Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMVJD1A)

• Drug Name: Triiodo-l-thyronine Drug Info
• Synonyms: Reverse Tri-Iodothyronine; Triiodothyronine, reverse; (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3-iodophenyl]propanoic acid; (S)-2-Amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3-iodophenyl)propanoic acid; 3,3',5'-Triiodo-L-thyronine; 3,3',5'-Triiodothyronine; 5817-39-0; 3,3',5'-Triiodo-l-thyronine; REVERSE TRIIODOTHYRONINE; Reverse T3; 8NZ4Y08T96; CHEBI:11684; DSSTox_CID_26908; DSSTox_GSID_46908; DSSTox_RID_82006; L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3-iodo-; Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3-iodo-; UNII-8NZ4Y08T96
• Cross-matching ID:
  PubChem CID: 644280
  ChEBI ID: CHEMBL11684
  CAS Number: CAS 5817-39-0
  TTD Drug ID: DMVJD1A
  INTEDE Drug ID: DR1947

Molecule-Related Drug Atlas

Drug(s) Metabolized By Sulfotransferase 1A1 (SULT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[4]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[5]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[6]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[7]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[8]
Warfarin	DMJYCVW	Atrial fibrillation	BC81.3	Approved	[9]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[10]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[1]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[11]
Benzyl alcohol	DMBVYDI	Head and body lice	1G00.0	Approved	[12]

Drug(s) Affected By Type II iodothyronine deiodinase (DIO2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[15]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[16]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[19]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[20]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[21]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[22]

Drug(s) Affected By Type I iodothyronine deiodinase (DIO1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[23]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[20]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[16]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[20]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[28]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Sulfotransferase 1A1 (SULT1A1) Main DME	DEYWLRK	ST1A1_HUMAN	Substrate	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Type I iodothyronine deiodinase (DIO1)	OTFYLYJ0	IOD1_HUMAN	Regulation of Drug Effects	[2]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Gene/Protein Processing	[3]

References

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• [3] Disruption of type 2 iodothyronine deiodinase activity in cultured human glial cells by polybrominated diphenyl ethers. Chem Res Toxicol. 2015 Jun 15;28(6):1265-74. doi: 10.1021/acs.chemrestox.5b00072. Epub 2015 Jun 2.
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• [10] Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.
• [11] Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
• [12] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
• [13] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [14] The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes. 2007 Mar;56(3):767-76. doi: 10.2337/db06-1488.
• [15] Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology. 2009 Apr;150(4):1976-83. doi: 10.1210/en.2008-0938. Epub 2008 Nov 26.
• [16] Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
• [17] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [18] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [19] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [20] Screening the ToxCast Phase 1, Phase 2, and e1k Chemical Libraries for Inhibitors of Iodothyronine Deiodinases. Toxicol Sci. 2019 Apr 1;168(2):430-442. doi: 10.1093/toxsci/kfy302.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [23] Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways. Toxicol Appl Pharmacol. 2012 Apr 1;260(1):81-8. doi: 10.1016/j.taap.2012.01.029. Epub 2012 Feb 8.
• [24] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [25] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [26] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [27] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [28] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [29] Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid. 2005 Aug;15(8):835-40. doi: 10.1089/thy.2005.15.835.