General Information of Drug Combination (ID: DCSFOHC)

Drug Combination Name
Midostaurin Piperaquine
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs Midostaurin   DMI6E0R Piperaquine   DMT70RC
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 6.181
Bliss Independence Score: 7.666
Loewe Additivity Score: 4.715
LHighest Single Agent (HSA) Score: 9.012

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Midostaurin
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [2]
Systemic mastocytosis 2A21.0 Approved [3]
Chronic myelomonocytic leukaemia 2A40 Phase 2 [4]
Colorectal cancer 2B91.Z Phase 1 [4]
Midostaurin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Protein kinase C gamma (PRKCG) TTRFOXJ KPCG_HUMAN Inhibitor [6]
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Inhibitor [6]
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Midostaurin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Midostaurin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Midostaurin Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [9]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Response To Substance [10]
Glycophorin-A (GYPA) OTABU4YV GLPA_HUMAN Decreases Expression [11]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Activity [12]
Thrombopoietin receptor (MPL) OTZEN192 TPOR_HUMAN Increases Expression [11]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [13]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Piperaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [5]
Piperaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Piperaquine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [14]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [15]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
DD2 DCJ3LJ7 DD2 Investigative [16]
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References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
3 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
4 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: 5702).
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 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.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 Midostaurin, a novel protein kinase inhibitor for the treatment of acute myelogenous leukemia: insights from human absorption, metabolism, and excretion studies of a BDDCS II drug. Drug Metab Dispos. 2017 May;45(5):540-555.
9 Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
10 Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells. PLoS One. 2011;6(9):e25351. doi: 10.1371/journal.pone.0025351. Epub 2011 Sep 28.
11 Oral small-molecule tyrosine kinase inhibitor midostaurin (PKC412) inhibits growth and induces megakaryocytic differentiation in human leukemia cells. Toxicol In Vitro. 2009 Sep;23(6):979-85. doi: 10.1016/j.tiv.2009.06.027. Epub 2009 Jun 30.
12 FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. Oncogene. 2005 Dec 15;24(56):8259-67. doi: 10.1038/sj.onc.1208989.
13 Selective inhibition of aldo-keto reductase 1C3: a novel mechanism involved in midostaurin and daunorubicin synergism. Arch Toxicol. 2021 Jan;95(1):67-78. doi: 10.1007/s00204-020-02884-2. Epub 2020 Oct 6.
14 Eurartesim - European Medicines Agency
15 Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.
16 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.