Details of the Drug

General Information of Drug (ID: DM83HWL)

• Drug Name: L-thyroxine
• Synonyms: DL-Thyroxin; L-3,5,3',5'-Tetraiodothyronine; L-Thyroxin; L-thyroxine; Laevothyroxinum; Laevothyroxinum (acid); Levothyroxin; Levothyroxinum (acid); T4 (Hormone); Tetraiodothyronine; Tetramet; Thyratabs; Thyrax; Thyreoideum; Thyroxinal; Thyroxine (VAN); Thyroxine (l); Thyroxine I 125; Thyroxine iodine; levothyroxine; thyroxin; thyroxine; (-)-Thyroxine; 3,3',5,5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodothyronine; 51-48-9; L-T4; t4
• Affected Organisms: Humans and other mammals
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 776.87
  Logarithm of the Partition Coefficient (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C15H11I4NO4
  IUPAC Name: (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
  Canonical SMILES: C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
  InChI: XUIIKFGFIJCVMT-LBPRGKRZSA-N
  InChIKey: 1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1
• Cross-matching ID:
  PubChem CID: 5819
  ChEBI ID: CHEBI:18332
  CAS Number: 51-48-9
  UNII: Q51BO43MG4
  DrugBank ID: DB00451
  INTEDE ID: DR1950

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Substrate	[1]
Thyroxine 5-deiodinase (DIO3)	DET89OV	IOD3_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[3]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Gene/Protein Processing	[4]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Gene/Protein Processing	[5]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[6]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Gene/Protein Processing	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[6]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Gene/Protein Processing	[7]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[8]
Programmed cell death 1 ligand 1 (CD274)	OTJ0VFDL	PD1L1_HUMAN	Gene/Protein Processing	[9]

References

• [1] Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. J Endocrinol. 2001 Dec;171(3):525-32.
• [2] Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference. Endocrinology. 2003 Jun;144(6):2505-13.
• [3] Recombinant albumin and transthyretin transport proteins from two gull species and human: chlorinated and brominated contaminant binding and thyroid hormones. Environ Sci Technol. 2010 Jan 1;44(1):497-504. doi: 10.1021/es902691u.
• [4] NDAT suppresses pro-inflammatory gene expression to enhance resveratrol-induced anti-proliferation in oral cancer cells. Food Chem Toxicol. 2020 Feb;136:111092. doi: 10.1016/j.fct.2019.111092. Epub 2019 Dec 26.
• [5] Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
• [6] Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells. Food Chem Toxicol. 2019 Oct;132:110693. doi: 10.1016/j.fct.2019.110693. Epub 2019 Jul 20.
• [7] Aging and anti-aging: unexpected side effects of everyday medication through sirtuin1 modulation. Int J Mol Med. 2008 Feb;21(2):223-32.
• [8] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [9] Nano-diamino-tetrac (NDAT) inhibits PD-L1 expression which is essential for proliferation in oral cancer cells. Food Chem Toxicol. 2018 Oct;120:1-11. doi: 10.1016/j.fct.2018.06.058. Epub 2018 Jun 28.