Details of the Drug Combination

General Information of Drug Combination (ID: DCXWCTK)

Drug Combination Name
Testosterone cypionate Gefitinib
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Testosterone cypionate   DMC1TEV Gefitinib   DM15F0X
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 12.26
Bliss Independence Score: 12.26
Loewe Additivity Score: 18.21
LHighest Single Agent (HSA) Score: 18.23

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Testosterone cypionate Interacts with 21 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [4]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [5]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [6]
Cytochrome P450 4B1 (CYP4B1) DEMF740 CP4B1_HUMAN Metabolism [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [8]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [12]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [13]
Cytochrome P450 3A43 (CYP3A43) DEO1IE3 CP343_HUMAN Metabolism [14]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [15]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Metabolism [16]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Metabolism [17]
Steroid 5-alpha-reductase 1 (SRD5A1) DEOG15F S5A1_HUMAN Metabolism [18]
Steroid 5-alpha-reductase 2 (SRD5A2) DEPTJ3D S5A2_HUMAN Metabolism [18]
Steroid 5-alpha-reductase 3 (SRD5A3) DEZGVDW PORED_HUMAN Metabolism [18]
Farnesol dehydrogenase (AKR1B15) DER0XCH AK1BF_HUMAN Metabolism [19]
Dehydrogenase/reductase retSDR3 (HSD17B14) DEGTB1K DHB14_HUMAN Metabolism [20]
Cytochrome P450 MEG (cyp106) DEZ1H4L CPXM_BACME Metabolism [21], [22]
Cytochrome P450 154C2 (cyp154) DEHDW40 A0A345AH95_STRSQ Metabolism [23], [24]
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⏷ Show the Full List of 21 DME(s)
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 [30]
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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 [31]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [32]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [33]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [33]
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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 [34]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [35]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [34]
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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 [36]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Response To Substance [37]
Sulfhydryl oxidase 1 (QSOX1) OT4ZPK4P QSOX1_HUMAN Increases Expression [38]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Decreases Expression [38]
Interferon alpha-inducible protein 6 (IFI6) OTWOOAM4 IFI6_HUMAN Decreases Expression [38]
Fibroblast growth factor 6 (FGF6) OTRJ679P FGF6_HUMAN Increases Expression [38]
Ski oncogene (SKI) OT4KJ8F6 SKI_HUMAN Increases Expression [38]
Erythropoietin receptor (EPOR) OTUIOEU3 EPOR_HUMAN Increases Expression [38]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [38]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [38]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [38]
Cytochrome P450 2F1 (CYP2F1) OTY3HJH1 CP2F1_HUMAN Decreases Expression [38]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Increases Expression [38]
Adenosine receptor A1 (ADORA1) OTI7X39E AA1R_HUMAN Decreases Expression [38]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [38]
DNA mismatch repair protein Mlh1 (MLH1) OTG5XDD8 MLH1_HUMAN Decreases Expression [38]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Increases Expression [38]
Epidermal growth factor receptor substrate 15 (EPS15) OT7NPP8U EPS15_HUMAN Increases Expression [38]
Neuronal pentraxin-2 (NPTX2) OT3SSJDP NPTX2_HUMAN Decreases Expression [38]
Leptin receptor (LEPR) OT9H7G0C LEPR_HUMAN Decreases Expression [38]
Neural retina-specific leucine zipper protein (NRL) OT65MFKQ NRL_HUMAN Decreases Expression [38]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2) OT3JPRCQ GBB2_HUMAN Decreases Expression [38]
Retinal guanylyl cyclase 1 (GUCY2D) OT81UJI0 GUC2D_HUMAN Decreases Expression [38]
Cell growth regulator with RING finger domain protein 1 (CGRRF1) OTLMNRCL CGRF1_HUMAN Increases Expression [38]
Dual specificity protein phosphatase 9 (DUSP9) OTZZWEQL DUS9_HUMAN Decreases Expression [38]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [39]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [40]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [40]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [40]
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Expression [41]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [42]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) OTVT4YA1 ATG7_HUMAN Increases Expression [43]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [44]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [26]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [45]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) OTRGGIFP DRB1_HUMAN Affects Expression [46]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Phosphorylation [47]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Phosphorylation [48]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA) OTZE5Q7R DOA_HUMAN Affects Expression [46]
Heat shock protein HSP 90-alpha (HSP90AA1) OTLG1WPK HS90A_HUMAN Increases Secretion [45]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Increases Phosphorylation [49]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Secretion [45]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [50]
Heat shock 70 kDa protein 1A (HSPA1A) OTKGIE76 HS71A_HUMAN Increases Secretion [45]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [51]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [26]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [26]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [43]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [52]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [37]
DnaJ homolog subfamily B member 1 (DNAJB1) OTCOSEVH DNJB1_HUMAN Increases Secretion [45]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Expression [53]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [53]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Increases Activity [45]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [37]
HLA class I histocompatibility antigen, alpha chain F (HLA-F) OT76CM19 HLAF_HUMAN Affects Expression [46]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [54]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [42]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [43]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Increases Expression [44]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [26]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [37]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Response To Substance [55]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [50]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Decreases Expression [41]
Caveolin-1 (CAV1) OTEZUR1L CAV1_HUMAN Increases Expression [53]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [56]
Kelch-like ECH-associated protein 1 (KEAP1) OTFHOD0C KEAP1_HUMAN Increases Expression [57]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [55]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [58]
MHC class I polypeptide-related sequence B (MICB) OTS2DVDW MICB_HUMAN Increases Expression [59]
MHC class I polypeptide-related sequence A (MICA) OTPEIEAR MICA_HUMAN Increases Expression [59]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Increases Expression [60]
Serine protease HTRA1 (HTRA1) OTR8ACBF HTRA1_HUMAN Increases Expression [61]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [46]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [43]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [62]
MARVEL domain-containing protein 1 (MARVELD1) OT5CPOJE MALD1_HUMAN Decreases Response To Substance [63]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Response To Substance [64]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Affects Response To Substance [65]
Membrane-associated progesterone receptor component 1 (PGRMC1) OTBE6WAC PGRC1_HUMAN Decreases Response To Substance [66]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Response To Substance [67]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Affects Response To Substance [68]
RNA-binding protein 7 (RBM7) OTFIWTMF RBM7_HUMAN Affects Response To Substance [68]
Cell death regulator Aven (AVEN) OTGIN5YK AVEN_HUMAN Affects Response To Substance [68]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Response To Substance [69]
Phospholipase B-like 1 (PLBD1) OTHYEB4W PLBL1_HUMAN Affects Response To Substance [68]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Response To Substance [70]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Response To Substance [50]
Amphiregulin (AREG) OTJFOR67 AREG_HUMAN Decreases Response To Substance [68]
Pleckstrin homology-like domain family A member 2 (PHLDA2) OTMV9DPP PHLA2_HUMAN Affects Response To Substance [68]
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Decreases Response To Substance [70]
DNA excision repair protein ERCC-1 (ERCC1) OTNPYQHI ERCC1_HUMAN Affects Response To Substance [29]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Response To Substance [71]
Ceramide transfer protein (CERT1) OTNUCNHX CERT_HUMAN Affects Response To Substance [68]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Affects Response To Substance [72]
Oncostatin-M-specific receptor subunit beta (OSMR) OTORWHPL OSMR_HUMAN Affects Response To Substance [68]
Protransforming growth factor alpha (TGFA) OTPD1LL9 TGFA_HUMAN Decreases Response To Substance [73]
Dual specificity protein phosphatase 3 (DUSP3) OTPJX9B4 DUS3_HUMAN Affects Response To Substance [68]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Response To Substance [70]
Pericentrin (PCNT) OTW4Z65J PCNT_HUMAN Decreases Response To Substance [66]
Coronin-1C (CORO1C) OTXDF9T3 COR1C_HUMAN Affects Response To Substance [68]
Ribonucleoside-diphosphate reductase large subunit (RRM1) OTXGQOR9 RIR1_HUMAN Affects Response To Substance [29]
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⏷ Show the Full List of 103 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Gefitinib 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: 4941).
4 Digging deeper into CYP3A testosterone metabolism: kinetic, regioselectivity, and stereoselectivity differences between CYP3A4/5 and CYP3A7. Drug Metab Dispos. 2017 Dec;45(12):1266-1275.
5 Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
6 Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
7 Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys. 1991 Oct;290(1):160-6.
8 In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44.
9 Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus. Res Commun Mol Pathol Pharmacol. 1998 Apr;100(1):15-28.
10 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
11 Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7.
12 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
13 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
14 cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol. 2001 Feb;59(2):386-92.
15 Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13.
16 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
17 Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis. 2005 Mar;26(3):621-9.
18 Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017 Oct 30;14(11).
19 Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates. J Biol Chem. 2015 Mar 6;290(10):6531-45.
20 Expression patterns of 17beta-hydroxysteroid dehydrogenase 14 in human tissues. Horm Metab Res. 2012 Dec;44(13):949-56.
21 acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
22 A Novel NADPH-dependent flavoprotein reductase from Bacillus megaterium acts as an efficient cytochrome P450 reductase. J Biotechnol. 2016 Aug 10;231:83-94.
23 Regio- and stereoselective hydroxylation of testosterone by a novel cytochrome P450 154C2 from Streptomyces avermitilis. Biochem Biophys Res Commun. 2020 Feb 5;522(2):355-361.
24 The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
25 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.
26 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.
27 EGFR inhibitors enhanced the susceptibility to NK cell-mediated lysis of lung cancer cells. J Immunother. 2011 May;34(4):372-81. doi: 10.1097/CJI.0b013e31821b724a.
28 Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo. Arch Toxicol. 2019 Jun;93(6):1555-1571. doi: 10.1007/s00204-019-02453-2. Epub 2019 Apr 16.
29 DNA repair gene polymorphisms and benefit from gefitinib in never-smokers with lung adenocarcinoma. Cancer. 2011 Jul 15;117(14):3201-8. doi: 10.1002/cncr.25863. Epub 2011 Jan 24.
30 Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
31 Gefitinib-phenytoin interaction is not correlated with the C-erythromycin breath test in healthy male volunteers. Br J Clin Pharmacol. 2009 Aug;68(2):226-37.
32 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
33 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
34 Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7.
35 Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Clin Pharmacokinet. 2005;44(10):1067-81.
36 Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst. 2006 Dec 6;98(23):1739-42.
37 Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival. Cancer Res. 2006 Jun 1;66(11):5542-8. doi: 10.1158/0008-5472.CAN-05-4620.
38 Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
39 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.
40 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
41 Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity. Anticancer Res. 2006 Sep-Oct;26(5A):3387-91.
42 Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
43 EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells. PLoS One. 2011;6(6):e18691. doi: 10.1371/journal.pone.0018691. Epub 2011 Jun 2.
44 ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Mol Cancer Ther. 2007 May;6(5):1579-87. doi: 10.1158/1535-7163.MCT-06-0814.
45 Reactive metabolite of gefitinib activates inflammasomes: implications for gefitinib-induced idiosyncratic reaction. J Toxicol Sci. 2020;45(11):673-680. doi: 10.2131/jts.45.673.
46 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
47 Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat. 2006 Mar;96(2):131-46. doi: 10.1007/s10549-005-9070-2. Epub 2005 Oct 27.
48 Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin Cancer Res. 2005 Oct 15;11(20):7480-9. doi: 10.1158/1078-0432.CCR-05-0328.
49 Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res. 2007 May 1;13(9):2795-803. doi: 10.1158/1078-0432.CCR-06-2077.
50 Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
51 Crosstalk between alveolar macrophages and alveolar epithelial cells/fibroblasts contributes to the pulmonary toxicity of gefitinib. Toxicol Lett. 2021 Mar 1;338:1-9. doi: 10.1016/j.toxlet.2020.11.011. Epub 2020 Nov 25.
52 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
53 Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
54 Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
55 The anti-cancer drug gefitinib accelerates Fas-mediated apoptosis by enhancing caspase-8 activation in cancer cells. J Toxicol Sci. 2019;44(6):435-440. doi: 10.2131/jts.44.435.
56 Autophagy Inhibition Overcomes the Antagonistic Effect Between Gefitinib and Cisplatin in Epidermal Growth Factor Receptor Mutant Non--Small-Cell Lung Cancer Cells. Clin Lung Cancer. 2015 Sep;16(5):e55-66. doi: 10.1016/j.cllc.2015.03.006. Epub 2015 Apr 2.
57 Nrf2 but not autophagy inhibition is associated with the survival of wild-type epidermal growth factor receptor non-small cell lung cancer cells. Toxicol Appl Pharmacol. 2016 Nov 1;310:140-149. doi: 10.1016/j.taap.2016.09.010. Epub 2016 Sep 14.
58 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
59 Susceptibility to natural killer cell-mediated lysis of colon cancer cells is enhanced by treatment with epidermal growth factor receptor inhibitors through UL16-binding protein-1 induction. Cancer Sci. 2012 Jan;103(1):7-16. doi: 10.1111/j.1349-7006.2011.02109.x. Epub 2011 Nov 15.
60 Combined tamoxifen and gefitinib in non-small cell lung cancer shows antiproliferative effects. Biomed Pharmacother. 2010 Feb;64(2):88-92. doi: 10.1016/j.biopha.2009.06.010. Epub 2009 Oct 23.
61 Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
62 A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
63 Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells. Oncotarget. 2016 Aug 9;7(32):52392-52403.
64 The K-Ras effector p38 MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulating EGFR transcription and EGFR dephosphorylation. J Biol Chem. 2017 Sep 8;292(36):15070-15079. doi: 10.1074/jbc.M117.779488. Epub 2017 Jul 24.
65 Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. Am J Respir Crit Care Med. 2011 Apr 15;183(8):1071-9. doi: 10.1164/rccm.201009-1440OC. Epub 2010 Oct 29.
66 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.
67 Induction of CYP1A1 increases gefitinib-induced oxidative stress and apoptosis in A549 cells. Toxicol In Vitro. 2017 Oct;44:36-43.
68 Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
69 The transcription factor FOXO3a is a crucial cellular target of gefitinib (Iressa) in breast cancer cells. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3169-79. doi: 10.1158/1535-7163.MCT-07-0507.
70 Aurora-A promotes gefitinib resistance via a NF-B signaling pathway in p53 knockdown lung cancer cells. Biochem Biophys Res Commun. 2011 Feb 11;405(2):168-72. doi: 10.1016/j.bbrc.2011.01.001. Epub 2011 Jan 7.
71 BIM induction of apoptosis triggered by EGFR-sensitive and resistance cell lines of non-small-cell lung cancer. Med Oncol. 2011 Jun;28(2):572-7. doi: 10.1007/s12032-010-9470-y. Epub 2010 Mar 17.
72 E3 ubiquitin ligase RNF180 reduces sensitivity of triple-negative breast cancer cells to Gefitinib by downregulating RAD51. Chem Biol Interact. 2022 Feb 25;354:109798. doi: 10.1016/j.cbi.2022.109798. Epub 2022 Jan 6.
73 Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. Cancer Res. 2005 Oct 15;65(20):9176-84. doi: 10.1158/0008-5472.CAN-05-1556.