General Information of Drug Combination (ID: DCPBH9K)

Drug Combination Name
Letrozole Busulfan
Indication
Disease Entry Status REF
Astrocytoma Investigative [1]
Component Drugs Letrozole   DMH07Y3 Busulfan   DMXYJ9C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: U251
Zero Interaction Potency (ZIP) Score: 4.47
Bliss Independence Score: 8.83
Loewe Additivity Score: 8.75
LHighest Single Agent (HSA) Score: 7.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Letrozole
Disease Entry ICD 11 Status REF
Estrogen-receptor positive breast cancer N.A. Approved [2]
Hormonally-responsive breast cancer 2C60-2C65 Approved [3]
Letrozole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [6]
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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 [7]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [8]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [9]
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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 [10]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [11]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Oxidation [11]
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [12]
Dickkopf-related protein 1 (DKK1) OTRDLUSP DKK1_HUMAN Increases Expression [13]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [14]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [14]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [15]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [13]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [16]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [17]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [18]
Leukemia inhibitory factor receptor (LIFR) OT36W9O5 LIFR_HUMAN Increases Expression [13]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [15]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [17]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Activity [19]
Fibroblast growth factor 22 (FGF22) OTVIX6J0 FGF22_HUMAN Increases Expression [13]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Busulfan
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [4]
Hematologic disease 3C0Z Approved [4]
Immunodeficiency 4A00-4A85 Approved [4]
Leukemia N.A. Approved [4]
Myeloproliferative syndrome 2A22 Approved [5]
Systemic lupus erythematosus 4A40.0 Approved [4]
Systemic sclerosis 4A42 Approved [4]
Neuroblastoma 2D11.2 Investigative [4]
Retinoblastoma 2D02.2 Investigative [4]
Busulfan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [21]
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Busulfan Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [22]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [23]
Glutathione S-transferase alpha-2 (GSTA2) DEH49YS GSTA2_HUMAN Metabolism [24]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [25]
Microsomal glutathione S-transferase 2 (MGST2) DE31KMQ MGST2_HUMAN Metabolism [26]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [25]
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⏷ Show the Full List of 6 DME(s)
Busulfan Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Affects Abundance [27]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Affects Abundance [27]
Microsomal glutathione S-transferase 2 (MGST2) OT4UGTDO MGST2_HUMAN Decreases Response To Substance [26]
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Response To Substance [28]
Serotransferrin (TF) OT41PEMS TRFE_HUMAN Increases Expression [29]
Inhibin beta A chain (INHBA) OTSP64PQ INHBA_HUMAN Increases Expression [29]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [29]
Antithrombin-III (SERPINC1) OTDFATG0 ANT3_HUMAN Affects Expression [30]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [31]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [31]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [20]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [32]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [31]
Thrombospondin-1 (THBS1) OT0ECWK3 TSP1_HUMAN Increases Expression [31]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [33]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Decreases Expression [31]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [33]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [20]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [20]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Activity [34]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Activity [34]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [20]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Expression [20]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [34]
Signal transducer and activator of transcription 1-alpha/beta (STAT1) OTLMBUZ6 STAT1_HUMAN Affects Expression [20]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [35]
Signal transducer and activator of transcription 2 (STAT2) OTO9G2RZ STAT2_HUMAN Decreases Expression [20]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [33]
Metal regulatory transcription factor 1 (MTF1) OTJWVLLF MTF1_HUMAN Decreases Expression [20]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [20]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [20]
Pseudouridylate synthase 7 homolog (PUS7) OTE5AQHJ PUS7_HUMAN Increases Expression [36]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [37]
Rho GDP-dissociation inhibitor 1 (ARHGDIA) OTEXWJDO GDIR1_HUMAN Affects Response To Substance [35]
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⏷ Show the Full List of 34 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCC7KQW DU-145 Investigative [1]
Adenocarcinoma DC24Y5I HCT-15 Investigative [1]
Amelanotic melanoma DC24BHY MDA-MB-435 Investigative [1]
Anaplastic large cell lymphoma DCTPM83 SR Investigative [1]
Clear cell renal cell carcinoma DCPHO3Y 786-0 Investigative [1]
Glioblastoma DCHDR52 SNB-75 Investigative [1]
Glioma DC3OQXC SF-268 Investigative [1]
Large cell lung carcinoma DCX9F86 NCI-H460 Investigative [1]
Lung adenocarcinoma DCCBWRL MDA-MB-231 Investigative [1]
Malignant melanoma DCW8A0O LOX IMVI Investigative [1]
Pleural epithelioid mesothelioma DCDGV8Q NCI-H226 Investigative [1]
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⏷ Show the Full List of 11 DrugCom(s)

References

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2 Letrozole FDA Label
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4 Busulfan FDA Label
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: 7136).
6 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
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19 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.
20 Direct transcriptomic comparison of xenobiotic metabolism and toxicity pathway induction of airway epithelium models at an air-liquid interface generated from induced pluripotent stem cells and primary bronchial epithelial cells. Cell Biol Toxicol. 2023 Feb;39(1):1-18. doi: 10.1007/s10565-022-09726-0. Epub 2022 May 31.
21 DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
22 Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy. 1998 Jan-Feb;18(1):84-112.
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29 Busulfan induces activin A expression in vitro and in vivo: a possible link to venous occlusive disease. Clin Pharmacol Ther. 2003 Sep;74(3):264-74.
30 Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol. 2005 May;84(5):321-30. doi: 10.1007/s00277-004-0982-4. Epub 2004 Dec 4.
31 Antineoplastic agent busulfan regulates a network of genes related to coagulation and fibrinolysis. Eur J Clin Pharmacol. 2012 Jun;68(6):923-35. doi: 10.1007/s00228-011-1209-y.
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33 Altered gene expression in busulfan-resistant human myeloid leukemia. Leuk Res. 2008 Nov;32(11):1684-97. doi: 10.1016/j.leukres.2008.01.016. Epub 2008 Mar 12.
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35 Reduced expression of Rho guanine nucleotide dissociation inhibitor-alpha modulates the cytotoxic effect of busulfan in HEK293 cells. Anticancer Drugs. 2007 Mar;18(3):333-40. doi: 10.1097/CAD.0b013e328011fd7f.
36 CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
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