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

General Information of Drug (ID: DML2DCR)

• Drug Name: Fedratinib hydrochloride Drug Info
• Synonyms: Fedratinib hydrochloride (USAN); TG101348(2ClH.H2O); UH9J2HBQWJ; 1374744-69-0; BCP24783; D11296; Fedratinib dihydrochloride monohydrate; UNII-UH9J2HBQWJ
• Cross-matching ID:
  PubChem CID: 67517580
  CAS Number: CAS 1374744-69-0
  TTD Drug ID: DML2DCR
  INTEDE Drug ID: DR0683

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[2]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[3]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[4]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[5]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[6]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[8]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[3]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[10]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[19]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[20]

Drug(s) Metabolized By Dimethylaniline oxidase 3 (FMO3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[21]
Ethionamide	DM8K3EI	Pulmonary tuberculosis	1B10.Z	Approved	[22]
Almotriptan malate	DMFG5ST	N. A.	N. A.	Approved	[23]
Itopride	DM7MLTR	N. A.	N. A.	Phase 3	[24]
HSR-803	DMAVIPZ	N. A.	N. A.	Phase 3	[24]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[1]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[1]
Dimethylaniline oxidase 3 (FMO3)	DEP76YL	FMO3_HUMAN	Substrate	[1]

References

• [1] FDA label of Fedratinib. The 2020 official website of the U.S. Food and Drug Administration.
• [2] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [3] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [4] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [5] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [6] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [7] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [8] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [9] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [10] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [11] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [12] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [13] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [14] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [15] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [16] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [17] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [18] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [19] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [20] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [21] Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39.
• [22] Physiologically based pharmacokinetic modeling approach to predict drug-drug interactions with ethionamide involving impact of genetic polymorphism on FMO3. J Clin Pharmacol. 2019 Jun;59(6):880-889.
• [23] Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11.
• [24] Development of a physiologically based pharmacokinetic model to predict the effects of flavin-containing monooxygenase 3 (FMO3) polymorphisms on itopride exposure. Biopharm Drug Dispos. 2017 Sep;38(6):389-393.