Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGER3L)

• DTT Name: Thyroid hormone receptor beta (THRB)
• Synonyms: c-erbA-beta; c-erbA-2; THR1; Nuclear receptor subfamily 1 group A member 2; NR1A2; ERBA2
• Gene Name: THRB
• DTT Type: Successful target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: THB_HUMAN
• TTD ID: T98933
• Sequence:
  MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQ
  TTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKCKGYIPSYLDKDELCVVCGDKATGYHYR
  CITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
  DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWK
  QKRKFLPEDIGQAPIVNAPEGGKVDLEAFSHFTKIITPAITRVVDFAKKLPMFCELPCED
  QIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGGLGVVSDAIFDLGMSL
  SSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPK
  LLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFED
• Function: High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Nuclear hormone receptor that can act as a repressor or activator of transcription.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Thyroid hormone signaling pathway (hsa04919)
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

1 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	[1]

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BCT303	DMUFY4K	Hypothyroidism	5A00	Phase 2	[2]
MB-07811	DM6JTSZ	Hyperlipidaemia	5C80	Phase 2	[3]
MGL-3196	DM1HC9R	Familial hypercholesterolemia	5C80.00	Phase 2	[4]
VK-2809	DMY5NUR	Hypercholesterolaemia	5C80.0	Phase 2	[5]
Axitirome	DM6L5IP	Hyperlipidaemia	5C80	Phase 1	[6]
VK-0214	DM90GS3	X-linked Adrenoleukodystrophy	5C57	Phase 1	[7]
ZYT-1	DM1XOZK	Lipid metabolism disorder	5C52.Z	Phase 1	[2]
tiratricol	DMZO6CV	Wound healing	EL8Y	Clinical trial	[8]

26 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3,5-Dibromo-4-butoxy-phenyl)-acetic acid	DM9PDCA	Discovery agent	N.A.	Investigative	[9]
(3,5-Dibromo-4-hexyloxy-phenyl)-acetic acid	DM5GN46	Discovery agent	N.A.	Investigative	[9]
(3,5-Dibromo-4-pentyloxy-phenyl)-acetic acid	DMB5KVZ	Discovery agent	N.A.	Investigative	[9]
(4-hexylphenyl)(oxiran-2-yl)methanone	DM1WZXL	Discovery agent	N.A.	Investigative	[10]
(E)-1-(4-heptylphenyl)but-2-en-1-one	DMBXK5L	Discovery agent	N.A.	Investigative	[10]
(Z)-4-(4-hexylphenylamino)-4-oxobut-2-enoic acid	DM30YQF	Discovery agent	N.A.	Investigative	[10]
1-(4-(Hexyloxy)phenyl)-3-morpholinopropan-1-one	DMLODAM	Discovery agent	N.A.	Investigative	[11]
1-(4-heptylphenyl)prop-2-en-1-one	DMIQ0VA	Discovery agent	N.A.	Investigative	[10]
1-(4-hexylphenyl)-3-(propylamino)propan-1-one	DM5QLGH	Discovery agent	N.A.	Investigative	[10]
1-(4-hexylphenyl)-3-morpholinopropan-1-one	DMFN8T6	Discovery agent	N.A.	Investigative	[10]
1-(4-HEXYLPHENYL)PROP-2-EN-1-ONE	DMX7PJH	Discovery agent	N.A.	Investigative	[12]
1-(4-octylphenyl)prop-2-en-1-one	DM9KVBJ	Discovery agent	N.A.	Investigative	[10]
2-hexylphenyl acrylate	DMTD0IG	Discovery agent	N.A.	Investigative	[10]
3-(3,5-Dibromo-4-hexyloxy-phenyl)-propionic acid	DMDFHCU	Discovery agent	N.A.	Investigative	[9]
3-(4-(benzyloxy)-3,5-dibromophenyl)propanoic acid	DM36VA0	Discovery agent	N.A.	Investigative	[13]
3-(dibutylamino)-1-(4-hexylphenyl)propan-1-one	DM2JBQI	Discovery agent	N.A.	Investigative	[10]
3-(dimethylamino)-1-(4-heptylphenyl)propan-1-one	DMG5VMH	Discovery agent	N.A.	Investigative	[11]
3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one	DMJYCHG	Discovery agent	N.A.	Investigative	[10]
3-bromo-1-(4-hexylphenyl)propan-1-one	DM03ROH	Discovery agent	N.A.	Investigative	[10]
4-(3-(Dimethylamino)propanoyl)-N-hexylbenzamide	DMX5V9T	Discovery agent	N.A.	Investigative	[11]
4-(4-hexylphenyl)-4-oxobut-2-enoic acid	DMR9TBW	Discovery agent	N.A.	Investigative	[10]
4-hexylphenyl propiolate	DMONZ0Y	Discovery agent	N.A.	Investigative	[10]
Cacodylate Ion	DMK4XLD	Discovery agent	N.A.	Investigative	[14]
Detrothyronine	DMPCRSY	Discovery agent	N.A.	Investigative	[15]
GC-24	DMSF8B9	Hyperthyroidism	5A02	Investigative	[14]
rT3	DMWDXPN	Discovery agent	N.A.	Investigative	[8]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [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. (Target id: 589).
• [4] 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.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Bacterial biosensors for screening isoform-selective ligands for human thyroid receptors alpha-1 and beta-1. FEBS Open Bio. 2012; 2: 247-253.
• [7] Clinical pipeline report, company report or official report of Viking Therapeutics
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Improvement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors. J Med Chem. 2009 Jul 9;52(13):3892-901.
• [12] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [13] 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.
• [14] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [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.