Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T79591
(Former ID: TTDS00381)
|
|||||
| Target Name |
Thyroid hormone receptor alpha (THRA)
|
|||||
| Synonyms |
V-erbA-related protein 7; THRA2; THRA1; Nuclear receptor subfamily 1 group A member 1; NR1A1; ERBA1; EAR7; EAR-7; C-erbA-alpha; C-erbA-1
|
|||||
| Gene Name |
THRA
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Hyper-lipoproteinaemia [ICD-11: 5C80] | |||||
| 2 | Hypo-thyroidism [ICD-11: 5A00] | |||||
| Function |
High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription.
Click to Show/Hide
|
|||||
| BioChemical Class |
Nuclear hormone receptor
|
|||||
| UniProt ID | ||||||
| Sequence |
MEQKPSKVECGSDPEENSARSPDGKRKRKNGQCSLKTSMSGYIPSYLDKDEQCVVCGDKA
TGYHYRCITCEGCKGFFRRTIQKNLHPTYSCKYDSCCVIDKITRNQCQLCRFKKCIAVGM AMDLVLDDSKRVAKRKLIEQNRERRRKEEMIRSLQQRPEPTPEEWDLIHIATEAHRSTNA QGSHWKQRRKFLPDDIGQSPIVSMPDGDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFS ELPCEDQIILLKGCCMEIMSLRAAVRYDPESDTLTLSGEMAVKREQLKNGGLGVVSDAIF ELGKSLSAFNLDDTEVALLQAVLLMSTDRSGLLCVDKIEKSQEAYLLAFEHYVNHRKHNI PHFWPKLLMKEREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQL GEAGSLQGPVLQHQSPKSPQQRLLELLHRSGILHARAVCGEDDSSEADSPSSSEEEPEVC EDLAGNAASP Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Dextrothyroxine Sodium | Drug Info | Approved | High blood cholesterol level | [2] | |
| 2 | Levothyroxine | Drug Info | Approved | Hypothyroidism | [3], [4] | |
| 3 | Liothyronine | Drug Info | Approved | Hypothyroidism | [2] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | BCT303 | Drug Info | Phase 2 | Hypothyroidism | [5] | |
| 2 | tiratricol | Drug Info | Clinical trial | Wound healing | [6] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Dextrothyroxine Sodium | Drug Info | [7] | |||
| 2 | BCT303 | Drug Info | [10] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | Levothyroxine | Drug Info | [8], [9] | |||
| 2 | Liothyronine | Drug Info | [1], [9] | |||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | tiratricol | Drug Info | [11] | |||
| 2 | rT3 | Drug Info | [11] | |||
| Inhibitor | [+] 12 Inhibitor drugs | + | ||||
| 1 | (3,5-Dibromo-4-hexyloxy-phenyl)-acetic acid | Drug Info | [12] | |||
| 2 | (E)-1-(4-heptylphenyl)but-2-en-1-one | Drug Info | [13] | |||
| 3 | (Z)-4-(4-hexylphenylamino)-4-oxobut-2-enoic acid | Drug Info | [13] | |||
| 4 | 1-(4-hexylphenyl)-3-morpholinopropan-1-one | Drug Info | [13] | |||
| 5 | 3-(3,5-Dibromo-4-hexyloxy-phenyl)-propionic acid | Drug Info | [12] | |||
| 6 | 3-(4-(benzyloxy)-3,5-dibromophenyl)propanoic acid | Drug Info | [14] | |||
| 7 | 3-(dibutylamino)-1-(4-hexylphenyl)propan-1-one | Drug Info | [13] | |||
| 8 | 3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one | Drug Info | [13] | |||
| 9 | 3-bromo-1-(4-hexylphenyl)propan-1-one | Drug Info | [13] | |||
| 10 | 4-(4-hexylphenyl)-4-oxobut-2-enoic acid | Drug Info | [13] | |||
| 11 | 4-hexylphenyl propiolate | Drug Info | [13] | |||
| 12 | Detrothyronine | Drug Info | [15] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| 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 | [+] 2 WikiPathways | + | ||||
| 1 | Endochondral Ossification | |||||
| 2 | Nuclear Receptors | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Evaluation of thyroid hormone action in a case of generalized resistance to thyroid hormone with chronic thyroiditis: discovery of a novel heterozy... Endocr J. 2007 Dec;54(5):727-32. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | 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: 4627). | |||||
| REF 4 | Current methodology to assess bioequivalence of levothyroxine sodium products is inadequate. AAPS J. 2005 Mar 30;7(1):E42-6. | |||||
| REF 5 | 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 6 | 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 7 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 8 | Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23. | |||||
| REF 9 | Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. | |||||
| REF 10 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 11 | 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 12 | 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 13 | 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 14 | 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 15 | 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. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.