Details of the Drug

General Information of Drug (ID: DMWQ4MZ)

Drug Name
Gilteritinib
Synonyms
UNII-66D92MGC8M; 66D92MGC8M; Gilteritinib [USAN:INN]; Gilteritinib(ASP2215); Gilteritinib (USAN/INN); Gilteritinib (ASP2215); Gilteritinib (ASP-2215); SCHEMBL282229; GTPL8708; MolPort-038-934-933; BDBM144315; C29H44N8O3; 3694AH; s7754; AKOS030234455; ZINC113476229; DB12141; CS-3885; KS-0000064E; AS-35199
Indication
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [1], [2]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 552.7
Topological Polar Surface Area (xlogp) 3.5
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C29H44N8O3
IUPAC Name
6-ethyl-3-[3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide
Canonical SMILES
CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC(=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)OC)NC5CCOCC5
InChI
InChI=1S/C29H44N8O3/c1-4-23-28(31-20-9-17-40-18-10-20)34-29(26(33-23)27(30)38)32-21-5-6-24(25(19-21)39-3)37-11-7-22(8-12-37)36-15-13-35(2)14-16-36/h5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34)
InChIKey
GYQYAJJFPNQOOW-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
49803313
ChEBI ID
CHEBI:145372
CAS Number
1254053-43-4
DrugBank ID
DB12141
TTD ID
D04KZY
INTEDE ID
DR0772
ACDINA ID
D01124

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-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute myeloid leukaemia
ICD Disease Classification 2A60
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Fms-like tyrosine kinase 3 (FLT-3) DTT FLT3 2.11E-01 -0.05 -0.16
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Gilteritinib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Ivosidenib DM8S6T7 Major Increased risk of prolong QT interval by the combination of Gilteritinib and Ivosidenib. Acute myeloid leukaemia [2A60] [29]
Coadministration of a Drug Treating the Disease Different from Gilteritinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Gilteritinib and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [30]
Oliceridine DM6MDCF Moderate Increased risk of prolong QT interval by the combination of Gilteritinib and Oliceridine. Acute pain [MG31] [31]
Levalbuterol DM5YBO1 Moderate Increased risk of prolong QT interval by the combination of Gilteritinib and Levalbuterol. Asthma [CA23] [32]
Troleandomycin DMUZNIG Major Decreased metabolism of Gilteritinib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [31]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Gilteritinib and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [33]
Deutetrabenazine DMUPFLI Moderate Increased risk of prolong QT interval by the combination of Gilteritinib and Deutetrabenazine. Dystonic disorder [8A02] [34]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Gilteritinib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [31]
Tazemetostat DMWP1BH Moderate Increased metabolism of Gilteritinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [31]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Gilteritinib caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [35]
Pralsetinib DMWU0I2 Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Pralsetinib. Lung cancer [2C25] [30]
Ubrogepant DM749I3 Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [36]
Rimegepant DMHOAUG Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Rimegepant. Migraine [8A80] [37]
Siponimod DM2R86O Major Increased risk of ventricular arrhythmias by the combination of Gilteritinib and Siponimod. Multiple sclerosis [8A40] [30]
Ozanimod DMT6AM2 Major Increased risk of ventricular arrhythmias by the combination of Gilteritinib and Ozanimod. Multiple sclerosis [8A40] [38]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Gilteritinib caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [35]
Rucaparib DM9PVX8 Moderate Increased risk of prolong QT interval by the combination of Gilteritinib and Rucaparib. Ovarian cancer [2C73] [31]
Triclabendazole DMPWGBR Moderate Increased risk of prolong QT interval by the combination of Gilteritinib and Triclabendazole. Parasitic worm infestation [1F90] [31]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Gilteritinib and Macimorelin. Pituitary gland disorder [5A60-5A61] [39]
Lefamulin DME6G97 Major Decreased metabolism of Gilteritinib caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [40]
Darolutamide DMV7YFT Minor Decreased clearance of Gilteritinib due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [41]
Voxelotor DMCS6M5 Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Voxelotor. Sickle-cell disorder [3A51] [35]
Larotrectinib DM26CQR Moderate Decreased metabolism of Gilteritinib caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [35]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [42]
Betrixaban DM2C4RF Moderate Decreased clearance of Gilteritinib due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [43]
⏷ Show the Full List of 24 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Hydroxypropyl cellulose E00632 Not Available Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Haematite red E00236 14833 Colorant
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Gilteritinib 40 mg tablet 40 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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 ClinicalTrials.gov (NCT02456883) Study to Investigate the Absorption, Metabolism and Excretion of [14C] ASP2215 in Patients With Advanced Solid Tumors.
4 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.
5 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
6 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.
7 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
8 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.
9 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.
10 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
11 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.
12 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.
13 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).
14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
15 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
16 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.
17 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
18 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.
19 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
20 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.
21 Company report (Mirati Therapeutics: formerly MethylGene)
22 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
23 AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells. J Thorac Oncol. 2020 Jun;15(6):973-999.
24 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).
25 Clinical pipeline report, company report or official report of Ono Pharmaceutical.
26 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.
27 National Cancer Institute Drug Dictionary (drug name RXDX106).
28 First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer. J Hematol Oncol. 2020 Jan 16;13(1):6.
29 Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
30 Cerner Multum, Inc. "Australian Product Information.".
31 Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
32 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
33 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
34 Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
35 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
36 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
37 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
38 Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
39 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
40 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
41 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
42 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
43 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.