Details of the Drug Combination

General Information of Drug Combination (ID: DCTIM2Z)

Drug Combination Name
Quizartinib Idarubicin
Indication
Disease Entry Status REF
Acute Myeloid Leukemia Phase 1 [1]
Component Drugs Quizartinib   DM8Y4JS Idarubicin   DMM0XGL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Quizartinib
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [2]
leukaemia 2A60-2B33 Phase 3 [3]
Quizartinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Inhibitor [7]
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Quizartinib Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Phosphorylation [6]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Decreases Expression [6]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [8]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [8]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Expression [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [8]
Replication protein A 32 kDa subunit (RPA2) OTZ54WAF RFA2_HUMAN Increases Phosphorylation [6]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [6]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [6]
Signal transducer and activator of transcription 5B (STAT5B) OTZVPEBT STA5B_HUMAN Decreases Phosphorylation [8]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [8]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [6]
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⏷ Show the Full List of 19 DOT(s)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [4]
Acute myeloid leukaemia 2A60 Approved [5]
Adult acute monocytic leukemia N.A. Approved [4]
Childhood acute megakaryoblastic leukemia N.A. Approved [4]
Leukemia N.A. Approved [4]
Idarubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [10]
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Idarubicin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [11]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
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Idarubicin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [13]
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Idarubicin Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [9]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [14]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [9]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [15]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [16]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [9]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [17]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [9]
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⏷ Show the Full List of 9 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Acute Myeloid Leukemia DCD0UHD N. A. Phase 2 [18]
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References

1 ClinicalTrials.gov (NCT02834390) Study of Quizartinib in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
2 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216993
3 ClinicalTrials.gov (NCT02039726) An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects. U.S. National Institutes of Health.
4 Idarubicin FDA Label
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. (Ligand id: 7083).
6 Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3. Arch Toxicol. 2022 Jan;96(1):177-193. doi: 10.1007/s00204-021-03174-1. Epub 2021 Oct 19.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther. 2014 Oct;13(10):2315-27. doi: 10.1158/1535-7163.MCT-14-0258. Epub 2014 Jul 22.
9 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
12 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
13 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
14 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
15 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
16 The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
17 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
18 ClinicalTrials.gov (NCT04107727) Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)