Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTSEPU)

• DTT 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
• DTT Type: Successful target; [1]
• Related Disease:
  Hyper-lipoproteinaemia [ICD-11: 5C80]
  Hypo-thyroidism [ICD-11: 5A00]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: THA_HUMAN
• TTD ID: T79591
• Sequence:
  MEQKPSKVECGSDPEENSARSPDGKRKRKNGQCSLKTSMSGYIPSYLDKDEQCVVCGDKA
  TGYHYRCITCEGCKGFFRRTIQKNLHPTYSCKYDSCCVIDKITRNQCQLCRFKKCIAVGM
  AMDLVLDDSKRVAKRKLIEQNRERRRKEEMIRSLQQRPEPTPEEWDLIHIATEAHRSTNA
  QGSHWKQRRKFLPDDIGQSPIVSMPDGDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFS
  ELPCEDQIILLKGCCMEIMSLRAAVRYDPESDTLTLSGEMAVKREQLKNGGLGVVSDAIF
  ELGKSLSAFNLDDTEVALLQAVLLMSTDRSGLLCVDKIEKSQEAYLLAFEHYVNHRKHNI
  PHFWPKLLMKEREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQL
  GEAGSLQGPVLQHQSPKSPQQRLLELLHRSGILHARAVCGEDDSSEADSPSSSEEEPEVC
  EDLAGNAASP
• 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.
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dextrothyroxine Sodium	DMBVEC7	High blood cholesterol level	5C80.00	Approved	[2]
Levothyroxine	DMHN027	Hypothyroidism	5A00	Approved	[3], [4]
Liothyronine	DM6IR3P	Hypothyroidism	5A00	Approved	[1], [4]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BCT303	DMUFY4K	Hypothyroidism	5A00	Phase 2	[5]
tiratricol	DMZO6CV	Wound healing	EL8Y	Clinical trial	[6]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3,5-Dibromo-4-hexyloxy-phenyl)-acetic acid	DM5GN46	Discovery agent	N.A.	Investigative	[7]
(E)-1-(4-heptylphenyl)but-2-en-1-one	DMBXK5L	Discovery agent	N.A.	Investigative	[8]
(Z)-4-(4-hexylphenylamino)-4-oxobut-2-enoic acid	DM30YQF	Discovery agent	N.A.	Investigative	[8]
1-(4-hexylphenyl)-3-morpholinopropan-1-one	DMFN8T6	Discovery agent	N.A.	Investigative	[8]
3-(3,5-Dibromo-4-hexyloxy-phenyl)-propionic acid	DMDFHCU	Discovery agent	N.A.	Investigative	[7]
3-(4-(benzyloxy)-3,5-dibromophenyl)propanoic acid	DM36VA0	Discovery agent	N.A.	Investigative	[9]
3-(dibutylamino)-1-(4-hexylphenyl)propan-1-one	DM2JBQI	Discovery agent	N.A.	Investigative	[8]
3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one	DMJYCHG	Discovery agent	N.A.	Investigative	[8]
3-bromo-1-(4-hexylphenyl)propan-1-one	DM03ROH	Discovery agent	N.A.	Investigative	[8]
4-(4-hexylphenyl)-4-oxobut-2-enoic acid	DMR9TBW	Discovery agent	N.A.	Investigative	[8]
4-hexylphenyl propiolate	DMONZ0Y	Discovery agent	N.A.	Investigative	[8]
Detrothyronine	DMPCRSY	Discovery agent	N.A.	Investigative	[10]
rT3	DMWDXPN	Discovery agent	N.A.	Investigative	[6]

References

• [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.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23.
• [4] Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59.
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.