14 results about "EGFR L858R" patented technology

The present invention relates to the field of gene detection, and particularly to a primer-probe combination, a kit and their applications for detecting the benign and malignant nature of pulmonary nodules. The primer-probe combination includes primer pairs and probes for detecting gene mutation sites and methylation sites, and can achieve simultaneous detection covering the EGFR L858R mutation site, the EGFR 19Del mutation site, and the methylation sites of the HOXA7, CCNA1, and ZNF808 genes at one time. Thus, the present invention is a simple, rapid and accurate combined detection scheme for DNA methylation and gene mutation to assist in differentiating the benign and malignant nature of pulmonary nodules; at the same time, the primer-probe combination can achieve rapid pre-cancer screening, and also has application values such as accurate medication guidance and prognosis and metastasis risk prediction.

The invention belongs to the technical field of gene mutation detection, and particularly relates to an isothermal amplification method and a kit for detecting EGFR-L858R and EGFR-T790M point mutation. One purpose of the invention is to provide a kit for detecting EGFR-L858R and EGFR-T790M point mutation. The kit comprises a capture probe sequence as shown in SEQ ID NO.5 and a signal probe sequence as shown in SEQ ID NO.6, wherein the capture probe sequence is used for detecting L858R point mutation; a capture probe sequence as shown in SEQ ID NO.10 and a signal probe sequence as shown in SEQ ID NO.11, which are used for detecting T790M point mutation. According to the technical scheme, PdAgBP is taken as a solid-phase immobilized substrate, EXPAR isothermal amplification and nucleic acid site LNA padlock are taken as a dual signal amplification mechanism, and biosensors based on BPE-ECL are respectively constructed for detection of point mutation EGFR L858R and EGFR T790M.

The invention relates to the technical field of biological medicines, and provides an EGFR L858R mutation specific long peptide vaccine and application thereof. The long peptide vaccine provided by the invention comprises dendritic cells which are loaded by a long peptide antigen modified by a cell penetrating peptide and are induced to be mature. According to the invention, a long peptide sequence with good immunogenicity and affinity is screened out, and specific T cell immune response can be effectively induced. And the long peptide antigen is modified by adopting cell penetrating peptide (CPPs), so that efficient loading and delivery of the long peptide antigen in dendritic cells (DC) are realized. According to the vaccine, the presentation capacity of antigens is remarkably enhanced, CD8 + T cells can be effectively activated, the expression level of IFN-gamma is remarkably improved, and strong specific immune response is induced. In addition, when the vaccine is used in combination with a PD-1 antibody, the tumor immune microenvironment is further improved, and the immune activation effect is enhanced.

The present invention provides a novel therapeutic means for cancer cells resistant to epidermal growth factor receptor (EGFR)-targeted anticancer agents. Almost no cell death was observed when cancer cells having an exon 19 deletion mutation in the EGFR gene (EGFR Del19), cancer cells having a substitution mutation in which the 790th amino acid threonine in the EGFR protein is substituted with methionine (EGFR T790M), and cancer cells having a substitution mutation in which the 858th amino acid leucine is substituted with arginine (EGFR L858R) were treated solely with aripiprazole or solely with an EGFR-targeted anticancer agent. However, cell viability decreased and cleavage of the apoptosis marker PARP was observed when the cancer cells were treated with aripiprazole in combination with an EGFR-targeted anticancer agent. Therefore, aripiprazole is provided as an enhancer of the anticancer effect of EGFR-targeted anticancer agents.

The present invention relates to a macrocyclic EGFR inhibitor and preparation method therefor and pharmaceutical use thereof. In particular, the present invention relates to an EGFR inhibitor having a structure of formula (I), a pharmaceutical composition thereof, a use thereof as an EGFR inhibitor, and a use thereof in the preparation of a drug for treating and / or preventing tumors or metastatic diseases associated at least partially with EGFR L858R / C797S double mutation, EGFR Del19 / C797S double mutation, L858R / T790M / C797S triple mutation and Del 19 / T790M / C797S triple mutation, especially in the preparation of a drug for treating and / or preventing hyperproliferative diseases and disorders inducing cell death. Each substituent of formula (I) is as defined in the description.

The present invention relates to macrocyclic EGFR inhibitors, methods for their production, and applications in pharmacy. In particular, the present invention relates to EGFR inhibitors having the structure of formula (I), their pharmaceutical compositions, their use as EGFR inhibitors, and their use in the manufacture of drugs for treating and / or preventing tumors or metastatic diseases that are at least partially related to EGFR L858R / C797S double mutations, EGFR Del19 / C797S double mutations, L858R / T790M / C797S triple mutations, and Del19 / T790M / C797S triple mutations, especially their use in the manufacture of drugs for treating and / or preventing hyperproliferative diseases and cell death induction disorder diseases. The definition of each substituent in formula (I) is the same as the definition in the specification. JPEG2025524038000148.jpg6074

The application belongs to the technical field of antitumor drugs, and particularly relates to a 2,4-disubstituted quinazoline compound for inhibiting EGFR, a preparation method and application. As a 2,4-disubstituted quinazoline compound for targeting EGFR L858R / T790M, the compound comprises a compound shown in the following formula or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof has the activity of inhibiting EGFR L858R / T790M, can be used as an inhibitor of EGFR L858R / T790M, has the activity of resisting tumors, and can effectively inhibit the growth of tumor cells.

This invention relates to the field of biodetection technology, providing a logic-gated nanogel probe for live cell typing and its preparation method. The invention uses a thermosensitive polymer nanogel as a carrier, with its surface covalently modified with an antibody that specifically binds to the EGFR L858R mutant protein and a peptide nucleic acid that specifically binds to miR-21. Internally, it encapsulates a self-quenched fluorescent dye. The probe employs an AND logic gating design, triggering gel network dissociation and dye release to generate a fluorescent signal only when it simultaneously recognizes the EGFR L858R protein on the cell surface and captures miR-21 within the cell. This invention solves the problems of high false positive rates in existing single-target detection methods and the inability of traditional liquid biopsy techniques to perform simultaneous genotype-phenotype analysis in situ on live cells. It achieves highly specific and sensitive in situ interpretation of circulating tumor cells, and has significant application value in the field of precision diagnosis and treatment of lung cancer.

The invention relates to an EGFR mutation inhibitor and application thereof. Particularly, the invention relates to an EGFR mutation inhibitor with a structure shown in a formula (I), a pharmaceutical composition of the EGFR mutation inhibitor, application of the EGFR mutation inhibitor as the EGFR mutation inhibitor and application of the EGFR mutation inhibitor in preparation of drugs for treating cancers, tumors or metastatic diseases which are at least partially related to EGFR Del19 mutation, EGFR L858R mutation, EGFR L858R / C797S double mutation, EGFR Del19 / C797S double mutation, L858R / T790M / C797S three mutation and Del19 / T790M / C797S three mutation, the invention particularly relates to application in preparation of drugs for treating hyperproliferative diseases and cell death disorder inducing diseases. Wherein the definition of each substituent in the formula (I) is the same as the definition in the specification.

The invention discloses a nitrogen-containing heterocyclic ring compound as well as a preparation method and application thereof. Specifically disclosed are a compound represented by formula I, and a stereoisomer or a pharmaceutically acceptable salt thereof. The nitrogen-containing heterocyclic ring compound provided by the invention has good proliferation inhibition activity on at least one of EGFR (Epidermal Growth Factor Receptor) Del19-T790M-C797S / BaF3 cells, EGFR L858R-T790M-C797S / BaF3 cells, EGFR Del19-T790M-C797S PC-9 cells and EGFR T790M / C797S / L858R overexpression NCI-H1975 cells. The nitrogen-containing heterocyclic ring compound provided by the invention has the advantages that the proliferation inhibition activity is good;

The invention successfully introduces a new method for targeting a specific EV subgroup based on charged mediated fusion of EV and CLIP. The surface charge of liposomes is modulated by the ratio of positively and negatively charged lipids, an optimal ratio is confirmed that allows for efficient and stable fusion to exosomes. According to the method disclosed by the invention, the advantages of high fusion rate, rapidness and wide applicability of the CLIP are utilized, and the excellent sensitivity and selectivity of the tumor-derived EV miRNA are verified in a cracking-free manner by using microdroplet microfluidic. In particular, the EV-CLIP method enables digitized detection of EGFR L858R and T790M mutations without pretreatment of a sample, and thus enables simplification of the detection process and prevention of EV loss.

The present invention relates to pyrimidine-4,6-diamine derivatives, their preparation methods and pharmaceutical applications. In particular, the present invention relates to a pyrimidine-4,6-diamine derivative having the structure of formula (I), its preparation method, a pharmaceutical composition containing the same, and its use as an EGFR inhibitor and its use in the preparation of a drug for treating and / or preventing at least partially cancer, tumor or metastatic disease associated with EGFR Del19 mutation, EGFR L858R mutation, EGFR L858R / C797S double mutation or EGFR Del19 / C797S double mutation, especially its use in the preparation of a drug for treating and / or preventing hyperproliferative diseases and diseases of impaired induction of cell death. Each substituent of formula (I) is the same as the definition in the specification.

The present invention successfully introduced a new approach to target specific EV subpopulations based on charge-mediated fusion of EVs with CLIP. By adjusting the surface charge of liposomes through the ratio of positively and negatively charged lipids, we identified the optimal ratio for efficient and stable fusion with exosomes. Taking advantage of CLIP's high fusion rate, rapidity, and broad applicability, the present method demonstrated excellent sensitivity and selectivity for tumor-derived EV miRNAs in a lysis-free manner using droplet microfluidics. In particular, the EV-CLIP method enabled digital detection of EGFR L858R and T790M mutations without full sample processing, simplifying the detection process and preventing EV loss.

The present invention successfully introduced a new approach to target specific EV subpopulations on the basis of charge-mediated fusion of EVs and CLIPs. By adjusting the surface charge of liposomes through the ratio of positively and negatively charged lipids, the optimal ratio that allows efficient and stable fusion with exosomes was confirmed. A method according to the present invention uses the advantages of a CLIP's high fusion rate, and rapid and broad applicability, and verified excellent sensitivity and selectivity for disease-derived EV miRNA in a lysis-free manner using droplet-microfluidics. Particularly, the EV-CLIP method enables digital detection of EGFR L858R and T790M mutations without pretreating a sample, and thus can simplify detection processes and prevent EV loss.