36 results about "EGFR L858R" patented technology

The invention discloses quinolinone-containing pyrimido-five-membered heterocyclic compounds and a preparation method and application thereof and belongs to the field of medicinal chemistry. The compounds are shown in the general formula I. The compounds have significant inhibitory and killing effects on a variety of tumor cells such as H1975, A549, PC9, PC3 and HGC and have good inhibitory activity to a human epidermal growth factor receptor EGFR-L858R / T790M mutant in the in-vitro kinase level. The compounds can be used as candidate or lead compounds in preparation of antitumor drugs.

A method for the detection and / or diagnosis of cancer in a patient is disclosed. The method involves detecting circulating tumor cells (CTCs) in a sample obtained from the patient using an antibody specifically binding to an antigen in a protein expressed by the CTCs, wherein the antigen comprises a mutation and wherein the mutation renders the patient receptive or resistance to an anti-cancer drug. Claimed methods include the use of an antibody specific for the EGFR L858R or EGFR exon 19 (ΔE746-A750) mutations for detecting lung cancers and the use of an antibody specific for the K-Ras G12V, K-Ras G12C, K-Ras G12S, K-Ras G12D, or K-Ras G13D mutations for detecting colorectal cancers.

The invention provides a specific T cell receptor (TCR) aiming at EGFR L858R gene mutation and application of specific TCR. The TCR can combine with a new antigen peptide KITDFGRAK-HLA-A*1101 compoundderived from EGFR L858R gene mutation, and the TCR comprises the variable region and constant region of an alpha chain and a beta chain. T cells modified by the TCR has a specific killing effect on the HLA-A*1101 tumor cells of EGFR L858R gene mutation. In addition, the invention provides a pharmaceutical composition for treating tumor expressing the gene mutation, and the pharmaceutical composition is high in specificity and good in individual curative effect.

The invention discloses a method for detecting mutation rate of lung cancer mutation sites. The method comprises the steps that (1) extraction of cfDNA is performed on a plasma sample of peripheral blood of a lung cancer patient to obtain a cfDNA extract; (2) for a lung cancer-associated EGFR L858R site, a first mutant detection probe (the sequence is SEQ ID NO:5) and a first wild type detection probe (the sequence is SEQ ID NO: 6), a first primer (the sequence is SEQ ID NO: 1) and a second primer (the sequence is SEQ ID NO: 2) are designed, and for a lung cancer-associated EGFR 19 exon deletion site, a second mutant detection probe (the sequence is SEQ ID NO: 7) and a second wild type detection probe (the sequence is SEQ ID NO: 8), a third primer (the sequence is SEQ ID NO: 3) and a fourth primer (the sequence is SEQ ID NO: 4) are designed; (3) the cfDNA extract is used as a template for ddPCR detection to obtain an amplification product containing a sensitive mutation site; (4) dataanalysis is performed on the amplification product to obtain the mutation rate of the EGFR sensitive mutation L858R and 19 Del. Thereby, the mutation rates of the EGFR sensitive mutation L858R and 19Del can be obtained sensitively.

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 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 discloses quinolinone-containing pyrimido-five-membered heterocyclic compounds and a preparation method and application thereof and belongs to the field of medicinal chemistry. The compounds are shown in the general formula I. The compounds have significant inhibitory and killing effects on a variety of tumor cells such as H1975, A549, PC9, PC3 and HGC and have good inhibitory activity to a human epidermal growth factor receptor EGFR-L858R / T790M mutant in the in-vitro kinase level. The compounds can be used as candidate or lead compounds in preparation of antitumor drugs.

The invention provides a specific TCR directed at EGFR L858R gene mutation and application of the specific TCR. The TCR has a property of binding to a neoantigen peptide KITDFGRAK-HLA-A*1101 complex derived from the EGFR L858R gene mutation, and the TCR comprises variable regions and constant regions of an alpha chain and a beta chain. A T cell modified by the TCR has a specific killing effect onan HLA-A*1101 tumor cell of EGFR L858R gene mutation. In addition, the invention also provides a pharmaceutical composition for treating tumors related to the expression of the gene mutation. The pharmaceutical composition has the characteristics of strong specificity and good individualized treatment effect.

The invention discloses pyrimidotricyclic compounds or pyrimidotetracyclic compounds having a structure represented by the formula (I), (II) or (III), pharmaceutically-acceptable salts, stereoisomers, or prodrug molecules. The compounds can inhibit various tumor cells, and especially, the compounds can selectively act on lung cancer cells of EGFR L858R / T790 and EGFR E745 A750 / T790M. Compared to wild type cancer cells, the IC50 of the compounds is 10 times, 100 times or even 1000 times higher. The compounds are a novel protein kinase inhibitor, which can overcome the drug resistance of EGFR-TKI and has selectivity.

The present application provides a compound of Formula (I) as an inhibitor against wild-type EGFR and / or mutant EGFR, which may be used for treating human non-small cell lung cancer individually or in combination with other therapeutic agent(s). The compound of Formula (I) of the present application may be used for treating patients of drug-resistant human non-small cell lung cancer harboring wild-type EGFR and / or EGFR T790M mutation and / or EGFR L858R mutation and / or EGFR delE746_A750 mutation.

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 provides a 2-arylamine-4-amido quinazoline compound and a preparation method thereof. The 2-arylamine-4-amido quinazoline compound is shown in a formula I. The compound in the formula I has good inhibitory activity on EGFR L858R / T790M / C797S kinase and can be used for preparing drugs for treating diseases or symptoms related to tumors.

The invention provides a specific T cell receptor (TCR) specific to EGFR L858R gene mutation and application of the TCR. The TCR has the characteristic of combining a new antigen peptide KITDFGRAK-HLA-A*1101 compound derived from the EGFR L858R gene mutation, and comprises variable regions and constant regions of an alpha chain and a beta chain. T cells modified by the TCR has specific killing effect on HLA-A*1101 tumor cells with the EGFR L858R gene mutation. In addition, the invention further provides a drug combination for treating tumors involved in expressing the gene mutation; the characteristics of strong specificity and good individualized treatment effect are realized.

The invention provides a T790M mutant EGFR inhibitor and an application of the same in preparation of antitumor drugs. The inhibitor is a pyrimidine compound with structural characteristics of a formula (I). The compound can inhibit various tumor cells and particularly can act on EGFR L858R / T790M and EGFR E 745_A750 / T790M lung cancer cells selectively, and the IC 50 of the compound is 10 timers and even 100 times higher than that of wild cancer cells. The compound is the protease inhibitor which is capable of overcoming prior EGFR-TKI drug resistance and has selectivity and can be applied to preparation of antitumor drugs. (img file= 'DDAS0000708455660000011. TIF' wi= '716' he= '576' / ).