General Information of Drug Combination (ID: DC15SJL)

Drug Combination Name
Carfilzomib Artemisinin
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs Carfilzomib   DM48K0X Artemisinin   DMOY7W3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 4.714
Bliss Independence Score: 2.923
Loewe Additivity Score: 0.692
LHighest Single Agent (HSA) Score: 3.342

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Carfilzomib
Disease Entry ICD 11 Status REF
Multiple myeloma 2A83 Approved [2]
Plasma cell myeloma 2A83.1 Approved [3]
Small-cell lung cancer 2C25.Y Phase 1/2 [4]
Carfilzomib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proteasome (PS) TTU7ZMG NOUNIPROTAC Modulator [7]
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Carfilzomib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Carfilzomib Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [10]
Cytochrome c oxidase subunit 8A, mitochondrial (COX8A) OTU0NR39 COX8A_HUMAN Decreases Expression [10]
Basigin (BSG) OTD0CVEC BASI_HUMAN Decreases Expression [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
C-X-C chemokine receptor type 4 (CXCR4) OTUFSBX2 CXCR4_HUMAN Decreases Expression [11]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [10]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Response To Substance [12]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Artemisinin
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [5]
Artemisinin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [5]
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Artemisinin Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [14]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [15]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [13]
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Artemisinin Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Activity [15]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [16]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [16]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [17]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [17]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [15]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [16]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [10]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A) OT5QQB5L IDH3A_HUMAN Decreases Expression [10]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [18]
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⏷ Show the Full List of 10 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
DD2 DC2DTWZ DD2 Investigative [1]
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References

1 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.
2 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: 7420).
3 Carfilzomib FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 The Zinc-Finger AN1-Type Domain 2a Gene Acts as a Regulator of Cell Survival in Human Melanoma: Role of E3-Ligase cIAP2. Mol Cancer Res. 2019 Dec;17(12):2444-2456. doi: 10.1158/1541-7786.MCR-19-0243. Epub 2019 Sep 20.
7 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
8 Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1. Am J Hematol. 2013 Apr;88(4):265-72.
9 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
10 Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
11 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
12 Suppression of BRCA1 sensitizes cells to proteasome inhibitors. Cell Death Dis. 2014 Dec 18;5(12):e1580. doi: 10.1038/cddis.2014.537.
13 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
14 Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35.
15 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
16 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
17 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
18 In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.