58 results about "Egfr tki" patented technology

Methods using mass spectral data analysis and a classification algorithm provide an ability to determine whether a head and neck squamous cell carcinoma (HNSCC) patient is likely to benefit from a drug targeting an epidermal growth factor receptor pathway, including small molecule epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and monoclonal antibody EGFR inhibitors.

The invention discloses a pyrimidine compound, an EGFR inhibitor and application of the EGFR inhibitor. The pyrimidine compound is prepared from a compound shown in the formula I or pharmaceutically acceptable salt thereof, a stereoisomer, and a solvate or prodrug. The EGFR inhibitor contains the pyrimidine compound. The pyrimidine compound can inhibit activated or resistant mutation of one or more kinds of EGFRs, can inhibit proliferation of the EGFR T790M / L858R double-mutant enzyme in the nanomolar concentration, but has a weak inhibiting effect on the wild EGFR enzyme; the pyrimidine compound is applicable to treatment of the EGFR-sensitive mutations cancer and also suitable for cases with secondary dug resistance in present EGFR-TKI treatment; meanwhile, toxic and side effects caused by inhibition on the wild EGFR are greatly reduced due to the mutation selectivity of the pyrimidine compound, and the pyrimidine compound is an ideal treatment drug for diseases caused by EGFR mutation.

The invention discloses a miazines compound, an EGFR inhibitor and application thereof. The miazines compound comprises a compound shown as formula I, or pharmaceutically acceptable salt, stereisomer, solvate or prodrug thereof; and the EGFR inhibitor contains the miazines compound. The miazines compound disclosed by the invention can inhibit the activation or resistant mutation of one or more EGFRs; the multiplication of EGFRT790M / L858R amphimutation enzyme can be inhibited under nanomole concentration, and the inhibition for wild type EGFR enzyme is relatively weak; the miazines compound can be used for the treatment of EGFR sensitive mutation cancers, and is also applicable for cases generating secondary drug resistance in current EGFR-TKI treatment; and moreover, the mutation selectivity greatly reduces toxic and side effects generated by the inhibition of the wild type EGFR, and the miazines compound is an ideal therapeutic drug for diseases caused by EGFR mutation.

The invention discloses probes, primers, a detection system and a kit for detecting mutations of an EGFR gene, and the probes and the primers have the sequences of SEQ ID NO.1 to SEQ ID NO.24. The invention is characterized in that (1), the amplification efficiency is greatly improved to a largest extent; (2) the sensitivity is high, and the detection sensitivity can reach 0.2%; (3) compared with a digital PCR method, operations are simple, the cost is saved, and the clinical application scope is wide; (4) plasma samples with large reaction volume are detected, the DNA sampling quantity of the plasma samples becomes larger, the system is more stable, and the detection rate of the plasma samples is increased; (5) 25 mutations of the EGFR gene can be detected simultaneously in three reaction tubes, and results are intuitive and clear; (6) the detection speed is fast, and consumed time is only 1 / 2 that of the digital PCR; and (7) a detection method can detect peripheral blood samples, has convenient sampling, and can dynamically monitor curative effect of EGFR-TKI drugs on patients.

The invention relates to an application of a biguanide based medicament in medicaments for delaying or reversing acquired drug-resistance of NSELC treated by EGFR-TKI, wherein the biguanide based medicament and EGFR-TKI are taken simultaneously or intervally. The compound is used to delay or reverse generation of EGFR-TKI acquired drug-resistance, and performs varying-degree inhibition effects on main mechanisms of EGFR-TKI acquired drug-resistance of NSCLC patients, and thus the sensibility of the lung-cancer patients to EGFR-TKI is increased, the disadvantage that EGFR-TKI is easy to resist drugs is overcome, and the curative effect of EGFR-TKI is improved.

The invention discloses a medicinal composition for resisting non-small cell lung cancer. The active components of the medicinal composition comprise an artemisinin derivative and EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor), wherein the artemisinin derivative is selected from one of dihydroartemisinin, artesunate, artemether and arteether; and the EGFR-TKI is selected from one of gefitinib, erlotinib, afatinib and osimertinib. The invention also discloses application of the medicinal composition to preparation of medicines for treating and resisting the non-small cell lung cancer. When the medicinal composition provided by the invention is used for treating the non-small cell lung cancer, the medicinal effect which is more excellent than that of the singly used EGFR-TKI can be achieved, the sensitizing effect is achieved, the problem of partial medicine resistance of the non-small cell lung cancer EGFR-TKI is solved, and a scientific basis is provided for the development of new medicines.

The invention relates to quinazolinyl-aryl urea derivatives with antitumor function disclosed as general formula (II) and application thereof. The substituent group in the general formula (II) is defined in the specification. By using sorafenib and gefitinib as lead compounds, the pharmacophore-uramido group of the sorafenib is retained; and meanwhile, the quinazoline rings in the gefitinib and other EGFR-TKIs are retained to synthesize a series of quinazolinyl-aryl urea derivatives. The in-vitro activity test proves that parts of the compounds have excellent antitumor activity, and the compounds have higher research and practical values. (II).

The disclosure provides methods and compositions for treating cancer cells, including cancer cells in a subject, whereby two or more therapeutic agents are used, one being an EGFR-TKI agent and the other being a synthetic oligonucleotide.

The disclosure provides methods and compositions for treating cancer cells, including cancer cells in a subject, whereby two or more therapeutic agents are used, one being an EGFR-TKI agent and the other being a microRNA.

The invention relates to a complex of biguanide and EGFR (Epidermal growth factor receptor)-TKI (Tyrosine kinase inhibitor) or ALK (anaplastic lymphoma kinase)-TKI and application of the complex. The complex can be used for preventing or relieving interstitial pneumonia and particularly the interstitial pneumonia caused by EGFR-TKI or ALK-TKI during treatment of NSCLC (Non-Small Cell Lung Cancer). The complex can prevent complications caused by EGFR-TKI or ALK-TKI during treatment of NSCLC, thereby effectively improving the treatment effect of EGFR-TKI or ALK-TKI and reducing the occurrence and development of complications of a patient.

The invention relates to the field of clinical overcoming of drug resistance of tumors and combined medication, in particular to EGFR-TKIs which can overcome the drug resistance of non-small cell lungcancer by lowering cholesterol. Statins can enhance the antitumor efficacy of EGFR-TKIs. The invention discloses the fact that MbetaCD is used for removing cholesterol from human non-small cell lungcancer cell lines PC-9 / GR and H1975 to enhance the efficacy of gefitinib in resisting the non-small cell lung cancer, enhance the inhibition to signal pathways and enhance the affinity of EGFR and EGFR-TKIs. The statins can synergize with EGFR-TKIs in resisting tumors, inhibit the signal pathways and enhance the affinity of EGFR-TKIs and EGFR without toxic doses, and at the same time, the synergistic anti-tumor efficacy of combined use of the statins and EGFR-TKIs is verified on PC-9 and H1975 nude-mouse transplanted tumor models.

The invention discloses application of a composition of artemisinin or a derivative thereof and an EGFR-TKI targeted drug in preparation of drugs for treating tumors of the head and neck. Experimentsprove that the artemisinin and the derivative (such as dihydroartemisinin) thereof can reverse drug resistance of the tumors of the head and neck to the targeted drug, and when the artemisinin and thederivative thereof are combined to the target drug to treat the tumors of the head and neck, a remarkable synergistic effect is achieved. Through experiments, it proves that the artemisinin and the derivative such as dihydroartemisinin thereof can inhibit protein phosphorylation such as STAT3, paxillin and FAK, by the activity, the effect of resisting the tumors of the head and neck of the targeted drug (such as osimertinib as an EGFR inhibitor) is enhanced, and pharmacological basis is provided for developing new application of artemisinins drugs.

The disclosure provides methods and compositions for treating cancer cells, including cancer cells in a subject, whereby two or more therapeutic agents are used, one being an EGFR-TKI agent and the other being a microRNA.

The invention discloses epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) NXGF and NXGH with antineoplastic activity and a preparing method and application thereof, and belongs to the field of biological medicine. The brand new EGFR TKI are obtained by optimizing and improving the chemical structure of Pelitinib and named NXGF (the formula I) and NXGH (the formula II) respectively. It is shown through research that the synthesized EGFR TKI-NXGF and the synthesized EGFR TKI-NXGH can effectively inhibit proliferation of tumor cells, have a higher proliferation inhibiting effect on the mutation EGFR lung cancer cell line HCC827 compared with Pelitinib, and thus can be clinically applied as an antineoplastic agent. The invention further discloses the preparing method of the EGFR TKI NXGF and NXGH with antineoplastic activity. By proposing the EGFR TKI NXGF and NXGH with antineoplastic activity, and the preparing method and application thereof, an effective technical means is provided for treating tumors and especially non-small cell lung cancer.

The invention discloses epidermal growth factor receptor tyrosin kinase inhibitors IRSF and IRSH with antitumor activity, a preparation method and application thereof. By optimization and improvement of a gefitinib chemical structure, brand-new EGFR TKI (epidermal growth factor receptor tyrosin kinase inhibitors) named as IRSF (shown as formula I) and IRSH (shown as formula II) are obtained. According to researches, the IRSF and IRSH are higher in water solubility and fewer in toxic and side effects and have high inhibition activity on mutant EGFR non-small-cell lung cancer, and the IRSF and IRSH inhibit phosphorylation of cancer cell epidermal growth factor receptor tyrosin kinase to prevent downstream signal path activation so as to promote tumor cell apoptosis. In addition, the invention further discloses a method for preparing the epidermal growth factor receptor tyrosin kinase inhibitors with antitumor activity. The epidermal growth factor receptor tyrosin kinase inhibitors IRSF and IRSH with antitumor activity, the preparation method and application thereof provide effective technical means for tumor treatment, especially treatment of the non-small-cell lung cancer.

The invention discloses a method for adjusting the sensibility of lung adenocarcinoma cells to EGFR-TKIs by mediating progesterone by mPR alpha, according to the method disclosed by the invention, the effects on the sensibility of lung adenocarcinoma cells of different EGFR mutation states to the EGFR-TKIs caused by the mPR alpha are compared, by inducing lung adenocarcinoma sensitive strain PC-9 cells into drug-resistant strain PC-9GR cells, and the relationship of a drug-resistant process and mPR alpha expression is dynamically observed. According to he method for adjusting the sensibility of lung adenocarcinoma cells to the EGFR-TKIs by mediating the progesterone by the mPR alpha, whether the sensibility of lung adenocarcinoma cells of different EGFR mutation states to the EGFR-TKIs can be improved or not after the progesterone is mediated by a membrane receptor is discussed from the point of view of female sex hormone, and a theoretical basis is provided for future research of a lung adenocarcinoma target drug sensitizer.

The invention discloses an EGFR (epidermal growth factor receptor) TKI (tyrosine kinase inhibitor) BF3-AZD9291 with anti-tumor activity as well as a preparation method and application thereof, and belongs to the field of biomedicines. By optimizing and improving the chemical structure of AZD9291, a fully new EGFR TKI is obtained, and is named as BF3-AZD9291 (formula I). Proofed by study, the synthesized EGFR TKI BF3-AZD9291 has the advantages that the drug resistance of tumor cells can be effectively inhibited; compared with AZD9291, the stronger drug resistance inhibiting function is realizedfor the mutation EGFR tumor cell line H1975T790M, and the EGFR TKI BF3-AZD9291 can be used as an anti-tumor reagent in clinical application. The invention also discloses the method for preparing theEGFR TKI BF3-AZD9291 with the anti-tumor activity. The EGFR TKI BF3-AZD9291 provides an effective technical method for the treatment of tumors, especially non-small cell lung cancer. (The formula I isshown in the attached figure.).

The present invention provides methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4 / 6 inhibitor described herein in combination or alternation with an EGFR-TKI to delay or reverse acquired resistance to previously administered EGFR-TKIs. In addition, methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4 / 6 inhibitor described herein in combination or alternation with an EGFR-TKI are provided wherein an intrinsically EGFR-TKI resistant EGFR-mutant cancer is sensitized to the effects of the EGFR-TKI.

The invention discloses an EGFR (epidermal growth factor receptor) kinase inhibitor and application thereof in preparation of anti-cancer drugs, the EGFR kinase inhibitor can effectively improve EGFRTKI acquired drug resistance caused by SQSTM1 accumulation by weakening EGFR TKI alkalinity, and the EGFR kinase inhibitor is of great significance to increase of clinical treatment income of EGFR TKI.

The invention belongs to the field of antitumor drugs and specifically discloses application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer). In comparison with the fact that osimertinib is applied alone to treat EGFR(+) NSCLC, the drug combination of the aspirin and the osimertinib can effectively inhibit proliferation of the EGFR(+) NSCLC cells, so as to promoteapoptosis of the EGFR(+) NSCLC cells. The drug combination of the aspirin and the osimertinib enhances sensitivity of the NSCLC patient to EGFR-TKI, overcomes the defect of highly possible drug resistance to the osimertinib, increases the effective treatment time of the osimertinib and can further improve the prognosis of the EGFR(+) NSCLC patient.

Provided is a therapeutic agent and a therapeutic method for EGFR-TKI-resistant non-small cell lung cancer. Provided are: a therapeutic agent that contains an anti-HER3 antibody-drug conjugate as an active ingredient; or a therapeutic method characterized by administering an anti-HER3 antibody-drug conjugate.

The present invention relates to pharmaceutical formulations of highly active drugs with limited shelf-life in aqueous media, suitable to be administered by a caregiver person to a patient avoiding or minimizing the risk of exposure, contact or contamination of the caregiver person with the active product ingredient (API), preferably an EGFR-TKI such as afatinib dimaleate.

The invention relates to the field of tumor drug treatment, in particular to application of an autophagy inhibitor for overcoming drug resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in treatment of non-small cell lung cancer. The autophagy inhibitor is chloroquine. The EGFR-TKI is erlotinib. The method and application has the beneficial effects that autophagy is involved in development of the EGFR-TKI drug resistance of non-small cell lung cancer, the autophagy inhibitor chloroquine can overcome the drug resistance of the EGFR-TKI by inhibiting autophagy, and combination of the chloroquine and the erlotinib can effectively kill lung cancer cells resistant to the erlotinib inside and outside bodies.

The invention discloses a method for detecting sensitive mutation of an EGFR-TKI (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor) based on extracellular vesicle DNA (Deoxyribonucleic Acid). The method comprises the following specific steps: (1) extracting extracellular vesicles EVs in body fluid of a tumor patient through a conventional extracellular vesicles EVs extraction method, soas to obtain the extracellular vesicles EVs; (2) damaging structures of the extracellular vesicles EVs under the action of a surfactant and releasing DNA; obtaining target DNA through a conventional DNA extraction method; (3) detecting through a common EGFR-TKI sensitive mutation method. The method disclosed by the invention is used for detecting EGFR mutation and has an accurate result and high sensitivity and specificity.

The invention belongs to the technical field of biology medicine, and relates to an anti-pancreas cancer pharmaceutical composition, an application, a pill case and a package. The pharmaceutical composition, the pill case and the package contain amiloride with therapeutically effective amount and an epidermal growth factor tyrosine kinase inhibitor EGFR-TKI with therapeutically effective amount which are can be taken as a combined preparation and used in a simultaneous, separating or orderly mode, wherein the mol ratio of amiloride to erlotinib is 500: 1-1: 50. When the pharmaceutical composition, the pill case and the package are used for treating tumor, the drug efficiency which is better than that of erlotinib with individual usage can be obtained, and the clinic chemotherapy effect is increased.

The disclosure provides methods and compositions for treating cancer cells, including cancer cells in a subject, whereby two or more therapeutic agents are used, one being an EGFR-TKI agent and the other being a synthetic oligonucleotide.

The invention relates to methods for preventing or treating resistance to EGFR inhibitors in cancer patients. More particularly, after performing a screen for small molecules potentially capable of countering cancer resistance to EGFR TKI, inventors identified the multikinase inhibitor sorafenib, which has the property, in combination with EGFR TKI, to prevent the enrichment of tumor cells containing mutations responsible for NSCLC resistance to first and third generation EGFR TKI. These data indicate that this multikinase inhibitor can prevent resistance to several generations of EGFR TKI. These in vitro data were confirmed in an in vivo xenograft mouse model of NSCLC. Finally these data were reproduced in cancer cells using SC-1, a sorafenib analogue. Accordingly, the invention relates to a method of preventing and / or treating cancer resistance to treatment with an epidermal growth factor receptor (EGFR) inhibitor in a subject in need thereof comprising administering to the subject sorafenib drug or sorafenib analogue, alone or in combination with an EGFR inhibitor.

The invention discloses an application of an EZH2 inhibitor in preparation of drugs for treatment of non-small cell lung cancer. The EZH2 inhibitor is GSK343 and DZNep, the inhibitor GSK343 or DZNep can be compounded with the first-generation EGFR-TKI drugs, respectively, the drug resistance of non-small cell lung cancer can be effectively reduced, the migration and proliferation of cancer cells are inhibited, and application provides a novel treatment idea for the treatment of lung cancer, which has brought good news to the patients.

The invention discloses application of acetyltanshinone IIA in preparation of a medicine for treating lung cancer and the medicine for treating lung cancer, and belongs to the technical field of medicines. According to the scheme, the application of the acetyltanshinone IIA in treating lung cancer, especially non-small cell lung cancer (NSCLC) is provided, and the small molecule compound acetyltanshinone IIA can be used for resisting primary and acquired drug resistance of NSCLC cells to epidermal growth factor receptors, namely tyrosine kinase inhibitors (EGFR TKIs). The invention further determines the molecular target of the ATA, and clarifies the mechanism of the ATA for inhibiting the growth of drug-resistant NSCLC cells and tumors. The drug containing the acetyltanshinone IIA is expected to be developed into a multi-target anticancer agent for treating TKI drug-resistant NSCLC.

The invention provides a method for predicting the response of an EGFR-activating mutant subject suffering from a lung adenocarcinoma and receiving treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a method for predicting prognosis in an EGFR-activating mutant subject suffering from a lung adenocarcinoma and receiving treatment with EGFR-TKI. In the methods of the invention, clustered genomic alterations in specific chromosomes (in particular chromosomes 5p, 7p, 8q or 14q) are determined as a tool for predicting the response or prognosis.