General Information of Drug Combination (ID: DCE2F51)

Drug Combination Name
Lenalidomide Plicamycin
Indication
Disease Entry Status REF
Plasma cell myeloma Investigative [1]
Component Drugs Lenalidomide   DM6Q7U4 Plicamycin   DM7C8YV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: RPMI-8226
Zero Interaction Potency (ZIP) Score: 1.38
Bliss Independence Score: 10.66
Loewe Additivity Score: 7.86
LHighest Single Agent (HSA) Score: 7.89

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lenalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [2]
Advanced cancer 2A00-2F9Z Approved [2]
Complex regional pain syndrome type 1 N.A. Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [2]
Large granular lymphocytic leukemia 2A90.1 Approved [2]
Leukemia N.A. Approved [2]
MALT lymphoma N.A. Approved [2]
Multiple myeloma 2A83 Approved [3]
Nodal marginal zone lymphoma 2A85.0 Approved [2]
Pain MG30-MG3Z Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [2]
Prolymphocytic leukaemia 2A82.1 Approved [2]
Recurrent adult burkitt lymphoma 2A85.6 Approved [2]
Small intestine lymphoma N.A. Approved [2]
Splenic marginal zone lymphoma N.A. Approved [2]
Testicular lymphoma N.A. Approved [2]
Urinary bladder neoplasm N.A. Approved [2]
Waldenstrom macroglobulinemia 2A85.4 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Colon cancer 2B90.Z Investigative [2]
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 [8]
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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 [9]
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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 [10]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [11]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [11]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [11]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [10]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [10]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [11]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [11]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [11]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [11]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [12]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [13]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [14]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [5]
Testicular cancer 2C80 Approved [5]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [6]
Lung cancer 2C25.0 Investigative [7]
Ovarian cancer 2C73 Investigative [7]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [16]
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Plicamycin Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [17]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [18]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [18]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [18]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [19]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [19]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [20]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [15]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [21]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [22]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [23]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [15]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [24]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [21]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [25]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [26]
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⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCSRLWD HL-60(TB) Investigative [1]
Glioma DC4GZ3L SF-295 Investigative [1]
Breast adenocarcinoma DCGJB2R MDA-MB-468 Investigative [27]
Carcinoma DCOU517 RXF 393 Investigative [27]
Invasive ductal carcinoma DC99LBU BT-549 Investigative [27]
Invasive ductal carcinoma DCPEW12 HS 578T Investigative [27]
Adenocarcinoma DCDGNVH HCC-2998 Investigative [28]
Cutaneous melanoma DCTNZPD SK-MEL-5 Investigative [28]
Cutaneous melanoma DCSKR1I SK-MEL-28 Investigative [28]
High grade ovarian serous adenocarcinoma DCJVBK2 OVCAR-8 Investigative [28]
Lung adenocarcinoma DC4P8S4 NCI-H522 Investigative [28]
Melanoma DC3HPS3 SK-MEL-2 Investigative [28]
Melanoma DCNQ56B MALME-3M Investigative [28]
Melanoma DCTOJTU UACC-257 Investigative [28]
Minimally invasive lung adenocarcinoma DCRDTDB NCI-H322M Investigative [28]
Pleural epithelioid mesothelioma DCKJFE4 NCI-H226 Investigative [28]
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⏷ Show the Full List of 16 DrugCom(s)

References

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2 Lenalidomide FDA Label
3 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).
4 Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
7 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
8 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
9 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
10 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.
11 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.
12 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.
13 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.
14 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.
15 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
16 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
17 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
18 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
19 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
20 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
21 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
22 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
23 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
24 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
25 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
26 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
27 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
28 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.