Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBBIRHZ)

• DOT Name: Thyroid hormone receptor beta (THRB)
• Synonyms: Nuclear receptor subfamily 1 group A member 2; c-erbA-2; c-erbA-beta
• Gene Name: THRB
• Related Disease:
  Thyroid hormone resistance, generalized, autosomal dominant
  Obsolete resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
  Thyroid hormone resistance, generalized, autosomal recessive
• UniProt ID: THB_HUMAN
• PDB ID: 1BSX; 1N46; 1NAX; 1NQ0; 1NQ1; 1NQ2; 1NUO; 1Q4X; 1R6G; 1XZX; 1Y0X; 2J4A; 2NLL; 2PIN; 3D57; 3GWS; 3IMY; 3JZC; 4ZO1; 6KKB; 6KKE; 6KNU; 6KNV; 6KNW; 7WLX; 7WMG; 7WMH; 7WMJ; 7WML; 7WMN; 7WMO
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQ
  TTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKCKGYIPSYLDKDELCVVCGDKATGYHYR
  CITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
  DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWK
  QKRKFLPEDIGQAPIVNAPEGGKVDLEAFSHFTKIITPAITRVVDFAKKLPMFCELPCED
  QIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGGLGVVSDAIFDLGMSL
  SSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPK
  LLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFED
• Function: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway:
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid hormone resistance, generalized, autosomal dominant	DISF731E	Strong	Autosomal dominant	[1]
Obsolete resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta	DIS6VDRE	Supportive	Autosomal recessive	[2]
Thyroid hormone resistance, generalized, autosomal recessive	DISZBNI8	Limited	Autosomal recessive	[3]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Thyroid hormone receptor beta (THRB).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Thyroid hormone receptor beta (THRB).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Thyroid hormone receptor beta (THRB).	[18]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thyroid hormone receptor beta (THRB).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thyroid hormone receptor beta (THRB).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thyroid hormone receptor beta (THRB).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Thyroid hormone receptor beta (THRB).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Thyroid hormone receptor beta (THRB).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Thyroid hormone receptor beta (THRB).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Thyroid hormone receptor beta (THRB).	[12]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Thyroid hormone receptor beta (THRB).	[13]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Thyroid hormone receptor beta (THRB).	[14]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Thyroid hormone receptor beta (THRB).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Thyroid hormone receptor beta (THRB).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Thyroid hormone receptor beta (THRB).	[16]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Thyroid hormone receptor beta (THRB).	[17]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Thyroid hormone receptor beta (THRB).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Thyroid hormone receptor beta (THRB).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Thyroid hormone receptor beta (THRB).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Thyroid hormone receptor beta (THRB).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Thyroid hormone receptor beta (THRB).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thyroid hormone receptor beta (THRB).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the activity of Thyroid hormone receptor beta (THRB).	[24]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Thyroid hormone receptor beta (THRB).	[25]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Thyroid hormone receptor beta (THRB).	[26]
L-thyroxine	DM83HWL	Investigative	L-thyroxine increases the expression of Thyroid hormone receptor beta (THRB).	[27]
Triiodo-l-thyronine	DMVJD1A	Investigative	Triiodo-l-thyronine increases the activity of Thyroid hormone receptor beta (THRB).	[29]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
EPI-001	DMYWV81	Investigative	EPI-001 affects the binding of Thyroid hormone receptor beta (THRB).	[28]

References

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