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

General Information of Drug (ID: DMTI0ZO)

• Drug Name: Gilteritinib Drug Info
• Synonyms: 6-Ethyl-3-((3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-amino)-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide; ASP 2215; Gilteritinib; Gilteritinib (ASP-2215); Gilteritinib (ASP2215); Gilteritinib (USAN/INN); Gilteritinib [USAN:INN]; Gilteritinib(ASP2215); Xospata

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 49803313
  CAS Number: CAS 1254053-43-4
  TTD Drug ID: DMTI0ZO
  VARIDT Drug ID: DR00358

Molecule-Related Drug Atlas

Drug(s) Targeting Fms-like tyrosine kinase 3 (FLT-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[5]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[6]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[7]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[8]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[9]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[5]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[2]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[10]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[12]

Drug(s) Targeting Tyrosine-protein kinase UFO (AXL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MGCD265	DMRPCF2	Non-small-cell lung cancer	2C25.Y	Phase 2	[13]
BI-505	DMSZQHX	Multiple myeloma	2A83	Phase 2	[14]
Bemcentinib	DM0YCPL	Myelodysplastic syndrome	2A37	Phase 2	[15]
BGB-324	DMDI43Y	Breast cancer	2C60-2C65	Phase 2	[16]
Mecbotamab vedotin	DMU5KH4	Ovarian cancer	2C73	Phase 2	[17]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[2]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[18]
TP-0903	DMHTG8P	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[2]
Enapotamab vedotin	DM1PQJO	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[19]
RXDX-106	DM6NVTR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[21]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[24]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[23]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[27]

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	[28]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[29]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[30]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[31]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[32]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[35]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase UFO (AXL)	TTZPY6J	UFO_HUMAN	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [4] ClinicalTrials.gov (NCT02456883) Study to Investigate the Absorption, Metabolism and Excretion of [14C] ASP2215 in Patients With Advanced Solid Tumors.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1807).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [8] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [10] Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
• [11] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [12] Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.
• [13] Company report (Mirati Therapeutics: formerly MethylGene)
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells. J Thorac Oncol. 2020 Jun;15(6):973-999.
• [16] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1835).
• [17] Clinical pipeline report, company report or official report of BioAtla
• [18] Clinical pipeline report, company report or official report of Ono Pharmaceutical.
• [19] Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer. JCI Insight. 2019 Nov 1;4(21):e128199.
• [20] National Cancer Institute Drug Dictionary (drug name RXDX106).
• [21] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [22] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [23] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [24] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [25] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [26] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [27] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [28] 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.
• [29] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [30] 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.
• [31] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [32] 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.
• [33] 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.
• [34] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [35] 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.
• [36] 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.