General Information of Drug Combination (ID: DC1K15G)

Drug Combination Name
Lenalidomide Romidepsin
Indication
Disease Entry Status REF
Prostate carcinoma Investigative [1]
Component Drugs Lenalidomide   DM6Q7U4 Romidepsin   DMT5GNL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: PC-3
Zero Interaction Potency (ZIP) Score: 0.99
Bliss Independence Score: 3.15
Loewe Additivity Score: 4.49
LHighest Single Agent (HSA) Score: 5.07

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 Romidepsin
Disease Entry ICD 11 Status REF
Cutaneous T-cell lymphoma 2B01 Approved [5]
Gastrin-producing neuroendocrine tumor N.A. Approved [6]
Glucagonoma N.A. Approved [6]
Insulinoma 2C10.1 Approved [6]
Lung carcinoid tumor N.A. Approved [6]
Melanoma 2C30 Approved [6]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [6]
Primary cutaneous T-cell lymphoma N.A. Approved [6]
Urethral cancer 2C93 Approved [6]
Peripheral T-cell lymphoma 2A90.C Phase 3 [7]
Renal cell carcinoma 2C90 Phase 3 [5]
Romidepsin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histone deacetylase 1 (HDAC1) TT6R7JZ HDAC1_HUMAN Inhibitor [17]
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Romidepsin Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [18]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [18]
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Romidepsin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [19]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [20]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [21]
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Romidepsin Interacts with 41 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [22]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Expression [23]
E3 SUMO-protein ligase CBX4 (CBX4) OT4XVRRF CBX4_HUMAN Increases Expression [24]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [25]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [26]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [27]
Serine/threonine-protein kinase 17B (STK17B) OT4NYNO8 ST17B_HUMAN Increases Expression [24]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [28]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Expression [28]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [28]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [28]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [29]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Increases Expression [24]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [28]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [16]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [24]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [29]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [28]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [29]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [16]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [16]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [30]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Phosphorylation [16]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [24]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [31]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [28]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [29]
Friend leukemia integration 1 transcription factor (FLI1) OT0EV3LX FLI1_HUMAN Decreases Expression [32]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Decreases Expression [32]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [16]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [30]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [24]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1) OT6VY3A3 SPTN1_HUMAN Increases Expression [24]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Expression [33]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [30]
Histone H3.1t (H3-4) OTY6ITYF H31T_HUMAN Increases Acetylation [33]
Sodium/iodide cotransporter (SLC5A5) OTU7E9G7 SC5A5_HUMAN Increases Expression [34]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) OT53LJGW M3K3_HUMAN Increases Expression [24]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Affects Metabolism [35]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [36]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Response To Substance [29]
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⏷ Show the Full List of 41 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult Nasal Type Extranodal NK/T-cell Lymphoma DC9Q0YM N. A. Phase 2 [37]
Multiple Myeloma DCVYV4M N. A. Phase 1 [38]
Invasive ductal carcinoma DC1A03H BT-549 Investigative [39]
Adenocarcinoma DCUDZCU A549 Investigative [1]
Lung adenocarcinoma DC0RN0G EKVX Investigative [1]
Lung adenocarcinoma DC8KPAK NCI-H522 Investigative [1]
Malignant melanoma DCEPNMK LOX IMVI Investigative [1]
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⏷ Show the Full List of 7 DrugCom(s)

References

1 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.
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 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: 7006).
6 Romidepsin FDA Label
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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 Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil Steril. 2011 Apr;95(5):1579-83. doi: 10.1016/j.fertnstert.2010.12.058. Epub 2011 Feb 4.
16 Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3. Arch Toxicol. 2022 Jan;96(1):177-193. doi: 10.1007/s00204-021-03174-1. Epub 2021 Oct 19.
17 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
18 Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
19 A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011 May;13(5):509-16.
20 Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
21 FDA Label of Romidepsin. The 2020 official website of the U.S. Food and Drug Administration.
22 Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines. J Pharmacol Exp Ther. 2005 Jul;314(1):467-75. doi: 10.1124/jpet.105.083956. Epub 2005 Apr 15.
23 Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol Cell Biol. 2006 Nov;26(22):8572-85.
24 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochem Biophys Res Commun. 2006 Dec 15;351(2):455-61. doi: 10.1016/j.bbrc.2006.10.055. Epub 2006 Oct 18.
25 Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res. 2006 Jul 15;66(14):7317-25. doi: 10.1158/0008-5472.CAN-06-0680.
26 Histone deacetylase inhibitors FK228, N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino- methyl]benzamide and m-carboxycinnamic acid bis-hydroxamide augment radiation-induced cell death in gastrointestinal adenocarcinoma cells. Int J Cancer. 2004 Jun 10;110(2):301-8. doi: 10.1002/ijc.20117.
27 A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45beta expression in hepatocellular carcinoma cells. Anticancer Res. 2007 Nov-Dec;27(6B):3783-9.
28 Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells. Clin Cancer Res. 2004 Mar 1;10(5):1813-25. doi: 10.1158/1078-0432.ccr-0901-3.
29 Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res. 2008 Jan 15;14(2):549-58. doi: 10.1158/1078-0432.CCR-07-1934.
30 Blocking downstream signaling pathways in the context of HDAC inhibition promotes apoptosis preferentially in cells harboring mutant Ras. Oncotarget. 2016 Oct 25;7(43):69804-69815. doi: 10.18632/oncotarget.12001.
31 Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells. Blood. 2006 Feb 15;107(4):1546-54. doi: 10.1182/blood-2004-10-4126. Epub 2005 Oct 13.
32 Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors. Int J Cancer. 2005 Sep 20;116(5):784-92. doi: 10.1002/ijc.21069.
33 Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. J Urol. 2005 Aug;174(2):747-52. doi: 10.1097/01.ju.0000164723.20555.e6.
34 Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer. 2006 Sep;13(3):797-826. doi: 10.1677/erc.1.01143.
35 Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. Biol Pharm Bull. 2005 Jan;28(1):124-9.
36 Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells. Int J Cancer. 2006 Jan 1;118(1):90-7. doi: 10.1002/ijc.21297.
37 ClinicalTrials.gov (NCT02232516) Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma
38 ClinicalTrials.gov (NCT01755975) Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma
39 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.