21 results about "T790M" patented technology

The present invention relates to benzoxazole and benzothiazole compounds or pharmaceutically acceptable salts thereof which are useful for the treatment of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (Exon19 deletion, L858R and the Del 19 / T790M and L858R / T790M resistance mutation). The compounds of the present invention and salts thereof are useful in the treatment or prevention of different types of cancers. The present invention also relates to methods of preparation for benzoxazole and benzothiazole compounds and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof; a pharmaceutical composition containing the compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and / or solvates thereof particularly useful polymorphs of the compounds and salts thereof. The invention also relates to use of the compounds and pharmaceutically acceptable salts, prodrugs, stereoisomers, and solvates thereof in the preparation of a medicament for treating diseases associated with various forms of EGFR. The definitions of 'A', 'X', R1, R2, R3, and 'm' are as defined herein. Formula (I)

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.

This application relates to the field of biological detection technology, and in particular to a primer set, application, kit, and method for detecting EGFR gene T790M and C797S mutations. The primer set includes a forward primer SEQ ID No:1, a reverse primer SEQ ID No:2, and probes SEQ ID No:3 to SEQ ID No:6. The primer set of this application is used to detect EGFR gene T790M and C797S mutations.

The application belongs to the field of molecular biology, and particularly relates to a primer combination for detecting lung cancer EGFR mutant genes based on multiplex PCR-time of flight mass spectrometry and an application and a detection method. The primer combination is at least one EGFR mutant gene site in G719X (2155G>T, 2156G>C, 2155G>A), S768I (2303G>T), 19del (2236_2250del15, 2240_2257del18, 2235_2249del15), L858R (2573T>G), L861Q (2582T>A), T790M (2369C>T), 20ins (2300_2308dup, 2319_2320insCAC, 2310_2311insGGT). The application detects EGFR gene mutations by combining multiplex PCR and time of flight mass spectrometry, and has the advantages of low cost and fast detection speed compared with sequencing, fluorescent PCR and other technical means. The application further relates to an EGFR gene mutation detection kit.

This invention belongs to the field of tumor biology and drug screening technology, specifically disclosing a human EGFR mutation-driven mouse primary lung cancer cell line, its construction method, and its applications. The cell line, ZST-1, is a human EGFR (L858R / T790M) mutation-driven lung cancer cell line derived from mouse primary lung cancer. It is stable, capable of subcutaneous tumor formation in C57BL / 6 mice, and simultaneously expresses Luciferase and tdTomato reporter genes. Its construction method includes obtaining transgenic mice, virus-induced tumor formation, continuous in vivo passage in nude mice, and in vitro culture and screening steps. This cell line can be applied to in vitro screening and efficacy evaluation of human EGFR mutation-targeting drugs, research on EGFR-TKI resistance mechanisms, tumor bioluminescence imaging and fluorescence tracing, and in vivo tumorigenesis and efficacy experiments in an immune-intact C57BL / 6 background.

The present invention relates to benzimidazole compounds or pharmaceutically acceptable salts thereof which are useful for the treatment of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (Exon19 deletion, L858R and the Del 19 / T790M and L858R / T790M resistance mutation). The compounds of the present invention and salts thereof are useful in the treatment or prevention of different types of cancers. The present invention also relates to methods of preparation for benzimidazole compounds and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof; a pharmaceutical composition containing the compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and / or solvates thereof particularly useful polymorphs of the compounds and salts thereof. The present invention also relates to use of the compounds and pharmaceutically acceptable salts, prodrugs, stereoisomers, and solvates thereof in the preparation of a medicament for treating diseases associated with various forms of EGFR. The definitions of X, R1, R2, R3, R4, R5, 'm' and 'n' are as defined herein (Formula I).

Provided are compounds of the Formula I, and salts, hydrates and solvates thereof:wherein R1, R2, R3 and Q1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and / or a C797S mutation) that confer resistance to existing EGFR inhibitors.

Formula (I) The present invention relates to heterocyclic compounds or pharmaceutically acceptable salts thereof which are useful for the treatment of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (Exon 19 deletion, L858R and the Del 19 / T790M and L858R / T790M resistance mutation). The compounds of the present invention and salts thereof are useful in the treatment or prevention of different types of cancers. The present invention also relates to methods of preparation for heterocyclic compounds and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof; a pharmaceutical composition containing the compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and / or solvates thereof particularly useful polymorphs of the compounds and salts thereof. The invention also relates to use of the compounds and pharmaceutically acceptable salts, prodrugs, stereoisomers, and solvates thereof in the preparation of a medicament for treating diseases associated with various forms of EGFR. The definitions of ring A, ring B, R1, R2, R3, R4, 'X' and 'm' and 'n' are as defined herein.

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.

The invention provides a degradation agent targeting EGFRC797S as well as preparation and application thereof, and belongs to the technical field of medicines. The compound as shown in the formula I is prepared, the compound can degrade EGFR in a targeted mode, and expression of EGFR in H1975-M3 cells is remarkably reduced. The compound disclosed by the invention has obvious anti-proliferative activity on a non-small cell lung cancer cell line, particularly has good selectivity on an EGFRL858R / T790M / C797S mutant type H1975-M3 cell and an EGFRL858R / T790M mutant type NCI-H1975 cell, and is obvious in inhibition effect, and the compound disclosed by the invention is low in toxicity on normal cells. Meanwhile, the compound can obviously retard the cell cycle, promote cell apoptosis and inhibit cell invasion and migration. The compound provided by the invention can be used as an EGFRC797S degradation agent to be applied to preparation of non-small cell lung cancer cell resisting drugs. Formula I

This invention discloses EGFR inhibitors, their preparation, and applications. Specifically, this invention relates to a 4-substituted-2-(N-(5-substituted allylamido)phenyl)amino)pyrimidine derivative of formula (I). This series of compounds exhibits activity against L858R EGFR mutants, T790M EGFR mutants, and exon 19 deletion activation mutants, and can be used to treat diseases mediated by EGFR mutant activity, either alone or in part. For example, they have wide applications in the prevention and treatment of cancer, especially non-small cell lung cancer, and hold promise for development into a new generation of EGFR inhibitors.

Provided are compounds of the Formula I, and salts, hydrates and solvates thereof:wherein R1, V1, RN and Q1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and / or a C797S mutation) that confer resistance to existing EGFR inhibitors.

The present disclosure relates to an engineered T-cell Receptors (TCRs) capable of binding to an epitope of an epidermal growth factor receptor (EGFR) comprising a T790M mutation presented on human leukocyte antigen-A (HLA-A)*02:01, wherein the epitope comprises the amino acid sequence of MQLMPFGCLL (SEQ ID NO: 1). Also disclosed are Tcell and BiTE therapies comprising the same, and methods of treating EGFR-TKI resistant lung cancers using the same.

The invention provides a 2, 4-diarylaminopyrimidine derivative containing benzene and heteroaryl as well as a pharmaceutical composition and application thereof, and relates to the field of pharmaceutical chemistry. The invention relates to a 2, 4-diarylaminopyrimidine derivative containing benzene heteroaryl as shown in a general formula I, an optical isomer, a pharmaceutically acceptable salt, a solvate or a prodrug thereof, preparation methods of the derivative and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug thereof and a pharmaceutical composition taking the compound as an active ingredient, and substituent groups R1, R2, R3, R4, A, B and X have meanings given in the specification. The invention further relates to application of the compound shown in the general formula I and the pharmaceutically acceptable salt solvate or the prodrug of the compound in preparation of drugs for treating diseases caused by abnormal high expression of PLK1, EGFRL858R / T790M and EGFRL858R / T790M / C797S kinase, in particular to application in preparation of drugs for treating and / or preventing lung cancer. (I).

Provided herein are compounds of Formula A having an amide-based backbone linked to a plurality of ring structures, pharmaceutically acceptable salts of these compounds, pharmaceutical compositions thereof, and these compounds for use in medical treatment methods as selective allosteric inhibitors of EGFR mutants for the treatment of cancer, the cancer is such as, for example, lung cancer, colon cancer, breast cancer, endometrial cancer, thyroid cancer, glioma, squamous cell cancer, prostate cancer, non-small cell lung cancer (NSCLC) or a cancer with brain metastasis wherein the cancer is characterized by having at least one EGFR mutation selected from the group consisting of L858R, T790M, and C797S.

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;

A compound of formula I or a pharmaceutically acceptable salt thereof, and its use in the preparation of a compound that modulates EGFR tyrosine kinase activity or in the prevention and treatment of EGFR-related diseases. The EGFR inhibitor of formula I exhibits inhibitory activity against EGFR D770-N771 in NPG and NPG / T790M kinases, and inhibits cell proliferation of EGFR-Del19 / T790M / C797S kinase, KC-0122:Ba / F3EGFR-L858R / T790M / C797S triple mutant cell lines, and KC-0116:Ba / F3EGFR-Del19 / T790M / C797S triple mutant cell lines.

The application belongs to the technical field of medicines, and provides a pyrimidine derivative containing a cyclopropane sulfonamide group, a pharmaceutically acceptable salt thereof, a preparation method and application thereof. The pyrimidine derivative containing a cyclopropane sulfonamide group has a structure shown in formula I. The pyrimidine derivative containing a cyclopropane sulfonamide group has a cyclopropane sulfonamide group substituted in the A ring and no alkoxy group substituted in the C ring. The active molecules can not only effectively inhibit the drug resistance of the third generation targeted drug Osimertinib after EGFR C797S mutation, but also can significantly inhibit EGFR single mutation or double mutation (L858R, del 19, T790M). The preparation method of the pyrimidine derivative containing a cyclopropane sulfonamide group and the pharmaceutically acceptable salt thereof has the advantages of simple synthesis process and low cost.

This invention discloses a reagent, kit, method, and application for detecting EGFR gene mutations. The reagent includes a primer set comprising a first primer pair for detecting the EGFR gene mutation site 19del, a second primer pair for detecting the EGFR gene mutation site T790M, and / or a third primer pair for detecting the EGFR gene mutation site L858R. The primer set and probes in this invention for detecting EGFR gene mutations exhibit high sensitivity and specificity, and show no cross-reactivity with wild-type samples, demonstrating promising application prospects.

Provided are a cyclic 2-aminopyrimidine compound having a structure as shown in formula (I), or a pharmaceutically acceptable salt, stereoisomer or prodrug molecule thereof, and a use thereof. The compound can effectively inhibit the activity of EGFR protein kinase drug-resistant mutants (such as EGFRT790M and EGFR19del / T790M / C797S), and can overcome the clinical drug resistance of patients suffering from tumors such as non-small cell lung cancer induced by existing third-generation selective EGFRT790M small molecule inhibitors Osimertinib (AZD9291), Olmutinib (HM6171), Rociletinib (CO-1686) and the like.

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.