Details of the Drug Combination

General Information of Drug Combination (ID: DCTXXK8)

Drug Combination Name
Carfilzomib Lenalidomide
Indication
Disease Entry Status REF
T-cell Lymphomas Phase 1 [1]
Component Drugs Carfilzomib   DM48K0X Lenalidomide   DM6Q7U4
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 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 [9]
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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 [10]
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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 [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [12]
Cytochrome c oxidase subunit 8A, mitochondrial (COX8A) OTU0NR39 COX8A_HUMAN Decreases Expression [12]
Basigin (BSG) OTD0CVEC BASI_HUMAN Decreases Expression [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [13]
C-X-C chemokine receptor type 4 (CXCR4) OTUFSBX2 CXCR4_HUMAN Decreases Expression [13]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [12]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Response To Substance [14]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Lenalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [5]
Advanced cancer 2A00-2F9Z Approved [5]
Complex regional pain syndrome type 1 N.A. Approved [5]
Hepatosplenic T-cell lymphoma N.A. Approved [5]
Large granular lymphocytic leukemia 2A90.1 Approved [5]
Leukemia N.A. Approved [5]
MALT lymphoma N.A. Approved [5]
Multiple myeloma 2A83 Approved [6]
Nodal marginal zone lymphoma 2A85.0 Approved [5]
Pain MG30-MG3Z Approved [5]
Plasma cell myeloma 2A83.1 Approved [5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [5]
Prolymphocytic leukaemia 2A82.1 Approved [5]
Recurrent adult burkitt lymphoma 2A85.6 Approved [5]
Small intestine lymphoma N.A. Approved [5]
Splenic marginal zone lymphoma N.A. Approved [5]
Testicular lymphoma N.A. Approved [5]
Urinary bladder neoplasm N.A. Approved [5]
Waldenstrom macroglobulinemia 2A85.4 Approved [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [7]
Colon cancer 2B90.Z Investigative [5]
Lenalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) TTF8CQI TNFA_HUMAN Inhibitor [15]
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Lenalidomide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]
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Lenalidomide Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Affects Expression [17]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [18]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [18]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [18]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [17]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [17]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [18]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [18]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [18]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [18]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [19]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [20]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [21]
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⏷ Show the Full List of 13 DOT(s)

References

1 ClinicalTrials.gov (NCT02341014) Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas
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 Lenalidomide FDA Label
6 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: 7331).
7 Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
8 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.
9 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
10 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.
11 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.
12 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.
13 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
14 Suppression of BRCA1 sensitizes cells to proteasome inhibitors. Cell Death Dis. 2014 Dec 18;5(12):e1580. doi: 10.1038/cddis.2014.537.
15 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
16 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
17 Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
18 Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005 Apr 15;105(8):3286-94. doi: 10.1182/blood-2004-06-2101. Epub 2004 Dec 23.
19 Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014 Sep;21(9):803-9. doi: 10.1038/nsmb.2874. Epub 2014 Aug 10.
20 Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
21 A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.