Details of the Drug Combination

General Information of Drug Combination (ID: DCV60XW)

Drug Combination Name
Carfilzomib Auranofin
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Carfilzomib   DM48K0X Auranofin   DMWE2N4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: SU-DIPG-XIII
Zero Interaction Potency (ZIP) Score: 11.194
Bliss Independence Score: 15.204
Loewe Additivity Score: 0.665
LHighest Single Agent (HSA) Score: 0.584

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 Auranofin
Disease Entry ICD 11 Status REF
Inflammatory arthritis FA2Z Approved [5]
Auranofin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Steroid hormone receptor ERR (ESRR) TTP3UTW ERR1_HUMAN; ERR2_HUMAN; ERR3_HUMAN Modulator [13]
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Auranofin Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [14]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [14]
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Auranofin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Metallothionein-1A (MT1A) OTKBH52X MT1A_HUMAN Increases ADR [15]
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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 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: 6306).
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14 Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017 Oct 9;8(56):96062-96078.
15 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.