42 results about "EGFR T790M" patented technology

The invention relates to a substituted indole or an indole pyrimidine derivative as well as a preparation method, a pharmaceutical composition and application of the substituted indole or the indole pyrimidine derivative, in particular relates to a compound shown in a formula I or pharmaceutically acceptable salt or solvate of the compound, wherein the definitions of R1 to R7, X and Y are claimed as the description and claims. The invention also relates to the preparation method of the compound shown in the formula I, the pharmaceutical composition including the compound, and pharmaceutical application of the compound and the pharmaceutical composition. The compound shown in the formula I provided by the invention is an effective tyrosine kinase irreversible inhibitor, which particularly has a stronger inhibition effect in EGFR-T790M drug-resistant tumors. The formula (1) is shown in the description.

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 provides a substituted diaminopyrimidine compound and medicinal salt thereof. The structure of the substituted diaminopyrimidine compound is as shown in a general formula (I). A pharmacodynamic test proves that the compound is capable of effectively inhibiting growth of multiple tumor cells and can be used for preparing anti-tumor drugs, and meanwhile, the drug resistance of EGFR T790M can be overcome.

The invention discloses a primer probe composition, a kit and a method for detecting EGFR specific gene mutations through 3D (Three-dimensional) digital PCR (Polymerase Chain Reaction). The primer probe composition comprises primers and probes for detecting EGFR gene No.19 to No.21 exon specific mutations, wherein the mutations are EGFR T790M, EGFR L858R, EGFR 2235_2249del15 and EGFR 2236_2250del15. By applying the primer probe composition for detecting the EGFR specific gene mutations through 3D-PCR provided by the invention, four common mutation sites related to lung cancer are included and are respectively detected through the primers and the probes designed according to the different mutation sites, so that the multiple mutations can be detected, the detection efficiency is high, and a result is more intuitive and clearer since the primer probe composition is combined with a 3D-PCR detection method for detecting.

The invention discloses a kit for detecting 22 mutations of EGFR genes by utilizing a digital PCR technology. The kit comprises at least one of a reagent EGFR 19 del, a reagent EGFR T790M and a reagent EGFR L858R, as well as positive quality control and negative quality control. The kit disclosed by the invention is capable of quantitatively determining L858R point mutation, T790M point mutation and 20 deletion mutations of 19 del of the EGFR genes in samples comprising tissue DNA and free DNA of plasma and urine. The primer, probe and kit disclosed by the invention are high in detection accuracy, high in sensitivity and convenient to operate, and reference is made to TKI type drug choice of the targeted EGFR.

The invention discloses a ddPCR detection optimization method of lung cancer EGFR T790M sites and application thereof. The detection optimization method comprises the following steps: optimizing the extraction of cfDNA, and performing PCR amplification and probe detection on the cfDNA by use of the mutant type and wild type fluorescence detection probe designed for the T790M gene sites and a specific primer pair for performing specific amplification on a target region; performing data analysis of a detected fluorescence signal value to acquire the accurate EGFR gene T790M sites information. The noninvasive detection can be really realized by only needing a small amount of peripheral blood. The detection optimization method disclosed by the invention performs detection analysis of the important sites related to the lung cancer target medication in the ctDNA, and provides the medication related gene sites mutant information for the lung cancer patient in the late treatment process of the lung cancer, thereby providing the important reference evidence for the personalized accurate medication guidance, the drug efficacy evaluation and therapeutic monitoring.

The invention belongs to the technical field of medicine and particularly relates to a heterocyclic derivate tyrosine kinase inhibitor shown in the formula (I), a pharmaceutically acceptable salt and ester thereof and stereoisomers thereof, wherein Y, W, Q m, L, R1, R2, R3, R4, R5, R6, R7, R7', R8 and R8' are defined in the specification. The invention further relates to a preparation method of the compounds and a pharmaceutical preparation and pharmaceutical compositions containing the compounds, and application of the compounds as the tyrosine kinase inhibitor for preparing medicine for preventing and / or treating cancer diseases caused by EGFR mutation and drug resistance diseases caused by EGFR T790M mutation.

The invention discloses a detection method of EGFR cis mutation. Based on a Blocker PCR technology, different to-be-detected mutation sites are separately selected on a sense strand and antisense strand of a wild-type EGFR gene to design a corresponding Blocker, and the Blocker can be separately combined with the to-be-detected mutation sites of the sense strand and antisense strand of the wild-type EGFR gene to form a stable hybrid to prevent an upstream primer and a downstream primer from amplifying the wild-type EGFR gene which is subjected to monotonous mutation or trans-mutation. The method is simple and convenient, EGFR cis-configuration mutation can be effectively distinguished from trans-configuration mutation, the sensitivity is high, even 0.1% mutation in a peripheral blood sample can still be detected, and the detection method has a very high application value in clinical diagnosis of drug-resistant mutation of TKI.

The invention relates to the field of gene mutation detection, and discloses a PCR kit for detecting EGFR gene T790M mutation. The PCR kit comprises a nucleic acid amplification reagent and a reference substance, wherein the nucleic acid amplification reagent comprises EGFR T790M reaction solution which comprises a specific primer and a fluorescent probe for detecting the EGFR gene T790M mutation;the reaction solution further comprises a pair of upstream primer and downstream primer and an MGB fluorescent probe; the nucleic acid amplification reagent further comprises 2*QuantStudio 3D DigitalPCR Mix. The invention furthermore discloses a detection method of the PCR kit for detecting EGFR gene T790M mutation. The kit uses digital PCR technology to quantitatively detect T790M mutations intissues or plasma DNA samples of non-small cell lung cancer patients, thereby assisting the formulation of targeted drug treatment protocols for patients.

The invention discloses a method for efficiently detecting EGFR T790M mutant, a probe and a kit for detection. According to the invention, the method for EGFR mutant capture primer hybridization, mononucleotide extension and DNA linkage is adopted for recognizing the EGFR T790M mutant in a sample, converting the EGFR T790M mutant into a capture sequence containing a mutation site and adopting the specific probe and PCR amplification specific to the mutation site for detecting the capture sequence with the mutation site, thereby detecting the existence of the EGFR T790M mutant in the sample. The invention also provides the probe and the kit for detecting according to the method; the detection according to the invention has the characteristics of high sensitivity, high specificity and simple operation; the method is suitable for the clinical examination of the trace EGFR T790M mutant in a blood sample of a tumor patient; new method and thought are supplied for personalized cancer therapy.

The present invention is directed to novel pyrazolopyrimidines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities against BTK and / or EGFR T790M and are useful for the treatment of protein kinases mediated diseases and conditions.

The invention belongs to the field of medicine, and discloses a bis(morpholinyl alkoxyl) quinazoline derivative and a purpose thereof in an anti-tumor aspect. The invention particularly relates to a compound shown by a formula (I), a pharmaceutically acceptable salt of the compound, a preparation method of the compound, a medicine composition containing the compound and the purpose of the compoundin the anti-tumor aspect. The compound has a good inhibition effect on the proliferation of human skin squamous cell carcinoma cell strain A431, human non-small cell lung cancer cell strains A549, human colon cancer cell strains SW480 and human lung cancer cell strains NCI-H1975 containing EGFR T790M / L858R amphimutation. The formula is shown in the description.

The invention relates to the field of tumor cell detection, in particular to a high-sensitive extraction-free kit used for detecting EGFR T790M rare mutation from human peripheral blood CTC. The kit particularly comprises T790M detection reagent, a reference gene detection reagent, a 790 M positive and negative quality control materials and the like. Preferably, a reference gene actin beta gene and a mutant gene are T790M positive quality control materials, and a T790M negative quality control material is process water. An operation method comprises the steps of CTC negative enrichment, PCR amplification, result judgement and the like. The kit has the advantages that according to the technical scheme, a test sample is blood, no genome extraction technology is needed, substrate loss causedby sample extraction is effectively avoided, and the kit is suitable for different stages of cancer patients, and comprises but not limited to early stage, middle stage, late stage, pre-operation andpostoperation therapeutic detection, recurrence detection and the like.

The invention provides a novel kit for detecting EGFR T790M locus gene mutation. A double-phase enzyme system RNase H2 and a DNA polymerase technology are utilized; due to the adoption of a double-enzyme system amplification method, change is made on the basis of a common primer, that is, a spacer arm x is connected to the 3' terminal of a primer sequence SEQ ID NO.1, and therefore a primer can bespecifically combined with a template sequence and can be specifically amplified after RNase H2 is sheared; a primer probe for an EGFR T790M mutation locus is designed, and a fluorescent PCR and closed detection are used, so that the probability of later contamination is reduced; the kit is high in sensitivity, quick in detection and good in stability, and the closed detection reduces the probability of later contamination.

The invention relates to a macrocyclic compound as well as a preparation method and application thereof, the macrocyclic compound has a structure as shown in a formula I, and A, B, D, R1, R2, R3, R4, R5, Z, X, m, n and p are defined in the specification. The macrocyclic compound disclosed by the invention not only can overcome EGFR C797S mutation, but also can overcome EGFR T790M mutation, and is relatively high in selectivity.

The present application provides a compound of formula I, which is a EGFR and ALK dual inhibitor and can be used alone or in combination with other therapeutic agents to treat diseases such as non-small cell lung cancer. The compounds of the present application are useful in the treatment of diseases carrying the EGFR wild-type gene, or carrying the EGFR T790M mutant gene and / or the EGFR L858R mutant gene and / or the EGFR delE746_A750 mutant gene, or in the treatment of diseases carrying the ALK wild-type gene, ALK F1174L mutant gene and / or ALK F1196M gene and / or EML4-ALK mutant gene and / or NPM-ALK mutant gene, and can be used in the first-line treatment of anaplastic lymphoma kinase (ALK) positive late-stage non-small cell Lung cancer.

The invention provides antigen peptide T790M-1 and application to preparation of medicines for treating non-small cell lung cancer thereof. The amino acid sequence of the antigen peptide T790M-1 is shown as SEQ ID NO. 1. The antigen peptide has a function of activating T cells to kill non-small cell lung cancer cells in targeting and provides a novel and promising immunotherapy method for non-small cell lung cancer patients (EGFR-TKIs therapy) in preventing and / or treating EGFR T790M mutations.

The invention discloses a combined preparation and an application of the combined preparation in preparing a non-small-cell lung carcinoma drug. An EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and a preparation for increasing a concentration of glutathione (GSH) in lung carcinoma cells are administered simultaneously or successively. According to the combined preparation and the application, through a systemic research, the GSH plays an important role in resisting the EGFR tyrosine kinase inhibitor to an EGFR T790M mutation non-small-cell lung carcinoma, so that drug resisting cells are sensitive to treatment of the EGFR tyrosine kinase inhibitor again by utilizing a mode of increasing the concentration of the GSH in the lung carcinoma cells; and a cell experiment and an animal experiment prove that the method is safe and effective, can effectively kill the lung carcinoma cells, and can inhibit proliferation of the lung carcinoma cells.

The invention provides an antigen peptide T790M-7 and application thereof in the preparation of a drug for treating non-small cell lung cancer. The amino acid sequence of the antigen peptide T790M-7 is represented by SEQ ID NO.1. The antigen peptide is capable of activating T cells to kill cells of the non-small cell lung cancer in a targeting manner, and a new hopeful immunological therapy method for preventing and / or treating patients with EGFR T790M mutated non-small cell lung cancer (EGFR-TKIs treatment method) can be provided.

Disclosed is a new use of ibrutinib (PCI-32765). In particular, the present invention has found that ibrutinib can treat non-small cell lung cancer carrying EGFR T790M mutations and / or EGFR L858R mutations and / or EGFR delE746_A750 mutations, especially non-small cell lung cancer carrying EGFR L858R and EGFR T790M double mutations.

The present invention provides an EGFR T790M neoantigen epitope peptide and application thereof in tumor treatment. The sequence of the EGFR T790M neoantigen epitope peptide contains one or two different amino acid sequences shown in SEQ ID No.1 and SEQ ID No.2, or an amino acid sequence formed by adding, deleting or substituting one or more amino acids on the basis of one or two different amino acid sequences in SEQ ID No.1 and SEQ ID No.2. The neoantigen epitope peptide can activate T lymphocytes, specifically kill HLA-C*1502 tumor cells with EGFR T790M mutation, and be used for preparing cancer drugs for treating non-small cell lung cancer.

The invention provides antigen peptide T790M-6 and application to preparation of medicines for treating non-small cell lung cancer thereof. The amino acid sequence of the antigen peptide T790M-6 is shown as SEQ ID NO. 1. The antigen peptide has a function of activating T cells to kill non-small cell lung cancer cells in targeting and provides a novel and promising immunotherapy method for non-small cell lung cancer patients (EGFR-TKIs therapy) in preventing and / or treating EGFR T790M mutations.

The present application provides a compound of formula I, which is a EGFR and ALK dual inhibitor and can be used alone or in combination with other therapeutic agents to treat diseases such as non-small cell lung cancer. The compounds of the present application are useful in the treatment of diseases carrying the EGFR wild-type gene, or carrying the EGFR T790M mutant gene and / or the EGFR L858R mutant gene and / or the EGFR delE746_A750 mutant gene, or in the treatment of diseases carrying the ALK wild-type gene, ALK F1174L mutant gene and / or ALK F1196M gene and / or EML4-ALK mutant gene and / or NPM-ALK mutant gene, and can be used in the first-line treatment of anaplastic lymphoma kinase (ALK) positive late-stage non-small cell Lung cancer.

The invention provides antigen peptide T790M-4 and application to preparation of medicines for treating non-small cell lung cancer thereof. The amino acid sequence of the antigen peptide T790M-4 is shown as SEQ ID NO. 1. The antigen peptide has a function of activating T cells to kill non-small cell lung cancer cells in targeting and provides a novel and promising immunotherapy method for non-small cell lung cancer patients (EGFR-TKIs therapy) in preventing and / or treating EGFR T790M mutations.

The invention provides an application of a pharmaceutical composition containing an anti-PD-1 antibody in preparation of drugs for treating advanced non-small cell lung cancer. In addition, the invention also provides a marker, a kit and a method for predicting the therapeutic effect of the pharmaceutical composition. The pharmaceutical composition comprises the anti-PD-1 antibody and a cytotoxic anticancer drug, the drug is used for treating EGFR mutant advanced non-small cell lung cancer patients, and the curative effect of the drug treated by an EGFR small molecule tyrosine kinase inhibitor is failed. The invention provides an effective treatment strategy for a patient who does not have EGFR T790M gene mutation after the EGFR mutant advanced non-small cell lung cancer fails to be treated by an EGFR small molecule tyrosine kinase inhibitor, and genome mutation and expression value efficient treatment are carried out on the patient under the treatment strategy; and the EGFR mutant advanced non-small cell lung cancer patients who can benefit from combined treatment of the anti-PD-1 antibody and the cytotoxic anticancer drugs are accurately selected, and accurate and standardized treatment of the patients is guided.

The invention discloses a class of dialkylaminoquinazoline compounds and their application in the preparation of antitumor drugs. The chemical structure of the compound is R in the formula 1 Represents hydrogen, halogen, ethynyl, propen-1-yl or halogenated benzyloxy; n is an integer of 1 to 3; m is an integer of 1 to 4; R 2 , R 3 Stand alone for C 1 ~C 4 alkyl. The compound of the invention has obvious proliferation inhibitory effect on human colon cancer cells, human non-small cell lung cancer cells, human skin squamous cancer cells and human lung cancer cells containing EGFR T790M / L858R double mutation, and can be used for preparing antitumor drugs.

The invention relates to thiopyrimidine heterocycle anti-tumor compounds as well as a preparation method and an application thereof. The anti-tumor compounds specifically have the structure shown in aformula (I). The invention also relates to the compounds shown in the formula (I), pharmaceutically acceptable salts of the compounds or pharmaceutical composition containing the compounds. The pharmaceutical composition can treat tumor diseases by inhibiting wild type EGFR (epidermal growth factor receptor) and mutant type EGFR-T790M PTK (protein tyrosine kinase) and is particularly applied to treatment of small cell lung cancer, non-small cell lung cancer and EGFR-T790M mutant type non-small cell lung cancer.