Target Information
| Target General Information | Top | |||||
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| Target ID |
T61657
(Former ID: TTDR01191)
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| Target Name |
Retinoic acid receptor beta (RARB)
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| Synonyms |
RAR-epsilon; RAR-beta; Nuclear receptor subfamily 1 group B member 2; NR1B2; HBV-activated protein; HAP
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| Gene Name |
RARB
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Kaposi sarcoma [ICD-11: 2B57] | |||||
| Function |
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. Receptor for retinoic acid.
Click to Show/Hide
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| BioChemical Class |
Nuclear hormone receptor
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| UniProt ID | ||||||
| Sequence |
MTTSGHACPVPAVNGHMTHYPATPYPLLFPPVIGGLSLPPLHGLHGHPPPSGCSTPSPAT
IETQSTSSEELVPSPPSPLPPPRVYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM IYTCHRDKNCVINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKETSKQECTESYEM TAELDDLTEKIRKAHQETFPSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV EFAKRLPGFTGLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA GFGPLTDLVFTFANQLLPLEMDDTETGLLSAICLICGDRQDLEEPTKVDKLQEPLLEALK IYIRKRRPSKPHMFPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGH EPLTPSSSGNTAEHSPSISPSSVENSGVSQSPLVQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T33VZN | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Alitretinoin | Drug Info | Approved | Kaposi sarcoma | [2], [3] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Tamibarotene | Drug Info | Phase 3 | T-cell leukaemia | [4] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 8 Agonist drugs | + | ||||
| 1 | Alitretinoin | Drug Info | [1] | |||
| 2 | PMID27336223-Compound-10 | Drug Info | [7] | |||
| 3 | PMID27336223-Compound-7 | Drug Info | [7] | |||
| 4 | PMID27336223-Compound-8 | Drug Info | [7] | |||
| 5 | AC261066 | Drug Info | [8] | |||
| 6 | AC55649 | Drug Info | [8] | |||
| 7 | BMS641 | Drug Info | [10] | |||
| 8 | CD666 | Drug Info | [11] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Tamibarotene | Drug Info | [5], [6] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | AGN193109 | Drug Info | [9] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | TTNPB | Drug Info | [12] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Pathways in cancer | |||||
| 2 | Small cell lung cancer | |||||
| 3 | Non-small cell lung cancer | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Nuclear Receptor transcription pathway | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | Vitamin A and Carotenoid Metabolism | |||||
| 2 | Nuclear Receptors in Lipid Metabolism and Toxicity | |||||
| 3 | Mesodermal Commitment Pathway | |||||
| 4 | Integrated Pancreatic Cancer Pathway | |||||
| 5 | Nuclear Receptors | |||||
| References | Top | |||||
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| REF 1 | Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2645). | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | ClinicalTrials.gov (NCT04797780) SY-1425 Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome. U.S. National Institutes of Health. | |||||
| REF 5 | Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12. | |||||
| REF 6 | A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver.Obesity (Silver Spring).2013 Jan;21(1):E22-5. | |||||
| REF 7 | Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.Expert Opin Ther Pat. 2016 Aug;26(8):957-71. | |||||
| REF 8 | Discovery of a potent, orally available, and isoform-selective retinoic acid beta2 receptor agonist. J Med Chem. 2005 Dec 1;48(24):7517-9. | |||||
| REF 9 | Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000 Jan;6(1):25-58. | |||||
| REF 10 | Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004 Sep;5(9):877-82. | |||||
| REF 11 | Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83. | |||||
| REF 12 | 9-cis-retinoic acid analogues with bulky hydrophobic rings: new RXR-selective agonists. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6117-22. | |||||
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