General Information of Drug Combination (ID: DCL5LBF)

Drug Combination Name
Lenalidomide Letrozole
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Lenalidomide   DM6Q7U4 Letrozole   DMH07Y3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HCT116
Zero Interaction Potency (ZIP) Score: 1.31
Bliss Independence Score: 4.51
Loewe Additivity Score: 4.54
LHighest Single Agent (HSA) Score: 4.75

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 [7]
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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 [8]
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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 [9]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [10]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [10]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [10]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [9]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [9]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [10]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [10]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [10]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [10]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [11]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [12]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [13]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Letrozole
Disease Entry ICD 11 Status REF
Estrogen-receptor positive breast cancer N.A. Approved [5]
Hormonally-responsive breast cancer 2C60-2C65 Approved [6]
Letrozole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [14]
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Letrozole Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [16]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [17]
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Letrozole Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [18]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [19]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Oxidation [19]
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [20]
Dickkopf-related protein 1 (DKK1) OTRDLUSP DKK1_HUMAN Increases Expression [21]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [22]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [22]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [23]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [21]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [24]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [25]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [25]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [26]
Leukemia inhibitory factor receptor (LIFR) OT36W9O5 LIFR_HUMAN Increases Expression [21]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [23]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [25]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Activity [27]
Fibroblast growth factor 22 (FGF22) OTVIX6J0 FGF22_HUMAN Increases Expression [21]
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⏷ Show the Full List of 18 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Amelanotic melanoma DCKGHX7 MDA-MB-435 Investigative [1]
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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 Letrozole 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: 5209).
7 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
8 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
9 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.
10 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.
11 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.
12 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.
13 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.
14 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
15 Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro. Cancer Chemother Pharmacol. 2009 Oct;64(5):867-75.
16 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
17 Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer. Breast Cancer Res Treat. 2018 Nov;172(2):371-379.
18 Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
19 Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica. 2009 Nov;39(11):795-802. doi: 10.3109/00498250903171395.
20 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
21 Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome. Fertil Steril. 2011 Oct;96(4):1051-6. doi: 10.1016/j.fertnstert.2011.07.1092.
22 Aromatase inhibition, testosterone, and seizures. Epilepsy Behav. 2004 Apr;5(2):260-3. doi: 10.1016/j.yebeh.2003.12.001.
23 Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.
24 Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers. Toxicol Appl Pharmacol. 2018 Jan 1;338:182-190. doi: 10.1016/j.taap.2017.11.020. Epub 2017 Nov 24.
25 Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res. 2005 Jul 15;11(14):5319-28. doi: 10.1158/1078-0432.CCR-04-2402.
26 Synergistic activity of letrozole and sorafenib on breast cancer cells. Breast Cancer Res Treat. 2010 Nov;124(1):79-88. doi: 10.1007/s10549-009-0714-5. Epub 2010 Jan 7.
27 Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology. 2006 Nov 10;228(1):24-32. doi: 10.1016/j.tox.2006.08.007. Epub 2006 Aug 12.