Target Information
| Target General Information | Top | |||||
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| Target ID |
T98933
(Former ID: TTDR01227)
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| Target Name |
Thyroid hormone receptor beta (THRB)
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| Synonyms |
c-erbA-beta; c-erbA-2; THR1; Nuclear receptor subfamily 1 group A member 2; NR1A2; ERBA2
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| Gene Name |
THRB
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Hyper-lipoproteinaemia [ICD-11: 5C80] | |||||
| Function |
High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Nuclear hormone receptor that can act as a repressor or activator of transcription.
Click to Show/Hide
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| BioChemical Class |
Nuclear hormone receptor
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| UniProt ID | ||||||
| Sequence |
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQ
TTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKCKGYIPSYLDKDELCVVCGDKATGYHYR CITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWK QKRKFLPEDIGQAPIVNAPEGGKVDLEAFSHFTKIITPAITRVVDFAKKLPMFCELPCED QIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGGLGVVSDAIFDLGMSL SSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPK LLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFED Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T12PPL | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Dextrothyroxine Sodium | Drug Info | Approved | High blood cholesterol level | [2] | |
| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | BCT303 | Drug Info | Phase 2 | Hypothyroidism | [3] | |
| 2 | MB-07811 | Drug Info | Phase 2 | Hyperlipidaemia | [4] | |
| 3 | MGL-3196 | Drug Info | Phase 2 | Familial hypercholesterolemia | [5] | |
| 4 | VK-2809 | Drug Info | Phase 2 | Hypercholesterolaemia | [5] | |
| 5 | Axitirome | Drug Info | Phase 1 | Hyperlipidaemia | [6] | |
| 6 | ZYT-1 | Drug Info | Phase 1 | Lipid metabolism disorder | [7] | |
| 7 | tiratricol | Drug Info | Clinical trial | Wound healing | [8] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Dextrothyroxine Sodium | Drug Info | [1] | |||
| 2 | BCT303 | Drug Info | [9] | |||
| 3 | MB-07811 | Drug Info | [10] | |||
| 4 | Axitirome | Drug Info | [6] | |||
| 5 | ZYT-1 | Drug Info | [9] | |||
| Agonist | [+] 4 Agonist drugs | + | ||||
| 1 | MGL-3196 | Drug Info | [11] | |||
| 2 | VK-2809 | Drug Info | [5] | |||
| 3 | tiratricol | Drug Info | [12] | |||
| 4 | rT3 | Drug Info | [12] | |||
| Inhibitor | [+] 25 Inhibitor drugs | + | ||||
| 1 | (3,5-Dibromo-4-butoxy-phenyl)-acetic acid | Drug Info | [13] | |||
| 2 | (3,5-Dibromo-4-hexyloxy-phenyl)-acetic acid | Drug Info | [13] | |||
| 3 | (3,5-Dibromo-4-pentyloxy-phenyl)-acetic acid | Drug Info | [13] | |||
| 4 | (4-hexylphenyl)(oxiran-2-yl)methanone | Drug Info | [14] | |||
| 5 | (E)-1-(4-heptylphenyl)but-2-en-1-one | Drug Info | [14] | |||
| 6 | (Z)-4-(4-hexylphenylamino)-4-oxobut-2-enoic acid | Drug Info | [14] | |||
| 7 | 1-(4-(Hexyloxy)phenyl)-3-morpholinopropan-1-one | Drug Info | [15] | |||
| 8 | 1-(4-heptylphenyl)prop-2-en-1-one | Drug Info | [14] | |||
| 9 | 1-(4-hexylphenyl)-3-(propylamino)propan-1-one | Drug Info | [14] | |||
| 10 | 1-(4-hexylphenyl)-3-morpholinopropan-1-one | Drug Info | [14] | |||
| 11 | 1-(4-HEXYLPHENYL)PROP-2-EN-1-ONE | Drug Info | [16] | |||
| 12 | 1-(4-octylphenyl)prop-2-en-1-one | Drug Info | [14] | |||
| 13 | 2-hexylphenyl acrylate | Drug Info | [14] | |||
| 14 | 3-(3,5-Dibromo-4-hexyloxy-phenyl)-propionic acid | Drug Info | [13] | |||
| 15 | 3-(4-(benzyloxy)-3,5-dibromophenyl)propanoic acid | Drug Info | [17] | |||
| 16 | 3-(dibutylamino)-1-(4-hexylphenyl)propan-1-one | Drug Info | [14] | |||
| 17 | 3-(dimethylamino)-1-(4-heptylphenyl)propan-1-one | Drug Info | [15] | |||
| 18 | 3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one | Drug Info | [14] | |||
| 19 | 3-bromo-1-(4-hexylphenyl)propan-1-one | Drug Info | [14] | |||
| 20 | 4-(3-(Dimethylamino)propanoyl)-N-hexylbenzamide | Drug Info | [15] | |||
| 21 | 4-(4-hexylphenyl)-4-oxobut-2-enoic acid | Drug Info | [14] | |||
| 22 | 4-hexylphenyl propiolate | Drug Info | [14] | |||
| 23 | Cacodylate Ion | Drug Info | [18] | |||
| 24 | Detrothyronine | Drug Info | [19] | |||
| 25 | GC-24 | Drug Info | [18] | |||
| 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-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Thyroid hormone signaling pathway | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | RXR and RAR heterodimerization with other nuclear receptor | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Nuclear Receptor transcription pathway | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Hematopoietic Stem Cell Differentiation | |||||
| 3 | Nuclear Receptors | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037654) | |||||
| REF 4 | ClinicalTrials.gov (NCT00879112) Study of MB07811 in Subjects With Hypercholesterolemia. U.S. National Institutes of Health. | |||||
| REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 6 | Bacterial biosensors for screening isoform-selective ligands for human thyroid receptors alpha-1 and beta-1. FEBS Open Bio. 2012; 2: 247-253. | |||||
| REF 7 | ClinicalTrials.gov (NCT01543269) A Clinical Study to Evaluate the Safety,Tolerability and PK of ZYT1, Following Oral Administration in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 8 | 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: 2637). | |||||
| REF 9 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 10 | 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. (Target id: 589). | |||||
| REF 11 | Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-beta agonist. Atherosclerosis. 2013 Oct;230(2):373-80. | |||||
| REF 12 | Binding of 3,5,3'-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3. Mol Endocrinol. 1990 Feb;4(2):227-34. | |||||
| REF 13 | Thyroid receptor ligands. 3. Design and synthesis of 3,5-dihalo-4-alkoxyphenylalkanoic acids as indirect antagonists of the thyroid hormone receptor. J Med Chem. 2005 May 5;48(9):3114-7. | |||||
| REF 14 | Inhibitors of the interaction of a thyroid hormone receptor and coactivators: preliminary structure-activity relationships. J Med Chem. 2007 Nov 1;50(22):5269-80. | |||||
| REF 15 | Improvement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors. J Med Chem. 2009 Jul 9;52(13):3892-901. | |||||
| REF 16 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 17 | Thyroid receptor ligands. Part 7: Indirect antagonists of the thyroid hormone receptor with improved affinity. Bioorg Med Chem Lett. 2007 Apr 1;17(7):2018-21. | |||||
| REF 18 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 19 | Thyroid receptor ligands. Part 5: novel bicyclic agonist ligands selective for the thyroid hormone receptor beta. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1240-4. | |||||
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