Details of the Drug Combination

General Information of Drug Combination (ID: DCWBO0J)

Drug Combination Name
Selinexor Lenalidomide
Indication
Disease Entry Status REF
Refractory Multiple Myeloma Phase 1 [1]
Component Drugs Selinexor   DMBD4K3 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 Selinexor
Disease Entry ICD 11 Status REF
Multiple myeloma 2A83 Approved [2]
Liposarcoma 2B59 Phase 3 [3]
Neuroendocrine cancer 2B72.1 Phase 3 [3]
Acute myeloid leukaemia 2A60 Phase 2 [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Diffuse large B-cell lymphoma 2A81 Phase 2 [4]
Recurrent glioblastoma 2A00.00 Phase 2 [3]
Solid tumour/cancer 2A00-2F9Z Phase 2 [6]
Selinexor Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Exportin-1 (XPO1) TTCJUR4 XPO1_HUMAN Inhibitor [10]
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Selinexor Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [11]
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Selinexor Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor protein p73 (TP73) OT0LUO47 P73_HUMAN Increases Expression [12]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [12]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [12]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [12]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [12]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Lenalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [7]
Advanced cancer 2A00-2F9Z Approved [7]
Complex regional pain syndrome type 1 N.A. Approved [7]
Hepatosplenic T-cell lymphoma N.A. Approved [7]
Large granular lymphocytic leukemia 2A90.1 Approved [7]
Leukemia N.A. Approved [7]
MALT lymphoma N.A. Approved [7]
Multiple myeloma 2A83 Approved [8]
Nodal marginal zone lymphoma 2A85.0 Approved [7]
Pain MG30-MG3Z Approved [7]
Plasma cell myeloma 2A83.1 Approved [7]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [7]
Prolymphocytic leukaemia 2A82.1 Approved [7]
Recurrent adult burkitt lymphoma 2A85.6 Approved [7]
Small intestine lymphoma N.A. Approved [7]
Splenic marginal zone lymphoma N.A. Approved [7]
Testicular lymphoma N.A. Approved [7]
Urinary bladder neoplasm N.A. Approved [7]
Waldenstrom macroglobulinemia 2A85.4 Approved [7]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [9]
Colon cancer 2B90.Z Investigative [7]
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 [13]
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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 [14]
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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 [15]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [16]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [16]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [16]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [15]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [15]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [16]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [16]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [16]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [16]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [17]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [18]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [19]
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⏷ Show the Full List of 13 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Multiple Myeloma DCO75M8 N. A. Phase 2 [20]
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References

1 ClinicalTrials.gov (NCT04519476) Selinexor Treatment for Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT04349098) Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection. U.S. National Institutes of Health.
6 ClinicalTrials.gov (NCT02025985) Phase II Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies. U.S. National Institutes of Health.
7 Lenalidomide FDA Label
8 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).
9 Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
10 Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014 August; 0: 62-73.
11 FDA label of Selinexor. The 2020 official website of the U.S. Food and Drug Administration.
12 The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
13 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
14 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
15 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.
16 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.
17 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.
18 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.
19 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.
20 ClinicalTrials.gov (NCT05820763) Selinexor and Lenalidomide for Consolidation and Maintenance Treatment in Multiple Myeloma Post-transplant