General Information of Drug Combination (ID: DCNW8WZ)

Drug Combination Name
Raloxifene Lenalidomide
Indication
Disease Entry Status REF
High grade ovarian serous adenocarcinoma Investigative [1]
Component Drugs Raloxifene   DMDKF3M Lenalidomide   DM6Q7U4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR-8
Zero Interaction Potency (ZIP) Score: 1.76
Bliss Independence Score: 3.45
Loewe Additivity Score: 4.46
LHighest Single Agent (HSA) Score: 3.44

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Raloxifene
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Approved [2]
Raloxifene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Modulator [6]
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Raloxifene Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Raloxifene Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [10]
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Indication(s) of Lenalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [3]
Advanced cancer 2A00-2F9Z Approved [3]
Complex regional pain syndrome type 1 N.A. Approved [3]
Hepatosplenic T-cell lymphoma N.A. Approved [3]
Large granular lymphocytic leukemia 2A90.1 Approved [3]
Leukemia N.A. Approved [3]
MALT lymphoma N.A. Approved [3]
Multiple myeloma 2A83 Approved [4]
Nodal marginal zone lymphoma 2A85.0 Approved [3]
Pain MG30-MG3Z Approved [3]
Plasma cell myeloma 2A83.1 Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [3]
Prolymphocytic leukaemia 2A82.1 Approved [3]
Recurrent adult burkitt lymphoma 2A85.6 Approved [3]
Small intestine lymphoma N.A. Approved [3]
Splenic marginal zone lymphoma N.A. Approved [3]
Testicular lymphoma N.A. Approved [3]
Urinary bladder neoplasm N.A. Approved [3]
Waldenstrom macroglobulinemia 2A85.4 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [5]
Colon cancer 2B90.Z Investigative [3]
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 [11]
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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 [12]
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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 [13]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [14]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [14]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [14]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [13]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [13]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [14]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [14]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [14]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [14]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [15]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [16]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [17]
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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
Adenocarcinoma DCMGRIM HCT116 Investigative [1]
Cutaneous melanoma DCOXF31 SK-MEL-5 Investigative [1]
Prostate carcinoma DCMJ3QO PC-3 Investigative [1]
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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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Lenalidomide FDA Label
4 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).
5 Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
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. (Target id: 620).
7 Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
8 The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
9 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
10 Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
11 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
12 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
13 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.
14 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.
15 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.
16 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.
17 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.