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

General Information of Drug (ID: DM1UE67)

• Drug Name: TOCOTRIENOL Drug Info
• Synonyms: 2-Methyl-2-[[4,8,12-trimethyl-3(E),7(E),11(E)]-tridecatrienyl]-3,4-dihydro-2H-benzo[b]pyran-6-ol

Indication

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Approved	[1]

• Cross-matching ID:
  PubChem CID: 9929901
  CAS Number: CAS 6829-55-6
  TTD Drug ID: DM1UE67

Molecule-Related Drug Atlas

Drug(s) Targeting HMG-CoA reductase (HMGCR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[4]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[5]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[6]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[7]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[8]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[5]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[9]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[5]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[10]
Teriflunomide	DMQ2FKJ	Hyperlipidaemia	5C80	Approved	[9]

Drug(s) Affected By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[11]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[13]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[13]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[14]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[15]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[16]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Drug Response	[3]

References

• [1] Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures. J Radiat Res. 2013 Nov 1;54(6):973-88.
• [2] Inhibitory effect of delta-tocotrienol, a HMG CoA reductase inhibitor, on monocyte-endothelial cell adhesion. J Nutr Sci Vitaminol (Tokyo). 2002 Oct;48(5):332-7.
• [3] Vitamin E analogues differentially inhibit human cytochrome P450 3A (CYP3A)-mediated oxidative metabolism of lithocholic acid: Impact of -tocotrienol on lithocholic acid cytotoxicity. Toxicology. 2019 Jul 1;423:62-74. doi: 10.1016/j.tox.2019.05.005. Epub 2019 May 15.
• [4] A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
• [5] Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
• [6] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [7] Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia. Arzneimittelforschung. 2001;51(3):197-203.
• [8] New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
• [9] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [10] Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
• [11] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [12] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
• [13] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [14] Contribution of CYP3A5 to hepatic and renal ifosfamide N-dechloroethylation. Drug Metab Dispos. 2005 Jul;33(7):1074-81. doi: 10.1124/dmd.104.002279. Epub 2005 Apr 8.
• [15] Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.
• [16] Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity. J Toxicol Sci. 2017;42(3):343-348.
• [17] 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.
• [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] Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines. Drug Metab Dispos. 2013 Feb;41(2):281-90.