General Information of Drug Combination (ID: DCP5TTH)

Drug Combination Name
Letrozole Nilotinib
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Letrozole   DMH07Y3 Nilotinib   DM7HXWT
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HT29
Zero Interaction Potency (ZIP) Score: 3.42
Bliss Independence Score: 7.69
Loewe Additivity Score: 4.35
LHighest Single Agent (HSA) Score: 3.1

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 [5]
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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 [6]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [7]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [8]
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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 [9]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [10]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Oxidation [10]
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [11]
Dickkopf-related protein 1 (DKK1) OTRDLUSP DKK1_HUMAN Increases Expression [12]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [13]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [13]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [14]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [12]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [15]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [16]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [17]
Leukemia inhibitory factor receptor (LIFR) OT36W9O5 LIFR_HUMAN Increases Expression [12]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [14]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [16]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Activity [18]
Fibroblast growth factor 22 (FGF22) OTVIX6J0 FGF22_HUMAN Increases Expression [12]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Nilotinib
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [4]
Nilotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Modulator [22]
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Nilotinib Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [23]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [24]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [23]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [25]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [25]
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Nilotinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [26]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [27]
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Nilotinib Interacts with 35 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Response To Substance [28]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [30]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [30]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [30]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [30]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [20]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Phosphorylation [21]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [21]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Secretion [31]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [21]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [20]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [32]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [32]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [21]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [33]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [21]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [20]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Decreases Expression [21]
Histidine decarboxylase (HDC) OT4WA5YQ DCHS_HUMAN Decreases Expression [34]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [20]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [35]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [20]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [21]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [21]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [21]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [20]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [32]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Decreases Expression [20]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [20]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [20]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) OTWHN69S EDEM1_HUMAN Increases Expression [21]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [20]
Forkhead box protein C2 (FOXC2) OT83P1E0 FOXC2_HUMAN Decreases Expression [20]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [20]
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⏷ Show the Full List of 35 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Amelanotic melanoma DCQGXQY MDA-MB-435 Investigative [1]
Amelanotic melanoma DCKZTTG M14 Investigative [1]
Cutaneous melanoma DCG7T73 SK-MEL-5 Investigative [1]
Lung adenocarcinoma DC61CHF HOP-62 Investigative [1]
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References

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2 Letrozole FDA Label
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5 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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