Details of the Drug Combination

General Information of Drug Combination (ID: DCON3LT)

Drug Combination Name
Gefitinib Letrozole
Indication
Disease Entry Status REF
Large cell lung carcinoma Investigative [1]
Component Drugs Gefitinib   DM15F0X Letrozole   DMH07Y3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H460
Zero Interaction Potency (ZIP) Score: 0.61
Bliss Independence Score: 7.5
Loewe Additivity Score: 0.2
LHighest Single Agent (HSA) Score: 3.42

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Gefitinib
Disease Entry ICD 11 Status REF
Colon adenocarcinoma N.A. Approved [2]
Glioblastoma 2A00 Approved [2]
Lung cancer 2C25.0 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Rectal adenocarcinoma 2B92 Approved [2]
Rectum mucinous adenocarcinoma N.A. Approved [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Head and neck cancer 2D42 Phase 3 [3]
Urethral cancer 2C93 Phase 2 [3]
Colon cancer 2B90.Z Investigative [2]
Colon mucinous adenocarcinoma N.A. Investigative [2]
Gefitinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [11]
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Gefitinib Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [14]
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Gefitinib 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]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [16]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [15]
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Gefitinib Interacts with 103 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 Increases ADR [17]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Response To Substance [18]
Sulfhydryl oxidase 1 (QSOX1) OT4ZPK4P QSOX1_HUMAN Increases Expression [19]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Decreases Expression [19]
Interferon alpha-inducible protein 6 (IFI6) OTWOOAM4 IFI6_HUMAN Decreases Expression [19]
Fibroblast growth factor 6 (FGF6) OTRJ679P FGF6_HUMAN Increases Expression [19]
Ski oncogene (SKI) OT4KJ8F6 SKI_HUMAN Increases Expression [19]
Erythropoietin receptor (EPOR) OTUIOEU3 EPOR_HUMAN Increases Expression [19]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [19]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [19]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [19]
Cytochrome P450 2F1 (CYP2F1) OTY3HJH1 CP2F1_HUMAN Decreases Expression [19]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Increases Expression [19]
Adenosine receptor A1 (ADORA1) OTI7X39E AA1R_HUMAN Decreases Expression [19]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [19]
DNA mismatch repair protein Mlh1 (MLH1) OTG5XDD8 MLH1_HUMAN Decreases Expression [19]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Increases Expression [19]
Epidermal growth factor receptor substrate 15 (EPS15) OT7NPP8U EPS15_HUMAN Increases Expression [19]
Neuronal pentraxin-2 (NPTX2) OT3SSJDP NPTX2_HUMAN Decreases Expression [19]
Leptin receptor (LEPR) OT9H7G0C LEPR_HUMAN Decreases Expression [19]
Neural retina-specific leucine zipper protein (NRL) OT65MFKQ NRL_HUMAN Decreases Expression [19]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2) OT3JPRCQ GBB2_HUMAN Decreases Expression [19]
Retinal guanylyl cyclase 1 (GUCY2D) OT81UJI0 GUC2D_HUMAN Decreases Expression [19]
Cell growth regulator with RING finger domain protein 1 (CGRRF1) OTLMNRCL CGRF1_HUMAN Increases Expression [19]
Dual specificity protein phosphatase 9 (DUSP9) OTZZWEQL DUS9_HUMAN Decreases Expression [19]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [20]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [21]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [21]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [21]
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Expression [22]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [23]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) OTVT4YA1 ATG7_HUMAN Increases Expression [24]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [25]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [7]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [26]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) OTRGGIFP DRB1_HUMAN Affects Expression [27]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Phosphorylation [28]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Phosphorylation [29]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA) OTZE5Q7R DOA_HUMAN Affects Expression [27]
Heat shock protein HSP 90-alpha (HSP90AA1) OTLG1WPK HS90A_HUMAN Increases Secretion [26]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Increases Phosphorylation [30]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Secretion [26]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [31]
Heat shock 70 kDa protein 1A (HSPA1A) OTKGIE76 HS71A_HUMAN Increases Secretion [26]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [32]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [7]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [24]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [33]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [18]
DnaJ homolog subfamily B member 1 (DNAJB1) OTCOSEVH DNJB1_HUMAN Increases Secretion [26]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Expression [34]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [34]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Increases Activity [26]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [18]
HLA class I histocompatibility antigen, alpha chain F (HLA-F) OT76CM19 HLAF_HUMAN Affects Expression [27]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [35]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [23]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [24]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Increases Expression [25]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [7]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [18]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Response To Substance [36]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [31]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Decreases Expression [22]
Caveolin-1 (CAV1) OTEZUR1L CAV1_HUMAN Increases Expression [34]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [37]
Kelch-like ECH-associated protein 1 (KEAP1) OTFHOD0C KEAP1_HUMAN Increases Expression [38]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [36]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [39]
MHC class I polypeptide-related sequence B (MICB) OTS2DVDW MICB_HUMAN Increases Expression [40]
MHC class I polypeptide-related sequence A (MICA) OTPEIEAR MICA_HUMAN Increases Expression [40]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Increases Expression [41]
Serine protease HTRA1 (HTRA1) OTR8ACBF HTRA1_HUMAN Increases Expression [42]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [27]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [24]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [43]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Decreases Response To Substance [44]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Response To Substance [45]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Affects Response To Substance [46]
Membrane-associated progesterone receptor component 1 (PGRMC1) OTBE6WAC PGRC1_HUMAN Decreases Response To Substance [47]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Response To Substance [48]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Affects Response To Substance [49]
RNA-binding protein 7 (RBM7) OTFIWTMF RBM7_HUMAN Affects Response To Substance [49]
Cell death regulator Aven (AVEN) OTGIN5YK AVEN_HUMAN Affects Response To Substance [49]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Response To Substance [50]
Phospholipase B-like 1 (PLBD1) OTHYEB4W PLBL1_HUMAN Affects Response To Substance [49]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Response To Substance [51]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Response To Substance [31]
Amphiregulin (AREG) OTJFOR67 AREG_HUMAN Decreases Response To Substance [49]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Affects Response To Substance [49]
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Decreases Response To Substance [51]
DNA excision repair protein ERCC-1 (ERCC1) OTNPYQHI ERCC1_HUMAN Affects Response To Substance [10]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Response To Substance [52]
Ceramide transfer protein (CERT1) OTNUCNHX CERT_HUMAN Affects Response To Substance [49]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Affects Response To Substance [53]
Oncostatin-M-specific receptor subunit beta (OSMR) OTORWHPL OSMR_HUMAN Affects Response To Substance [49]
Protransforming growth factor alpha (TGFA) OTPD1LL9 TGFA_HUMAN Decreases Response To Substance [54]
Dual specificity protein phosphatase 3 (DUSP3) OTPJX9B4 DUS3_HUMAN Affects Response To Substance [49]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Response To Substance [51]
Pericentrin (PCNT) OTW4Z65J PCNT_HUMAN Decreases Response To Substance [47]
Coronin-1C (CORO1C) OTXDF9T3 COR1C_HUMAN Affects Response To Substance [49]
Ribonucleoside-diphosphate reductase large subunit (RRM1) OTXGQOR9 RIR1_HUMAN Affects Response To Substance [10]
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⏷ Show the Full List of 103 DOT(s)
Indication(s) of Letrozole
Disease Entry ICD 11 Status REF
Estrogen-receptor positive breast cancer N.A. Approved [4]
Hormonally-responsive breast cancer 2C60-2C65 Approved [5]
Letrozole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [55]
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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 [56]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [57]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [58]
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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 [59]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [60]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Oxidation [60]
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [61]
Dickkopf-related protein 1 (DKK1) OTRDLUSP DKK1_HUMAN Increases Expression [62]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [63]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [63]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [64]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [62]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [65]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [66]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [66]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [67]
Leukemia inhibitory factor receptor (LIFR) OT36W9O5 LIFR_HUMAN Increases Expression [62]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [64]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [66]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Activity [68]
Fibroblast growth factor 22 (FGF22) OTVIX6J0 FGF22_HUMAN Increases Expression [62]
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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
Anaplastic large cell lymphoma DCTOG6H SR Investigative [1]
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References

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2 Gefitinib FDA Label
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4 Letrozole 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: 5209).
6 Synergistic antitumor effect of S-1 and the epidermal growth factor receptor inhibitor gefitinib in non-small cell lung cancer cell lines: role of gefitinib-induced down-regulation of thymidylate synthase. Mol Cancer Ther. 2008 Mar;7(3):599-606.
7 Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways. World J Gastrointest Oncol. 2022 Feb 15;14(2):450-477. doi: 10.4251/wjgo.v14.i2.450.
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20 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
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47 Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance. Toxicol Appl Pharmacol. 2015 Nov 1;288(3):359-73. doi: 10.1016/j.taap.2015.08.008. Epub 2015 Aug 20.
48 Induction of CYP1A1 increases gefitinib-induced oxidative stress and apoptosis in A549 cells. Toxicol In Vitro. 2017 Oct;44:36-43.
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