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Drug Details
01. General Information
Name Gefitinib
PubChem CID 123631
Molecular Weight 446.9g/mol
Synonyms

Gefitinib, 184475-35-2, Iressa, ZD1839, Irressat, N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine, gefitinib (zd1839), ZD 1839, ZD-1839, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine, gefitinibum, CCRIS 9011, UNII-S65743JHBS, Gefitinib (GMP), NSC-759856, N-(3-Chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine, S65743JHBS, DTXSID8041034, CHEBI:49668, 4-(3'-Chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine, MFCD04307832, CHEMBL939, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine, DTXCID6021034, NSC715055, NSC 759856, Gefitinib [USAN], NCGC00159455-02, GEFITINIB (MART.), GEFITINIB [MART.], N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine, 3-Chloro-4-Fluoro-N-[(4z)-7-Methoxy-6-(3-Morpholin-4-Ylpropoxy)quinazolin-4(1h)-Ylidene]aniline, C22H24ClFN4O3, GEFITINIB (EP MONOGRAPH), GEFITINIB [EP MONOGRAPH], 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-, Iressa(TM), IRE, Iressa (TN), CAS-184475-35-2, SR-00000000262, Gefitinib (JAN/USAN/INN), Gefitinib [USAN:INN:BAN], Gefitini; Iressa, 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine, Iressa (AstraZeneca), nchembio866-comp14, Kinome_3321, Kinome_3322, GEFITINIB [INN], GEFITINIB [JAN], GEFITINIB [MI], GEFITINIB [VANDF], GEFITINIB [WHO-DD], SCHEMBL7866, Gefitinib,ZD-1839,Iressa, GEFITINIB [EMA EPAR], KBioSS_002241, MLS003899193, CU-00000000396-1, BDBM5447, cid_123631, GTPL4941, GEFITINIB [ORANGE BOOK], Gefitinib, >=98% (HPLC), L01XE02, BCPP000221, HMS2089B19, HMS3244M21, HMS3244M22, HMS3244N21, HMS3295A21, HMS3413H08, HMS3654A07, HMS3677H08, HMS3714A05, HMS3748E17, Pharmakon1600-01502274, BCP01365, Tox21_111683, HY-50895G, NSC759856, NSC800105, s1025, STK621310, AKOS000280752, Tox21_111683_1, AB20814, AC-1556, BCP9000718, CCG-220642, CS-0124, DB00317, KS-1204, NSC-715055, NSC-800105, 4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxy-6-(3-morpholinopropoxy)quinazoline, 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-4-morpholin)propoxy)-, 6-(3-morpholinopropoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine, NCGC00159455-03, NCGC00159455-04, NCGC00159455-05, NCGC00159455-06, NCGC00159455-08, NCGC00159455-09, NCGC00159455-14, BCB03_000781, BG164498, HY-50895, SMR002204119, SY002154, AM20090619, CS-0622782, FT-0602325, G0546, NS00006312, SW199108-4, D01977, EN300-123024, G-4408, K00240, AB01273954-01, AB01273954-02, AB01273954-03, AB01273954_04, A812870, Q417824, Q-201149, SR-00000000262-2, SR-00000000262-3, Gefitinib, EuropePharmacopoeia (EP) Reference Standard, Z1546610485, 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)-quinazoline, Gefitinib for system suitability, EuropePharmacopoeia (EP) Reference Standard, (3-CHLORO-4-FLUORO-PHENYL)-[7-METHOXY-6-(3-MORPHOLIN-4-YL-PROPOXY)-QUINAZOLIN-4-YL]-AMINE
Drug Type Small molecule
Formula C₂₂H₂₄ClFN₄O₃
SMILES COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
InChI 1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)
InChIKey XGALLCVXEZPNRQ-UHFFFAOYSA-N
CAS Number 184475-35-2
ChEMBL ID CHEMBL939
ChEBI ID CHEBI:49668
TTD ID D09XZB
Drug Bank ID DB00317
KEGG ID D01977
Toxicity Organism Test Type Route(Dose)
rat LD50 intraperitoneal(165 mg/kg)
mouse LD50 intraperitoneal(254 mg/kg)
rat LD50 oral(322 mg/kg)
Structure 2D-img
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2D MOL 3D MOL
02. Combinatorial Therapeutic Effect(s)
Synergistic Effect
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Enhancing Drug Efficacy
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Combination Pair ID: 918
Ref_1
Pair Name Zerumbone, Gefitinib
Partner Name Zerumbone
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression EGFR hsa1956
Down-regulation Expression GPX4 hsa2879
Down-regulation Expression KDR hsa3791
Down-regulation Expression SLC7A11 hsa23657
Down-regulation Phosphorylation STAT3 hsa6774
Up-regulation Expression TP53 hsa7157
Up-regulation Expression VEGFA hsa7422
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H460 Lung large cell carcinoma Homo sapiens (Human) CVCL_0459
In Vivo Model The mice were injected with 1×10⁷ cell/mL A549 cells (0.2ml/mice) into the left axilla.
Result Our study suggested that zerumbone combined with gefitinib could effectively inhibit lung cancer for multi-model therapies, including the inhibition of tumor growth, angiogenesis, induce cell apoptosis, and ferroptosis.
Combination Pair ID: 548
Ref_2
Pair Name Sulforaphane, Gefitinib
Partner Name Sulforaphane
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Up-regulation Expression CLDN1 hsa9076
Down-regulation Phosphorylation EGFR hsa1956
Down-regulation Phosphorylation MAPK1 hsa5594
Down-regulation Expression VIM hsa7431
In Vitro Model PC-9 Lung adenocarcinoma Homo sapiens (Human) CVCL_B260
Result SFN overcame T790M-mediated gefitinib resistance in vitro through EMT. Thus, a combination of gefitinib and SFN may be a beneficial treatment strategy for lung cancer patients with acquired resistance due to T790M mutation.
Combination Pair ID: 797
Ref_3
Pair Name Solamargine, Gefitinib
Partner Name Solamargine
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Gene Regulation Up-regulation Expression IGFBP1 hsa3484
Up-regulation Expression SP1 hsa6667
Result We confirmed that SM significantly enhanced the anticancer effect of EGFR-TKIs by regulating the MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway. This study unravels a novel mechanism and suggests a new potential NSCLC-associated therapy.
Combination Pair ID: 461
Ref_4
Pair Name Shogaol, Gefitinib
Partner Name Shogaol
Disease Info [ICD-11: 2C73] Ovarian Cancer Investigative
Biological Phenomena Induction-->Endoplasmic reticulum stress
Gene Regulation Up-regulation Expression ATF4 hsa468
Up-regulation Cleavage CASP3 hsa836
Up-regulation Cleavage CASP8 hsa841
Up-regulation Cleavage CASP9 hsa842
Up-regulation Expression CD63 hsa967
Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Up-regulation Expression DDIT3 hsa1649
Up-regulation Phosphorylation EIF2AK3 hsa9451
Up-regulation Phosphorylation EIF2S1 hsa1965
Up-regulation Expression HSPA5 hsa3309
Up-regulation Expression NOX4 hsa50507
Down-regulation Expression SNAI1 hsa6615
Down-regulation Expression SNAI2 hsa6591
Up-regulation Expression TNFRSF10B hsa8795
Down-regulation Expression VIM hsa7431
In Vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens (Human) CVCL_0134
OVCAR-3 High grade ovarian serous adenocarcinoma Homo sapiens (Human) CVCL_0465
Caov-3 High grade ovarian serous adenocarcinoma Homo sapiens (Human) CVCL_0201
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens (Human) CVCL_0532
In Vivo Model For the mice xenograft experiment, mice, aged six weeks, were inoculated with an A2780 human ovarian cancer cell line by subcutaneously (sc) implanting 1×10⁷ cultured cells into the right thigh.
Result Our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer.
Combination Pair ID: 286
Ref_5
Pair Name Shikonin, Gefitinib
Partner Name Shikonin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Gene Regulation Down-regulation Expression CCND1 hsa595
Down-regulation Expression PKM hsa5315
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model Mice were injected with A549 (1×10⁷) in the dorsal area.
Result These results provide a promising therapeutic approach for the treatment of wild-type EGFR non-small cell lung cancer.
Combination Pair ID: 227
Ref_6
Pair Name Saikosaponin D, Gefitinib
Partner Name Saikosaponin D
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression BCL2 hsa596
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens (Human) CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens (Human) CVCL_B260
HCC827-GR-high1 Lung adenocarcinoma Homo sapiens (Human) CVCL_S703
Hep-G2 Hepatoblastoma Homo sapiens (Human) CVCL_0027
In Vivo Model Mice were intraperitoneally injected with HCC827/GR (1×10⁷) cells in the dorsal region.
Result These results indicated that the combination of SSD with gefitinib had an increased antitumor effect in NSCLC cells and that the molecular mechanisms were associated with the inhibition of STAT3/Bcl-2 signaling pathway. Our findings suggest a promising approach for the treatment of NSCLC patients with EGFR-TKI resistance.
Combination Pair ID: 605
Ref_7
Pair Name Phenethyl isothiocyanate, Gefitinib
Partner Name Phenethyl isothiocyanate
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Endoplasmic reticulum stress
Gene Regulation Up-regulation Cleavage CASP8 hsa841
Down-regulation Expression DDIT3 hsa1649
Up-regulation Phosphorylation EIF2AK3 hsa9451
Up-regulation Phosphorylation EIF2S1 hsa1965
Down-regulation Expression MCL1 hsa4170
Up-regulation Cleavage PARP1 hsa142
Down-regulation Expression PMAIP1 hsa5366
In Vitro Model NCI-H1299 Lung large cell carcinoma Homo sapiens (Human) CVCL_0060
SK-MES-1 Lung squamous cell carcinoma Homo sapiens (Human) CVCL_0630
In Vivo Model NCI‐H1299 cells were subcutaneouslyinjected into the flank of mice.Mice were randomly divided into four groups (four mice pergroup) when the tumor size reached approximately 10 mm3.
Result We explored the prospect of PEITC in improving the efficacy of targeted drug therapy and demonstrated the synergistic effects and underlined mechanisms of PEITC combined with Gefitinib in NSCLC cells treatment. This study provided useful information for developing novel therapy strategies by combination treatment of PEITC with targeted drugs.
Combination Pair ID: 850
Ref_8
Pair Name Luteolin, Gefitinib
Partner Name Luteolin
Disease Info [ICD-11: 2C82] Prostate cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
In Vitro Model PC-3 Prostate carcinoma Homo sapiens (Human) CVCL_0035
Result Luteolin and gefitinib regulate CCP gene expression through a common mechanism involving EGFR-associated tyrosine kinase
Combination Pair ID: 69
Ref_9
Pair Name Kaempferol, Gefitinib
Partner Name Kaempferol
Disease Info [ICD-11: 2F7Z] Glioma Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation Down-regulation Phosphorylation EGFR hsa1956
Down-regulation Phosphorylation SRC hsa6714
Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model U-251MG Astrocytoma Homo sapiens (Human) CVCL_0021
In Vivo Model U251 cells at a count of 1×10⁷cells per 200 μl weresubcutaneously injected into the right armpit and mice wererandomly divided into six groups of six each.
Result Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway
Combination Pair ID: 468
Ref_10
Pair Name Gossypol, Gefitinib
Partner Name Gossypol
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Cleavage CASP3 hsa836
Down-regulation Phosphorylation EGFR hsa1956
Down-regulation Phosphorylation MAPK1 hsa5594
In Vitro Model PC-9-GR-high Lung adenocarcinoma Homo sapiens (Human) CVCL_S706
NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
Result AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations.
Combination Pair ID: 167
Ref_11
Pair Name Dihydroartemisinin, Gefitinib
Partner Name Dihydroartemisinin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Up-regulation Expression ROS1 hsa6098
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
Result Dihydroartemisinin enhances gefitinib cytotoxicity against lung adenocarcinoma cells by inducing ROS-dependent apoptosis and ferroptosis
Combination Pair ID: 89
Ref_12
Pair Name Daidzein, Gefitinib
Partner Name Daidzein
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation Down-regulation Expression AKT1 hsa207
Down-regulation Expression EGFR hsa1956
Up-regulation Activity JUN hsa3725
Up-regulation Activity MAP3K5 hsa4217
Down-regulation Expression MAPK1 hsa5594
Up-regulation Activity MAPK8 hsa5599
Up-regulation Activity ROS1 hsa6098
Down-regulation Expression SOAT1 hsa6646
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model 4×10⁶ A549 cancer cells in Matrigel serum free medium (BD Biosciences) suspension were subcutaneously injected into 8-week-old male NU/NU mice hind legs.
Result Daidzein Synergizes with Gefitinib to Induce ROS/JNK/c-Jun Activation and Inhibit EGFR-STAT/AKT/ERK Pathways to enhance Lung Adenocarcinoma cells chemosensitivity
Combination Pair ID: 731
Ref_13
Pair Name Cryptotanshinone, Gefitinib
Partner Name Cryptotanshinone
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Gene Regulation Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression GABPA hsa2551
Down-regulation Expression TK1 hsa7083
In Vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens (Human) CVCL_0060
In Vivo Model H1975 human lung cancer cells (5×10⁷ in 1 ml) or PC9/GR human lung cancer cells (3×10⁷ in 1 ml) were injected subcutaneously into the right flank of athymic BALB/c nude mice (3-4 weeks old).
Result These findings indicated the role of TKT in lung cancer progression and may provide novel therapeutic strategies to overcome resistance to gefitinib. Furthermore, CTS may serve as a new candidate in adjuvant treatment of advanced lung cancer.
Combination Pair ID: 708
Ref_14
Pair Name Beta-Elemene, Gefitinib
Partner Name Beta-Elemene
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Up-regulation Expression HES1 hsa3280
Up-regulation Expression MYC hsa4609
Up-regulation Expression NOTCH1 hsa4851
Up-regulation Expression SHH hsa6469
Down-regulation Expression SNAI1 hsa6615
Up-regulation Expression SOX2 hsa6657
Down-regulation Expression TWIST1 hsa7291
Down-regulation Expression VIM hsa7431
Down-regulation Expression ZEB1 hsa6935
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens (Human) CVCL_0060
Result The findings may have potential implications for treating aggressive and resistant lung cancers.
Combination Pair ID: 77
Ref_15
Pair Name Apigenin, Gefitinib
Partner Name Apigenin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Expression EGFR hsa1956
Down-regulation Expression HIF1A hsa3091
Down-regulation Expression MYC hsa4609
Down-regulation Activity PRKAA1 hsa5562
Down-regulation Expression SLC16A1 hsa6566
In Vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
Result Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells
Combination Pair ID: 303
Ref_16
Pair Name Aloe emodin, Gefitinib
Partner Name Aloe emodin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Down-regulation Expression AKT1 hsa207
Down-regulation Expression PIK3CA hsa5290
Down-regulation Expression SLC22A3 hsa6581
In Vitro Model PC-9 Lung adenocarcinoma Homo sapiens (Human) CVCL_B260
PC-9-GR-high Lung adenocarcinoma Homo sapiens (Human) CVCL_S706
In Vivo Model After acclimated for one week, subcutaneous inoculation of 1×10⁷ PC9-GR cells was executed into the right flank of the animals (n = 4 in each group) to develop xenograft models.
Result AE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.
Reversing Drug Resistance
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Combination Pair ID: 153
Ref_17
Pair Name Triptolide, Gefitinib
Partner Name Triptolide
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Epithelial-mesenchymal transition
Gene Regulation Up-regulation Expression CDH1 hsa999
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression SNAI1 hsa6615
Down-regulation Expression VIM hsa7431
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
Result The present results indicated that the combination of TP and TKIs may be a promising therapeutic strategy to treat patients with NSCLCs harboring EGFR mutations.
Combination Pair ID: 550
Ref_18
Pair Name Sulforaphane, Gefitinib
Partner Name Sulforaphane
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Gene Regulation Down-regulation Expression CD44 hsa960
Down-regulation Expression GLI1 hsa2735
Down-regulation Expression GLI2 hsa2736
Down-regulation Expression PROM1 hsa8842
Down-regulation Expression SHH hsa6469
Down-regulation Expression SMO hsa6608
In Vitro Model PC-9 Lung adenocarcinoma Homo sapiens (Human) CVCL_B260
Result The results of the present study demonstrated that SFN inhibits the proliferation of gefitinib-tolerant lung cancer cells via modulation of the SHH signaling pathway. Therefore, combined SFN and gefitinib therapy may be an effective approach for the treatment of lung cancer.
Combination Pair ID: 733
Ref_19
Pair Name Shikonin, Gefitinib
Partner Name Shikonin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->ROS generation
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAD hsa572
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Cleavage CASP3 hsa836
Down-regulation Expression EGFR hsa1956
Down-regulation Phosphorylation MAPK1 hsa5594
Up-regulation Expression PARP1 hsa142
In Vitro Model NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens (Human) CVCL_1483
NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
Result Shikonin-induced cell apoptosis is closely associated with ROS elevation in the cells. These findings indicate that Shikonin can be an effective small molecule treating gefitinib-resistant NSCLC.
Combination Pair ID: 628
Ref_20
Pair Name Sanguinarium, Gefitinib
Partner Name Sanguinarium
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Redox imbalance
Gene Regulation Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Expression BCL-xL hsa598
Up-regulation Expression NOX3 KEGG ID N.A.
In Vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
In Vivo Model The mixture of 1×10⁶ H1975 cells was resuspended in 100 μL of RPMI 1640 medium and 50 μL of Matrigel and injected into the armpit of the right forelimb of 6- to 8-week-old nude mice. Five days later, the mice with tumor formation were administered with sanguinarine via i.p. injection and afatinib via intragastric administration 5 days/week 32 for consecutive days. The tumor growth was monitored every 3–4 days using calipers.
Result Targeting EGFR by elevating ROS and redox imbalance is a potential new strategy to develop a new EGFR inhibitor for TKI-resistant patients with a wide therapeutic window between EGFR(T790M) and EGFR(WT)
Combination Pair ID: 1028
Ref_21
Pair Name Saikosaponin D, Gefitinib
Partner Name Saikosaponin D
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Glycolysis
Gene Regulation Down-regulation Expression ABCC1 hsa4363
Down-regulation Expression ABCG2 hsa9429
Down-regulation Expression ADRB2 hsa154
Down-regulation Expression HK2 hsa3099
Down-regulation Expression HK2 hsa3099
Down-regulation Expression SLC2A1 hsa6513
Down-regulation Expression SLC2A1 hsa6513
In Vitro Model RBE Intrahepatic cholangiocarcinoma Homo sapiens (Human) CVCL_4896
HuCC-T1 Intrahepatic cholangiocarcinoma Homo sapiens (Human) CVCL_0324
Result Saikosaponin D enhances the antitumor effect of gemcitabine by controlling glucose metabolism and drug efflux by inhibiting the ADRB2 signaling. Therefore, the combination of saikosaponin D and gemcitabine may be a potential therapeutic strategy for the treatment of iCCA.
Combination Pair ID: 888
Ref_22
Pair Name Gambogic Acid, Gefitinib
Partner Name Gambogic Acid
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation AKT1 hsa207
Up-regulation Expression BAX hsa581
Down-regulation Expression BCL2 hsa596
Down-regulation Phosphorylation MAPK3 hsa5595
Down-regulation Phosphorylation MEK1 hsa5604
In Vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens (Human) CVCL_1511
In Vivo Model The mice were subcutaneously injected with 1×10⁷ NCI-H1975 cells suspended in 100 uL of Matrigel.
Result Gefitinib in combination with GA resulted in antitumor growth in the EGFR-T790M secondary mutation NCI-H1975 tumor model due to an enhanced apoptotic effect. This novel therapeutic strategy may be a practical approach for the treatment of patients who show gefitinib resistance.
Combination Pair ID: 127
Ref_23
Pair Name Epigallocatechin gallate, Gefitinib
Partner Name Epigallocatechin gallate
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Inhibition-->Autophagy
Gene Regulation Down-regulation Expression ATG5 hsa9474
Down-regulation Expression MAP1LC3B hsa81631
Down-regulation Phosphorylation MAPK1 hsa5594
Up-regulation Expression SQSTM1 hsa8878
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model A549 cells were trypsinized, centrifuged, washed in PBS twice and injected s.c. (1×10⁶, 100 μL of PBS) into the left flanks of the 7–8-week-old mice (the animals were adapted to the lab environment for 7 days before experiments).
Result EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.
Combination Pair ID: 218
Ref_24
Pair Name Cucurbitacin B, Gefitinib
Partner Name Cucurbitacin B
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Apoptosis
Gene Regulation Down-regulation Phosphorylation STAT3 hsa6774
In Vitro Model PC-9 Lung adenocarcinoma Homo sapiens (Human) CVCL_B260
Result CuB reduced the proliferation of GR PC9 cells by modulating the miR‑17‑5p/STAT3 axis, and may represent a promising potential novel strategy for the reversal of GR.
Combination Pair ID: 212
Ref_25
Pair Name Betulin, Gefitinib
Partner Name Betulin
Disease Info [ICD-11: 2C25] Lung cancer Investigative
Biological Phenomena Induction-->Ferroptosis
Gene Regulation Down-regulation Expression GSS hsa2937
Up-regulation Expression ROS1 hsa6098
In Vitro Model A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
NCI-H460 Lung large cell carcinoma Homo sapiens (Human) CVCL_0459
In Vivo Model A xenograft model was constructed in vivo to investigate the role of the combination treatment of betulin and gefitinib in NSCLC tumor growth, it also inhibited the tumor growth of NSCLC in vivo.
Result Co-treatment of betulin and gefitinib is effective against EGFR wild-type/KRAS-mutant non-small cell lung cancer by inducing ferroptosis
03. Reference
No. Title Href
1 Zerumbone combined with gefitinib alleviates lung cancer cell growth through the AKT/STAT3/SLC7A11 axis. Neoplasma. 2023 Feb;70(1):58-70. doi: 10.4149/neo_2022_220418N423. Click
2 Sulforaphane overcomes T790M-mediated gefitinib resistance in vitro through epithelial-mesenchymal transition. J Physiol Pharmacol. 2021 Oct;72(5). doi: 10.26402/jpp.2021.5.09. Click
3 Solamargine enhanced gefitinib antitumor effect via regulating MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway in non-small cell lung cancer. Carcinogenesis. 2023 Aug 18;44(6):497-510. doi: 10.1093/carcin/bgad028. Click
4 6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells. Int J Mol Sci. 2023 Jan 30;24(3):2639. doi: 10.3390/ijms24032639. Click
5 Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway. Life Sci. 2018 Jul 1;204:71-77. doi: 10.1016/j.lfs.2018.05.012. Click
6 The Effects and Mechanisms by which Saikosaponin-D Enhances the Sensitivity of Human Non-small Cell Lung Cancer Cells to Gefitinib. J Cancer. 2019 Oct 22;10(26):6666-6672. doi: 10.7150/jca.30361. Click
7 Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non-small cell lung cancer cells via endoplasmic reticulum stress-mediated degradation of Mcl-1. Mol Carcinog. 2020 Jun;59(6):590-603. doi: 10.1002/mc.23184. Click
8 Luteolin and gefitinib regulation of EGF signaling pathway and cell cycle pathway genes in PC-3 human prostate cancer cells. J Steroid Biochem Mol Biol. 2010 Oct;122(4):219-31. doi: 10.1016/j.jsbmb.2010.06.006. Click
9 Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway. Drug Dev Res. 2023 May;84(3):592-610. doi: 10.1002/ddr.22048. Click
10 AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations. BMC Cancer. 2016 Jul 18;16:491. doi: 10.1186/s12885-016-2519-3. Click
11 Dihydroartemisinin enhances gefitinib cytotoxicity against lung adenocarcinoma cells by inducing ROS-dependent apoptosis and ferroptosis. Kaohsiung J Med Sci. 2023 Jul;39(7):699-709. doi: 10.1002/kjm2.12684. Click
12 Daidzein Synergizes with Gefitinib to Induce ROS/JNK/c-Jun Activation and Inhibit EGFR-STAT/AKT/ERK Pathways to enhance Lung Adenocarcinoma cells chemosensitivity. Int J Biol Sci. 2022 May 16;18(9):3636-3652. doi: 10.7150/ijbs.71870. Click
13 Cryptotanshinone strengthens the effect of gefitinib against non-small cell lung cancer through inhibiting transketolase. Eur J Pharmacol. 2021 Jan 5;890:173647. doi: 10.1016/j.ejphar.2020.173647. Click
14 β-Elemene Synergizes With Gefitinib to Inhibit Stem-Like Phenotypes and Progression of Lung Cancer via Down-Regulating EZH2. Front Pharmacol. 2018 Nov 30;9:1413. doi: 10.3389/fphar.2018.01413. Click
15 Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front Pharmacol. 2019 Mar 22;10:260. doi: 10.3389/fphar.2019.00260. Click
16 Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial-Mesenchymal Transition by Aloe-Emodin Via PI3K/Akt/TWIS1 Signal Blockage. Front Oncol. 2022 May 23;12:908031. doi: 10.3389/fonc.2022.908031. Click
17 Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells. Oncol Rep. 2020 May;43(5):1569-1579. doi: 10.3892/or.2020.7542. Click
18 Sulforaphane reverses gefitinib tolerance in human lung cancer cells via modulation of sonic hedgehog signaling. Oncol Lett. 2018 Jan;15(1):109-114. doi: 10.3892/ol.2017.7293. Click
19 Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol Res. 2017;115:45-55. doi:10.1016/j.phrs.2016.11.011 Click
20 Targeting Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer by Inducing Epidermal Growth Factor Receptor Degradation via Methionine 790 Oxidation. Antioxid Redox Signal. 2016;24(5):263-279. doi:10.1089/ars.2015.6420 Click
21 Saikosaponin D reverses epinephrine- and norepinephrine-induced gemcitabine resistance in intrahepatic cholangiocarcinoma by downregulating ADRB2/glycolysis signaling. Acta Biochim Biophys Sin (Shanghai). 2023 Jul 25;55(9):1404-1414. doi: 10.3724/abbs.2023040. Click
22 Combined therapy with EGFR TKI and gambogic acid for overcoming resistance in EGFR-T790M mutant lung cancer. Oncol Lett. 2015 Oct;10(4):2063-2066. doi: 10.3892/ol.2015.3599. Click
23 EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC. Onco Targets Ther. 2019 Jul 26;12:6033-6043. doi: 10.2147/OTT.S209441. Click
24 Cucurbitacin B enhances apoptosis in gefitinib resistant non‑small cell lung cancer by modulating the miR‑17‑5p/STAT3 axis. Mol Med Rep. 2021 Oct;24(4):710. doi: 10.3892/mmr.2021.12349. Click
25 Co-treatment of betulin and gefitinib is effective against EGFR wild-type/KRAS-mutant non-small cell lung cancer by inducing ferroptosis. Neoplasma. 2022 May;69(3):648-656. doi: 10.4149/neo_2022_211103N1568. Click
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