BIOMAT Database Logo BIOMAT Database Logo

Discovery of 4,6-pyrimidinediamine derivatives as novel dual EGFR/FGFR inhibitors aimed EGFR/FGFR1-positive NSCLC. 2020

Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

FGF2-FGFR1 autocrine pathway activation reduces the sensitivity of non-small cell lung cancer (NSCLC) cells to EGFR inhibitors like Gefitinib. Therefore, dual-specific drugs targeting EGFR and FGFR with high selectivity and activity are required. Through structure analysis of excellent EGFR inhibitors and FGFR inhibitors, we designed and synthesized 33 4,6-pyrimidinediamine derivatives as dual EGFR and FGFR inhibitors and selected BZF 2 as a potential EGFR and FGFR inhibitor after initial cell screening. Then, through kinase testing and western blot analysis, BZF 2 was defined as a dual EGFR and FGFR inhibitor with high selectivity 1and activity. Biological evaluation of NSCLC cell lines with the FGF2-FGFR1 autocrine loop indicated that BZF 2 significantly inhibited cell proliferation (IC50 values for H226 and HCC827 GR were 2.11 μM, and 0.93 μM, respectively), cell migration, and induced cell apoptosis and cell cycle arrest. Anti-tumor activity test in vivo showed that BZF 2 obviously shrank tumor size. Therefore, BZF 2 is a highly selective and potent dual EGFR/FGFR compound with promising therapeutic effects against EGFR/FGFR1-positive NSCLC.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D003959 Diamines Organic chemicals which have two amino groups in an aliphatic chain. Diamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of 4,6-Disubstituted Pyrimidine Derivatives as Novel Dual VEGFR2/FGFR1 Inhibitors.
May 2021, Chemistry & biodiversity,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of a prominent dual-target DDR1/EGFR inhibitor aimed DDR1/EGFR-positive NSCLC.
May 2024, Bioorganic chemistry,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC.
November 2021, European journal of medicinal chemistry,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of Benzo[g]quinazolin benzenesulfonamide derivatives as dual EGFR/HER2 inhibitors.
December 2017, European journal of medicinal chemistry,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery and optimization of tetrahydropyrido[4,3-d]pyrimidine derivatives as novel ATX and EGFR dual inhibitors.
May 2018, Bioorganic & medicinal chemistry,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of a series of novel phenylpiperazine derivatives as EGFR TK inhibitors.
September 2015, Scientific reports,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth.
October 2020, Signal transduction and targeted therapy,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Combined FGFR and Akt pathway inhibition abrogates growth of FGFR1 overexpressing EGFR-TKI-resistant NSCLC cells.
July 2021, NPJ precision oncology,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Discovery and evaluation of cytisine N-isoflavones as novel EGFR/HER2 dual inhibitors.
October 2022, Bioorganic chemistry,
Zixin Xie, and Kaiqi Wu, and Yuexuan Wang, and Yaqian Pan, and Bo Chen, and Donghua Cheng, and Suwei Pan, and Taoning Guo, and Xuze Du, and Longcheng Fang, and Xuebao Wang, and Faqing Ye
Rational design-aided discovery of novel 1,2,4-oxadiazole derivatives as potential EGFR inhibitors.
September 2021, Bioorganic chemistry,
Copied contents to your clipboard!