoin/all-trans retinoic acid
Tretinoina
Trétinoïne
Tretinoinum
Tretinon
Vesanoid
Vesnaroid
Vitamin A acid
Vitinoin
Chemical FormulaC20H28O2
Average Molecular Mass300.435 g/mol
Monoisotopic Mass300.209 g/mol
CAS Registry Number302-79-4
IUPAC Name(2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
Traditional Namealitretinoin
SMILES[H]/C(=C(/[H])\C(\C)=C(/[H])C(O)=O)/C(/[H])=C(\C)/C(/[H])=C(\[H])C1=C(C)CCCC1(C)C
InChI IdentifierInChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+
InChI KeyInChIKey=SHGAZHPCJJPHSC-YCNIQYBTSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Retinoic acid
  • Diterpenoid
  • Retinoid skeleton
  • Medium-chain fatty acid
  • Branched fatty acid
  • Methyl-branched fatty acid
  • Fatty acyl
  • Unsaturated fatty acid
  • Fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Retinol MetabolismSMP00074 map00830
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point181°C
Boiling PointNot Available
Solubility<0.1 g/100 mL
LogP6.3
Predicted Properties
PropertyValueSource
Water Solubility0.0048 g/LALOGPS
logP5.66ALOGPS
logP5.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.79 m³·mol⁻¹ChemAxon
Polarizability35.89 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-2190000000-86aaab132a5b092ebf102017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0a4i-5139000000-29caedb85908ca2b99f42017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0uei-0494000000-28e6366fdd47e8ba21172016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052r-2980000000-3e7fc78de83c238304162016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-5900000000-ef4d86f8bcf86959f7942016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052b-0090000000-e07ffb4c1e5c63ab1b592016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052b-0090000000-a0a8411213bbd25432432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000i-3690000000-97e6a74798dd69c30ad12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052b-0090000000-5f942e3b870e7bd0121b2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0190000000-22b445382d39772800452021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-016r-4900000000-0005b37f6d54a42a84f62021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0zir-0973000000-3040e9e4a1a5448efbcb2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-060c-1950000000-f3b9c9b378f60b8c49a92021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ar3-5910000000-de22eb65f274483f3f982021-09-22View Spectrum
Toxicity Profile
Route of Exposure1-31% (topical)
Mechanism of ToxicityTretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.
MetabolismHepatic Half Life: 0.5-2 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant); For the topical treatment of acne vulgaris, flat warts and other skin conditions (psoriasis, ichthyosis congenita, icthyosis vulgaris, lamellar icthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier's disease), and basal cell carcinomas.); For palliative therapy to improve fine wrinkling, mottled hyperpigmentation, roughness associated with photodamage.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00755
HMDB IDHMDB02369
PubChem Compound ID444795
ChEMBL IDCHEMBL38
ChemSpider ID5337
KEGG IDC00777
UniProt IDNot Available
OMIM ID180190 , 180220 , 180230 , 180231 , 180240 , 194550 , 300217 , 600825 , 601340 , 601384 , 601972 , 601973 , 602239 , 602943 , 602978 , 604138 , 604256 , 604650 , 605090 , 605092 , 605207 , 605697 , 605698 , 605699 , 605948 , 605949 , 606586 , 607026 , 607159 , 607642 , 609036 , 609243 , 609244 , 609631 , 609848 , 609987 , 610617 , 610745
ChEBI ID15367
BioCyc IDRETINOATE
CTD IDNot Available
Stitch IDTretinoin
PDB ID9CR
ACToR IDNot Available
Wikipedia LinkTretinoin
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72. [3165295 ]
  2. Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704-9. [2224119 ]
  3. Sanz MA: Treatment of acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2006:147-55. [17124054 ]
  4. Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, Roth MD: A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med. 2002 Mar 1;165(5):718-23. [11874821 ]
  5. Roth MD, Connett JE, D'Armiento JM, Foronjy RF, Friedman PJ, Goldin JG, Louis TA, Mao JT, Muindi JR, O'Connor GT, Ramsdell JW, Ries AL, Scharf SM, Schluger NW, Sciurba FC, Skeans MA, Walter RE, Wendt CH, Wise RA: Feasibility of retinoids for the treatment of emphysema study. Chest. 2006 Nov;130(5):1334-45. [17099008 ]
  6. Mertz JR, Shang E, Piantedosi R, Wei S, Wolgemuth DJ, Blaner WS: Identification and characterization of a stereospecific human enzyme that catalyzes 9-cis-retinol oxidation. A possible role in 9-cis-retinoic acid formation. J Biol Chem. 1997 May 2;272(18):11744-9. [9115228 ]
  7. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Retinoic acid receptor gamma
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.01 uMATG_DR5_CISAttagene
AC500.03 uMATG_RARg_TRANSAttagene
References
  1. Curtin JC, Spinella MJ: p53 in human embryonal carcinoma: identification of a transferable, transcriptional repression domain in the N-terminal region of p53. Oncogene. 2005 Feb 24;24(9):1481-90. [15674351 ]
  2. Parrella E, Gianni M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E: Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24. Epub 2006 Jun 20. [16788091 ]
  3. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. Retinoic acid receptor RXR-alpha
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular Weight:
50810.835 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.008 uMNot AvailableBindingDB 31892
Inhibitory0.0084 uMNot AvailableBindingDB 31892
Inhibitory0.012 uMNot AvailableBindingDB 31892
IC500.029 uMNot AvailableBindingDB 31892
IC500.032 uMNot AvailableBindingDB 31892
Dissociation0.0015 uMNot AvailableBindingDB 31892
Dissociation0.003 uMNot AvailableBindingDB 31892
Dissociation0.008 uMNot AvailableBindingDB 31892
Dissociation0.009 uMNot AvailableBindingDB 31892
Dissociation0.013 uMNot AvailableBindingDB 31892
Dissociation0.05 uMNot AvailableBindingDB 31892
Dissociation0.24 uMNot AvailableBindingDB 31892
AC500.03 uMATG_RXRa_TRANSAttagene
References
  1. Sussman F, de Lera AR: Ligand recognition by RAR and RXR receptors: binding and selectivity. J Med Chem. 2005 Oct 6;48(20):6212-9. [16190748 ]
  2. Muccio DD, Brouillette WJ, Alam M, Vaezi MF, Sani BP, Venepally P, Reddy L, Li E, Norris AW, Simpson-Herren L, Hill DL: Conformationally defined 6-s-trans-retinoic acid analogs. 3. Structure-activity relationships for nuclear receptor binding, transcriptional activity, and cancer chemopreventive activity. J Med Chem. 1996 Sep 13;39(19):3625-35. [8809153 ]
  3. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  4. Farmer LJ, Zhi L, Jeong S, Lamph WW, Osburn DL, Croston G, Flatten KS, Heyman RA, Nadzan AM: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid. Bioorg Med Chem Lett. 2003 Jan 20;13(2):261-4. [12482435 ]
  5. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  6. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  7. Dominguez B, Vega MJ, Sussman F, de Lera AR: Synthesis and characterization of a new RXR agonist based on the 6-tert-butyl-1,1-dimethylindanyl structure. Bioorg Med Chem Lett. 2002 Sep 16;12(18):2607-9. [12182871 ]
  8. Zhan Y, Du X, Chen H, Liu J, Zhao B, Huang D, Li G, Xu Q, Zhang M, Weimer BC, Chen D, Cheng Z, Zhang L, Li Q, Li S, Zheng Z, Song S, Huang Y, Ye Z, Su W, Lin SC, Shen Y, Wu Q: Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nat Chem Biol. 2008 Sep;4(9):548-56. doi: 10.1038/nchembio.106. [18690216 ]
  9. Cavasotto CN, Liu G, James SY, Hobbs PD, Peterson VJ, Bhattacharya AA, Kolluri SK, Zhang XK, Leid M, Abagyan R, Liddington RC, Dawson MI: Determinants of retinoid X receptor transcriptional antagonism. J Med Chem. 2004 Aug 26;47(18):4360-72. [15317450 ]
  10. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  11. Canan Koch SS, Dardashti LJ, Hebert JJ, White SK, Croston GE, Flatten KS, Heyman RA, Nadzan AM: Identification of the first retinoid X, receptor homodimer antagonist. J Med Chem. 1996 Aug 16;39(17):3229-34. [8765503 ]
  12. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  13. Umemiya H, Fukasawa H, Ebisawa M, Eyrolles L, Kawachi E, Eisenmann G, Gronemeyer H, Hashimoto Y, Shudo K, Kagechika H: Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers. J Med Chem. 1997 Dec 19;40(26):4222-34. [9435893 ]
  14. Mizuguchi Y, Wada A, Nakagawa K, Ito M, Okano T: Antitumoral activity of 13-demethyl or 13-substituted analogues of all-trans retinoic acid and 9-cis retinoic acid in the human myeloid leukemia cell line HL-60. Biol Pharm Bull. 2006 Sep;29(9):1803-9. [16946489 ]
  15. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
3. Retinoic acid receptor alpha
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0223 uMNot AvailableBindingDB 31892
IC500.007 uMNot AvailableBindingDB 31892
Dissociation0.011 uMNot AvailableBindingDB 31892
Dissociation0.09 uMNot AvailableBindingDB 31892
Dissociation0.093 uMNot AvailableBindingDB 31892
AC500.03 uMATG_RARa_TRANSAttagene
AC500.31 uMNVS_NR_hRARa_AgonistNovascreen
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  2. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  3. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  4. Farmer LJ, Zhi L, Jeong S, Lamph WW, Osburn DL, Croston G, Flatten KS, Heyman RA, Nadzan AM: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid. Bioorg Med Chem Lett. 2003 Jan 20;13(2):261-4. [12482435 ]
  5. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  6. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  7. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
4. Retinoic acid receptor RXR-beta
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
Gene Name:
RXRB
Uniprot ID:
P28702
Molecular Weight:
56921.38 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0038 uMNot AvailableBindingDB 31892
Inhibitory0.0074 uMNot AvailableBindingDB 31892
Inhibitory0.009 uMNot AvailableBindingDB 31892
IC500.012 uMNot AvailableBindingDB 31892
Dissociation0.011 uMNot AvailableBindingDB 31892
Dissociation0.015 uMNot AvailableBindingDB 31892
Dissociation0.035 uMNot AvailableBindingDB 31892
AC507.27 uMATG_RXRb_TRANSAttagene
References
  1. Stafslien DK, Vedvik KL, De Rosier T, Ozers MS: Analysis of ligand-dependent recruitment of coactivator peptides to RXRbeta in a time-resolved fluorescence resonance energy transfer assay. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):82-9. Epub 2006 Dec 20. [17184907 ]
  2. Redfern CP: Enhancing enhancers: new complexities in the retinoid regulation of gene expression. Biochem J. 2004 Oct 1;383(Pt 1):e1-2. [15379735 ]
  3. Nagasawa H, Takahashi S, Kobayashi A, Tazawa H, Tashima Y, Sato K: Effect of retinoic acid on murine preosteoblastic MC3T3-E1 cells. J Nutr Sci Vitaminol (Tokyo). 2005 Oct;51(5):311-8. [16392701 ]
  4. Schrage K, Koopmans G, Joosten EA, Mey J: Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury. Eur J Neurosci. 2006 Jan;23(2):285-95. [16420438 ]
  5. Hoegberg P, Schmidt CK, Fletcher N, Nilsson CB, Trossvik C, Gerlienke Schuur A, Brouwer A, Nau H, Ghyselinck NB, Chambon P, Hakansson H: Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms. Chem Biol Interact. 2005 Sep 10;156(1):25-39. [16109390 ]
  6. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  7. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  8. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  9. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  10. Umemiya H, Fukasawa H, Ebisawa M, Eyrolles L, Kawachi E, Eisenmann G, Gronemeyer H, Hashimoto Y, Shudo K, Kagechika H: Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers. J Med Chem. 1997 Dec 19;40(26):4222-34. [9435893 ]
  11. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  12. Canan Koch SS, Dardashti LJ, Hebert JJ, White SK, Croston GE, Flatten KS, Heyman RA, Nadzan AM: Identification of the first retinoid X, receptor homodimer antagonist. J Med Chem. 1996 Aug 16;39(17):3229-34. [8765503 ]
  13. Steidl U, Schroeder T, Steidl C, Kobbe G, Graef T, Bork S, Pechtel S, Kliszewski S, Kuendgen A, Rohr UP, Fenk R, Schroeder M, Haase D, Haas R, Kronenwett R: Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera. Ann N Y Acad Sci. 2005 Jun;1044:94-108. [15958702 ]
  14. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
  15. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
5. Retinoic acid receptor gamma
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.001 uMNot AvailableBindingDB 31892
Inhibitory0.02 uMNot AvailableBindingDB 31892
IC500.017 uMNot AvailableBindingDB 31892
Dissociation0.0008 uMNot AvailableBindingDB 31892
Dissociation0.022 uMNot AvailableBindingDB 31892
Dissociation0.148 uMNot AvailableBindingDB 31892
Dissociation0.15 uMNot AvailableBindingDB 31892
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Reddy AP, Chen JY, Zacharewski T, Gronemeyer H, Voorhees JJ, Fisher GJ: Characterization and purification of human retinoic acid receptor-gamma 1 overexpressed in the baculovirus-insect cell system. Biochem J. 1992 Nov 1;287 ( Pt 3):833-40. [1332684 ]
  4. Kamei Y, Kawada T, Kazuki R, Sugimoto E: Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Biochem J. 1993 Aug 1;293 ( Pt 3):807-12. [8394693 ]
  5. Borger DR, Mi Y, Geslani G, Zyzak LL, Batova A, Engin TS, Pirisi L, Creek KE: Retinoic acid resistance at late stages of human papillomavirus type 16-mediated transformation of human keratinocytes arises despite intact retinoid signaling and is due to a loss of sensitivity to transforming growth factor-beta. Virology. 2000 May 10;270(2):397-407. [10792999 ]
  6. Sussman F, de Lera AR: Ligand recognition by RAR and RXR receptors: binding and selectivity. J Med Chem. 2005 Oct 6;48(20):6212-9. [16190748 ]
  7. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  8. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  9. Farmer LJ, Zhi L, Jeong S, Lamph WW, Osburn DL, Croston G, Flatten KS, Heyman RA, Nadzan AM: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid. Bioorg Med Chem Lett. 2003 Jan 20;13(2):261-4. [12482435 ]
  10. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  11. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  12. Umemiya H, Fukasawa H, Ebisawa M, Eyrolles L, Kawachi E, Eisenmann G, Gronemeyer H, Hashimoto Y, Shudo K, Kagechika H: Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers. J Med Chem. 1997 Dec 19;40(26):4222-34. [9435893 ]
  13. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  14. Klucik J, Xiao YD, Hammond PS, Harris R, Schmitt JD: Targacept active conformation search: a new method for predicting the conformation of a ligand bound to its protein target. J Med Chem. 2004 Dec 30;47(27):6831-9. [15615532 ]
  15. Parrella E, Gianni M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E: Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24. Epub 2006 Jun 20. [16788091 ]
Target Details
6. Retinoic acid receptor RXR-gamma
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
Gene Name:
RXRG
Uniprot ID:
P48443
Molecular Weight:
50870.72 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.011 uMNot AvailableBindingDB 31892
Inhibitory0.013 uMNot AvailableBindingDB 31892
Inhibitory0.014 uMNot AvailableBindingDB 31892
IC500.004 uMNot AvailableBindingDB 31892
Dissociation0.014 uMNot AvailableBindingDB 31892
Dissociation0.016 uMNot AvailableBindingDB 31892
Dissociation0.03 uMNot AvailableBindingDB 31892
References
  1. Schrage K, Koopmans G, Joosten EA, Mey J: Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury. Eur J Neurosci. 2006 Jan;23(2):285-95. [16420438 ]
  2. Koda T, Imai H, Morita M: Antiestrogenic activity of vitamin A in in vivo uterotrophic assay. Life Sci. 2007 Feb 13;80(10):945-9. Epub 2006 Nov 22. [17161848 ]
  3. He JC, Lu TC, Fleet M, Sunamoto M, Husain M, Fang W, Neves S, Chen Y, Shankland S, Iyengar R, Klotman PE: Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway. J Am Soc Nephrol. 2007 Jan;18(1):93-102. Epub 2006 Dec 20. [17182884 ]
  4. Day RM, Lee YH, Park AM, Suzuki YJ: Retinoic acid inhibits airway smooth muscle cell migration. Am J Respir Cell Mol Biol. 2006 Jun;34(6):695-703. Epub 2006 Feb 2. [16456186 ]
  5. Wang J, Yen A: A novel retinoic acid-responsive element regulates retinoic acid-induced BLR1 expression. Mol Cell Biol. 2004 Mar;24(6):2423-43. [14993281 ]
  6. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  7. Farmer LJ, Zhi L, Jeong S, Lamph WW, Osburn DL, Croston G, Flatten KS, Heyman RA, Nadzan AM: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid. Bioorg Med Chem Lett. 2003 Jan 20;13(2):261-4. [12482435 ]
  8. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  9. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  10. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  11. Umemiya H, Fukasawa H, Ebisawa M, Eyrolles L, Kawachi E, Eisenmann G, Gronemeyer H, Hashimoto Y, Shudo K, Kagechika H: Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers. J Med Chem. 1997 Dec 19;40(26):4222-34. [9435893 ]
  12. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  13. Canan Koch SS, Dardashti LJ, Hebert JJ, White SK, Croston GE, Flatten KS, Heyman RA, Nadzan AM: Identification of the first retinoid X, receptor homodimer antagonist. J Med Chem. 1996 Aug 16;39(17):3229-34. [8765503 ]
  14. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
Target Details
7. Retinoic acid receptor beta
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50488.63 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0109 uMNot AvailableBindingDB 31892
IC500.007 uMNot AvailableBindingDB 31892
Dissociation0.007 uMNot AvailableBindingDB 31892
Dissociation0.097 uMNot AvailableBindingDB 31892
Dissociation0.1 uMNot AvailableBindingDB 31892
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  2. Vuligonda V, Garst ME, Chandraratna RA: Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands. Bioorg Med Chem Lett. 1999 Feb 22;9(4):589-94. [10098670 ]
  3. Farmer LJ, Zhi L, Jeong S, Lamph WW, Osburn DL, Croston G, Flatten KS, Heyman RA, Nadzan AM: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid. Bioorg Med Chem Lett. 2003 Jan 20;13(2):261-4. [12482435 ]
  4. Vuligonda V, Thacher SM, Chandraratna RA: Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem. 2001 Jul 5;44(14):2298-303. [11428923 ]
  5. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA: Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem. 1994 Feb 4;37(3):408-14. [8308867 ]
  6. Zhang L, Nadzan AM, Heyman RA, Love DL, Mais DE, Croston G, Lamph WW, Boehm MF: Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells. J Med Chem. 1996 Jul 5;39(14):2659-63. [8709094 ]
  7. Steidl U, Schroeder T, Steidl C, Kobbe G, Graef T, Bork S, Pechtel S, Kliszewski S, Kuendgen A, Rohr UP, Fenk R, Schroeder M, Haase D, Haas R, Kronenwett R: Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera. Ann N Y Acad Sci. 2005 Jun;1044:94-108. [15958702 ]
Target Details
8. Retinal dehydrogenase 1
General Function:
Retinal dehydrogenase activity
Specific Function:
Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity).
Gene Name:
ALDH1A1
Uniprot ID:
P00352
Molecular Weight:
54861.44 Da
References
  1. Gidlof AC, Ocaya P, Olofsson PS, Torma H, Sirsjo A: Differences in retinol metabolism and proliferative response between neointimal and medial smooth muscle cells. J Vasc Res. 2006;43(4):392-8. Epub 2006 Jul 6. [16837774 ]
  2. Mic FA, Molotkov A, Molotkova N, Duester G: Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004 Oct;231(2):270-7. [15366004 ]
  3. Everts HB, King LE Jr, Sundberg JP, Ong DE: Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation. J Invest Dermatol. 2004 Aug;123(2):258-63. [15245423 ]
  4. Matt N, Dupe V, Garnier JM, Dennefeld C, Chambon P, Mark M, Ghyselinck NB: Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development. 2005 Nov;132(21):4789-800. Epub 2005 Oct 5. [16207763 ]
  5. Kim H, Lapointe J, Kaygusuz G, Ong DE, Li C, van de Rijn M, Brooks JD, Pollack JR: The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer. Cancer Res. 2005 Sep 15;65(18):8118-24. [16166285 ]
Target Details
9. Retinal dehydrogenase 2
General Function:
Retinal dehydrogenase activity
Specific Function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently (By similarity).
Gene Name:
ALDH1A2
Uniprot ID:
O94788
Molecular Weight:
56723.495 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Mic FA, Sirbu IO, Duester G: Retinoic acid synthesis controlled by Raldh2 is required early for limb bud initiation and then later as a proximodistal signal during apical ectodermal ridge formation. J Biol Chem. 2004 Jun 18;279(25):26698-706. Epub 2004 Apr 6. [15069081 ]
  3. Bordelon T, Montegudo SK, Pakhomova S, Oldham ML, Newcomer ME: A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II. J Biol Chem. 2004 Oct 8;279(41):43085-91. Epub 2004 Aug 7. [15299009 ]
  4. Mic FA, Molotkov A, Molotkova N, Duester G: Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004 Oct;231(2):270-7. [15366004 ]
  5. Doxakis E, Davies AM: Retinoic acid negatively regulates GDNF and neurturin receptor expression and responsiveness in embryonic chicken sympathetic neurons. Mol Cell Neurosci. 2005 Aug;29(4):617-27. [15950488 ]
Target Details
10. Fas-binding factor 1
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Maiti TK, Ghosh KS, Debnath J, Dasgupta S: Binding of all-trans retinoic acid to human serum albumin: fluorescence, FT-IR and circular dichroism studies. Int J Biol Macromol. 2006 May 30;38(3-5):197-202. Epub 2006 Mar 6. [16569428 ]
  2. N'soukpoe-Kossi CN, Sedaghat-Herati R, Ragi C, Hotchandani S, Tajmir-Riahi HA: Retinol and retinoic acid bind human serum albumin: stability and structural features. Int J Biol Macromol. 2007 Apr 10;40(5):484-90. Epub 2006 Nov 24. [17184834 ]
  3. Karnaukhova E: Interactions of human serum albumin with retinoic acid, retinal and retinyl acetate. Biochem Pharmacol. 2007 Mar 15;73(6):901-10. Epub 2006 Dec 2. [17217919 ]
Target Details
11. Nuclear receptor subfamily 0 group B member 1
General Function:
Transcription factor binding
Specific Function:
Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity).
Gene Name:
NR0B1
Uniprot ID:
P51843
Molecular Weight:
51717.185 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
12. Retinoic acid receptor responder protein 1
General Function:
Not Available
Specific Function:
Inhibitor of the cytoplasmic carboxypeptidase AGBL2, may regulate the alpha-tubulin tyrosination cycle.
Gene Name:
RARRES1
Uniprot ID:
P49788
Molecular Weight:
33284.865 Da
References
  1. Youssef EM, Chen XQ, Higuchi E, Kondo Y, Garcia-Manero G, Lotan R, Issa JP: Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers. Cancer Res. 2004 Apr 1;64(7):2411-7. [15059893 ]
  2. Zirn B, Samans B, Spangenberg C, Graf N, Eilers M, Gessler M: All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo. Oncogene. 2005 Aug 4;24(33):5246-51. [15897880 ]
Target Details
13. Retinoic acid-induced protein 3
General Function:
G-protein coupled receptor activity
Specific Function:
Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218).
Gene Name:
GPRC5A
Uniprot ID:
Q8NFJ5
Molecular Weight:
40250.69 Da
References
  1. Xu J, Tian J, Shapiro SD: Normal lung development in RAIG1-deficient mice despite unique lung epithelium-specific expression. Am J Respir Cell Mol Biol. 2005 May;32(5):381-7. Epub 2005 Jan 27. [15677768 ]
  2. Inoue S, Nambu T, Shimomura T: The RAIG family member, GPRC5D, is associated with hard-keratinized structures. J Invest Dermatol. 2004 Mar;122(3):565-73. [15086536 ]
Target Details
14. Cellular retinoic acid-binding protein 2
General Function:
Transporter activity
Specific Function:
Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.
Gene Name:
CRABP2
Uniprot ID:
P29373
Molecular Weight:
15692.925 Da
References
  1. Steidl U, Schroeder T, Steidl C, Kobbe G, Graef T, Bork S, Pechtel S, Kliszewski S, Kuendgen A, Rohr UP, Fenk R, Schroeder M, Haase D, Haas R, Kronenwett R: Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera. Ann N Y Acad Sci. 2005 Jun;1044:94-108. [15958702 ]
Target Details
15. Lipocalin-1
General Function:
Cysteine-type endopeptidase inhibitor activity
Specific Function:
Could play a role in taste reception. Could be necessary for the concentration and delivery of sapid molecules in the gustatory system. Can bind various ligands, with chemical structures ranging from lipids and retinoids to the macrocyclic antibiotic rifampicin and even to microbial siderophores. Exhibits an extremely wide ligand pocket.
Gene Name:
LCN1
Uniprot ID:
P31025
Molecular Weight:
19249.845 Da
References
  1. Breustedt DA, Schonfeld DL, Skerra A: Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. Epub 2006 Jan 6. [16461020 ]
Target Details
16. Odorant-binding protein 2a
General Function:
Odorant binding
Specific Function:
Probably binds and transports small hydrophobic volatile molecules with a higher affinity for aldehydes and large fatty acids.
Gene Name:
OBP2A
Uniprot ID:
Q9NY56
Molecular Weight:
19318.245 Da
References
  1. Breustedt DA, Schonfeld DL, Skerra A: Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. Epub 2006 Jan 6. [16461020 ]
Target Details
17. Prostaglandin-H2 D-isomerase
General Function:
Transporter activity
Specific Function:
Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.
Gene Name:
PTGDS
Uniprot ID:
P41222
Molecular Weight:
21028.665 Da
References
  1. Breustedt DA, Schonfeld DL, Skerra A: Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. Epub 2006 Jan 6. [16461020 ]
Target Details
18. Protein AMBP
General Function:
Small molecule binding
Specific Function:
Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin, and lysosomal granulocytic elastase. Inhibits calcium oxalate crystallization.Trypstatin is a trypsin inhibitor.
Gene Name:
AMBP
Uniprot ID:
P02760
Molecular Weight:
38999.215 Da
References
  1. Breustedt DA, Schonfeld DL, Skerra A: Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. Epub 2006 Jan 6. [16461020 ]
Target Details
19. Retinol-binding protein 4
General Function:
Retinol transporter activity
Specific Function:
Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.
Gene Name:
RBP4
Uniprot ID:
P02753
Molecular Weight:
23009.8 Da
References
  1. Breustedt DA, Schonfeld DL, Skerra A: Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. Epub 2006 Jan 6. [16461020 ]
Target Details
20. Peroxisome proliferator-activated receptor gamma
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.12 uMTox21_PPARg_BLA_Agonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
21. Estrogen receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.84 uMATG_ERa_TRANSAttagene
AC500.22 uMATG_ERE_CISAttagene
AC507.82 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
22. Nuclear receptor subfamily 4 group A member 2
General Function:
Zinc ion binding
Specific Function:
Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity).
Gene Name:
NR4A2
Uniprot ID:
P43354
Molecular Weight:
66590.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.30 uMATG_NURR1_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
23. Bile acid receptor
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.61 uMATG_IR1_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
24. D(4) dopamine receptor
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.89 uMNVS_GPCR_hDRD4.4Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
25. Cytochrome P450 1A1
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.39 uMNVS_ADME_hCYP1A1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]