84 results about "Osimertinib" patented technology

The invention provides application of a copper death inducer in preparation of a medicine for treating osimertinib-resistant non-small cell lung cancer, and belongs to the technical field of treatment of non-small cell lung cancer. According to the invention, through high-throughput drug screening, the copper death inducer copper diethyl dithiocarbamate (CuET) and osimertinib are combined for use, so that a remarkable synergistic anti-cancer effect is achieved; furthermore, through detection of a wild type and osimertinib drug-resistant cell line model, an osimertinib sensitive and drug-resistant patient-derived organoid and a mouse xenotransplantation model, it is found that the anti-tumor effect of osimertinib can be remarkably enhanced through copper death induction, and osimertinib drug resistance is overcome. According to the technical scheme provided by the invention, osimertinib drug-resistant non-small cell lung cancer cells can be effectively killed, the curative effect of osimertinib in sensitive and drug-resistant models is remarkably enhanced, and an application scene is provided for copper death in tumor treatment.

The invention discloses a method for constructing an osimertinib curative effect prediction model based on an elastic score and T790M mutation, and relates to the technical field of biological medicines, and the method is technically characterized in that the osimertinib curative effect prediction model based on the elastic score and the T790M mutation is constructed; the interaction mechanism between the radiomics characteristics and the EGFR mutation state is explored, so that a more accurate decision basis is provided for personalized clinical treatment, and the treatment effect is improved.

The invention provides a pharmaceutical composition for treating non-small cell lung cancer and application of the pharmaceutical composition. The pharmaceutical composition comprises gefitinib, erlotinib, afatinib, neratinib, osimertinib and the like which serve as active ingredients. The pharmaceutical composition disclosed by the invention can simultaneously contain various EGFR inhibitors as active ingredients, and the active ingredients are controlled at ultra-low dosage, so that the pharmaceutical composition not only can ensure the treatment effect, even the drug effect of the pharmaceutical composition is obviously superior to that of a high-dosage EGFR inhibitor independent administration group, but also can ensure the safety, and the pharmaceutical composition is suitable for clinical application. And after the active components are combined, a good synergistic effect is achieved, and more importantly, the occurrence of drug resistance can be remarkably reduced or even resisted. In a lung cancer cell culture experiment, the EGFR inhibitor independent administration group has a drug resistance phenomenon at the earliest 20 days, but the pharmaceutical composition group still has no drug resistance phenomenon after 160 days of administration.

The invention belongs to the field of gene engineering, and particularly designs oligonucleotide and application thereof in preparation of a medicine for treating osimertinib drug-resistant non-small cell lung cancer. Research finds that 3 'tRF-mtAsnGTT is highly expressed in osimertinib drug-resistant non-small cell lung cancer cells, and the inventor designs an effective oligonucleotide capable of specifically inhibiting the function of 3' tRF-mtAsnGTT, so that tumor cell proliferation is inhibited, cell apoptosis is promoted, and the drug sensitivity of the cells to osimertinib is remarkably improved. The invention provides a novel targeting strategy and application approach for molecular intervention and combined treatment of osimertinib resistance of non-small cell lung cancer.

The application discloses a combined drug for treating lung cancer. It is found for the first time that lomethixol can be used alone or in combination with other drugs to have a significant anticancer effect on NSCLC patients and NSCLC patients resistant to osimertinib, and in addition, it is found that lomethixol is a potential autophagy inducer and can activate cell autophagy. The application provides a new clinical treatment method for NSCLC patients and NSCLC patients resistant to osimertinib, and has a wide application prospect.

Described herein are methods and compositions related to methylation-based determination and characterization of subjects afflicted with various stages of cancer, including lung cancer and non-small cell lung cancer (NSCLC). Osimertinib is one of the most common precision therapies in non-small cell lung cancer but nearly all patients eventually progress due to somatic mutations and cellular plasticity that bypass the treatment. Defining the cellular plasticity state with epigenetics will help physicians know when to switch therapies.

The present application relates to a kind of anti-non-small cell lung cancer for strengthening healthy qi and resolving stasis and preparation method thereof, strengthening healthy qi and resolving stasis is made from the following weight proportion of raw medicinal materials: Ficus pumila 2g~50g / portion, radix pseudostellariae 2g~50g / portion, poria cocos 2g~50g / portion, atractylodes 2g~50g / portion, radix scutellariae 2g~50g / portion, oldenlandia 2g~50g / portion, cat's paw grass 2g~50g / portion, giant knotweed 2g~50g / portion, curcuma zedoary 2g~50g / portion, oyster 2g~50g / portion, platycodon 2g~50g / portion, mountain bitterling 2g~50g / portion, half branch orchid 2g~50g / portion. By cell test and the construction NSCLC osimertin drug resistance animal model prove, strengthening healthy qi and resolving stasis of the present application can adjust tumor microenvironment (TME) and inhibit non-small cell lung cancer cell growth of osimertin drug resistance. Not only this, strengthening healthy qi and resolving stasis of the present application can also inhibit common non-small cell lung cancer cell growth. While clinical observation finds, strengthening healthy qi and resolving stasis of the present application can improve insomnia, skin rash, diarrhea and other symptoms of lung accumulation (lung cancer, lung nodule) patient, improve its quality of life.

This specification describes an improved process for the manufacture of osimertinib.

Disclosed herein are methods of determining whether a subject suffering from non-small cell lung cancer (NSCLC) is sensitive to treatment with osimertinib. In some embodiments, the method comprises obtaining an experimental matrix comprising a mutation status of at least one gene in an experimental sample associated with the subject, applying the obtained experimental matrix to a model, the model being based on a partitioning matrix comprising, for a plurality of reference samples, a mutation status of at least one gene and a sensitivity label for each of the plurality of reference samples indicating whether a corresponding reference subject is sensitive to osimertinib, wherein the at least one gene of the partitioning matrix corresponds to the at least one gene of the experimental matrix, and determining the subject as sensitive to treatment with osimertinib based on a result of the applied model.

The invention discloses a 2-amino-4-anilino pyrimidine compound as well as a preparation method and application of the 2-amino-4-anilino pyrimidine compound. The compound has a strong inhibition effect on EGFR (epidermal growth factor receptor) gene mutation targets and c-MET and has a strong inhibition effect on osimertinib drug-resistant cells; and the compound can inhibit proliferation of various tumor cells, and provides excellent application prospects for treatment of EGFR gene mutation and MET amplified malignant tumors.

Targeted therapy using osimertinib (an EGFR tyrosine kinase inhibitor), is the first choice for patients with metastatic or recurring lung cancer. However, most patients develop resistance. Because the options after failure of TKls such as osimertinib are limited, improving EGFR-targeted therapy is an unmet need. Here, EGFR mutant patient-derived xenograft tumors responded partially to osimertinib despite near complete inhibition of EGFR activation. Many tumor cells escaped drug killing and regained growth following about 35 days of continuous osimertinib dosing. However, when an antibody to hepatoma-derived growth factor was given concurrently with osimertinib, tumors showed complete or near complete responses with significant prolongation of progressionfree survival of tumor bearing mice. The data support the idea that increased suppression of the AKT / mTOR and MAPK pathways is a mechanism that enhances efficacy of osimertinib when it is combined with an anti-HDGF antibody.

Provided herein are combination therapies comprising a SHP2 inhibitor (e.g., Compound 1) and an EGFR inhibitor (e.g., osimertinib or cetuximab) and methods of using such combination therapies.

The invention relates to application of combination of Arovestone and osimertinib in preparation of a medicine for treating non-small cell lung cancer. According to the application disclosed by the invention, the fact that the acrovestone can inhibit the proliferation of PC9-OR cells is found for the first time, in-vivo experiments prove that the acrovestone can inhibit the growth of lung in-situ tumors of the PC9-OR cells, and a new treatment strategy is provided for treating osimertinib drug-resistant non-small cell lung cancer.

The invention discloses application of irbesin in overcoming drug resistance of tumor cells. The invention proposes and verifies that the irbesin can significantly reduce the activity of osimertinib drug-resistant tumor cells by inducing cancer cell ferroptosis for the first time, further enhances the treatment effect of osimertinib, inhibits the progress of drug-resistant non-small cell lung cancer, and provides a new direction for treatment of osimertinib drug-resistant lung cancer.

The invention belongs to the field of biological medicines, and particularly relates to application of a compound to preparation of a medicine for treating papilloma of the upper respiratory tract. The invention provides an application of a compound in preparation of a medicine for treating and / or preventing papilloma of the upper respiratory tract, and is characterized in that the compound comprises one or more of asperisib, crizotinib, lapatinib, osimertinib and bortezomib. Experimental results show that the asperisib, crizotinib, lapatinib, osimertinib and bortezomib can realize long-term control on the papilloma of the upper respiratory tract and reduce the recurrence risk of the papilloma of the upper respiratory tract to a certain extent, so that the life quality of patients with the papilloma of the upper respiratory tract can be improved; the invention has important scientific value and clinical application prospect in the field of upper respiratory papilloma treatment.

The application relates to application of 6-(2-hydroxyethyl)benzo[d]thiazole-4-ol combined with osimertinib in preparation of a drug for treating non-small cell lung cancer. A drug for preventing and / or treating human non-small cell lung cancer is provided, and active ingredients of the drug include 6-(2-hydroxyethyl)benzo[d]thiazole-4-ol (HBT) and osimertinib. The application provides that HBT is used for reversing drug resistance of osimertinib in treatment of non-small cell lung cancer, and can be combined with osimertinib, so that a good treatment effect of non-small cell lung cancer is obtained.

The invention discloses an SNP (Single Nucleotide Polymorphism) site combination for detecting osimertinib induced SJS / TEN and application of the SNP site combination. The SNP site combination can be used for effectively predicting the risk of osimertinib induced SJS / TEN. According to the invention, SNP site detection is used for replacing the prior art in which complex HLA whole genotyping is adopted to predict osimertinib-induced SJS / TEN, and the method has the advantages of time advantage, cost economy, simplicity and convenience in operation, easiness in data analysis and the like, and is expected to become an important member in conventional detection items in various scales of medical institutions throughout the country.

This invention belongs to the field of drug synthesis technology, specifically relating to a method for synthesizing an intermediate of osimertinib. The invention uses 1-methyl-3-acetylindole as a starting material and reacts it with ethyl formate to obtain an intermediate. This intermediate, without purification, is directly cyclized with 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)guanidine to prepare N... 1 -(2-(dimethylamino)ethyl)-5-methoxy-N 1 -methyl-N 4 -(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine. This synthetic route has mild reaction conditions, simple post-processing, and high yield, making it suitable for industrial production.

The invention relates to an application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer, and particularly relates to the following aspects: (1) osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and shows a remarkable curative effect in treatment of non-small cell lung cancer (NSCLC) patients carrying specific EGFR mutation; (2) chidamide is a novel oral HDACi, can induce cell apoptosis, cell cycle arrest and cell growth inhibition, and shows good tolerance and antitumor activity in various cancer types; and (3) chidamide is taken as an epigenetic regulating agent and can be in synergistic effect with osimertinib, so that the capability of killing lung cancer cells is enhanced. The invention belongs to the technical field of medicines, and particularly provides application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer.

The invention relates to the field of biological medicine, and provides an HDAC inhibitor coated liposome degradation agent, which comprises hydrogenated lecithin, cholesterol, an HDAC inhibitor, targeted EGFR drug modified functional phospholipid and E3 ligase ligand modified functional phospholipid. The invention further provides a preparation method of the liposome degradation agent wrapping the HDAC inhibitor and application of the liposome degradation agent in preparation of antitumor drugs. The EGFR-targeted liposome degradation agent is combined with the HDAC inhibitor, malignant proliferation of the osimertinib-resistant non-small cell lung cancer is synergistically overcome from multiple channels, and a new treatment thought is expected to be provided for clinical osimertinib-resistant lung cancer patients.

The invention discloses a composition as well as a preparation and application thereof. The composition is prepared from solamargine and osimertinib according to a molar ratio of 1: (0.25 to 4). Wherein the dosage of the solamargine is 0.5 to 32 [mu] M. According to the invention, solamargine and osimertinib are combined to treat lung cancer for the first time, and it is accidentally found that solamargine and osimertinib have an obvious synergistic anti-cancer effect under multiple proportions and doses; moreover, the coordination effect is more fully embodied on drug-resistant lung cancer cells, and a new way is brought to clinical treatment of drug-resistant lung cancer.

Bispecific antibody against EGFR and c-Met. The heterodimeric interaction between the EGFR binding arm and the c-Met binding arm of the bispecific antibody is stronger than the interaction of each in the source homodimer by modifying the Fc segment amino acid sequence of the binding arm, so that it can be assembled into a heterodimer in vitro; its effect on inhibiting the proliferation of EGFR and c-Met double-positive tumor cells is stronger than the combination of EGFR monoclonal antibody and c-Met monoclonal antibody, mediates antibody-dependent cellular cytotoxicity (ADCC), promotes target protein internalization and inhibits the proliferation of osimertinib acquired resistant cell lines. Since the prepared bispecific antibody is simple to prepare, stable in structure, and can obtain a pure bispecific antibody by in vitro assembly, it is expected to better meet the clinical treatment needs, and therefore has a good market prospect.

The invention provides a targeted ER beta protein degradation agent as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the present invention, based on a selective ER beta efficient agonist ERB-041, an ER beta-targeted protein degradation agent ERB-2 is synthesized; eRbeta is used as an NSCLC related transcription factor and is positively correlated with the expression level of antioxidant enzyme SOD2, so that oxidative stress induced by osimertinib is inhibited, and osimertinib drug resistance is promoted. According to the ERB-2 prepared by the invention, the expression level of SOD2 is down-regulated through targeted degradation of ER beta, so that a cell antioxidant system is inhibited, oxidative stress and cell death induced by osimertinib are enhanced, and the osimertinib drug resistance in NSCLC is overcome.

The application belongs to the field of medicine and biotechnology, and particularly relates to an artificially circularized circular RNA and application thereof. The application provides an artificially circularized circular RNA, wherein the nucleotide sequence of the circular RNA is shown as SEQ ID NO. 1. The circular RNA (circmiR) can inhibit the function of miRNAs, improve the endogenous PTEN mRNA and PTEN protein levels, and enhance the sensitivity of LUAD to osimertinib. The results of examples show that the circmiR can improve the endogenous PTEN mRNA and PTEN protein levels, down-regulate the PI3K / AKT signaling pathway, and then significantly inhibit the proliferation, migration and invasion of LUAD cell lines, and can significantly enhance the sensitivity of the LUAD osimertinib-resistant cell line to osimertinib. The circular RNA based on the application can provide a new treatment mode for LUAD, and provide a new treatment strategy for LUAD osimertinib-resistant patients.

The invention discloses a solamargine and osimertinib co-loaded liposome nano preparation as well as preparation and application thereof. The nano preparation is prepared from solamargine and osimertinib according to a molar ratio of 1: (0.25 to 4.34). Wherein the dosage of the solamargine is 0.5 to 32 [mu] M. According to the invention, solamargine and osimertinib are combined to treat lung cancer for the first time, and it is found that the solamargine and osimertinib have an obvious synergistic anti-cancer effect under multi-proportion and multi-dose conditions; moreover, the coordination effect is more fully embodied on drug-resistant lung cancer cells, and a new way is brought to clinical treatment of drug-resistant lung cancer. According to the invention, the solamargine and osimertinib co-loaded liposome nano preparation is prepared for the first time, and the nano preparation has remarkable tumor targeting property, can be better gathered at tumor tissue parts, exerts an anti-tumor growth effect, and reduces toxic and side effects generated by free drugs to a certain extent; meanwhile, the nano preparation can be used for remarkably reversing the osimertinib drug resistance effect of lung cancer.

The invention particularly discloses application of an EP2 inhibitor in preparation of a medicine for preventing and / or treating lung cancer in combination with osimertinib, and relates to the technical field of tumor treatment. The invention provides an application of an EP2 inhibitor in preparation of a medicine for preventing and / or treating lung cancer in combination with osimertinib, and by inhibiting an EP2 receptor, the anti-tumor effect of osimertinib is enhanced and the occurrence of drug resistance is delayed.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in EGFR-mutant lung cancer patients, including those with brain metastases. However, osimertinib-treated patients often develop lethal metastatic relapse, often to the brain. The genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients, and is identified as a novel, therapeutically targetable S100A9-ALDH1A1-RA axis. A combination of osimertinib and AGN-194310, for example, treats such cancer while avoiding metastatic relapse.

The invention provides a preparation method of osimertinib, which belongs to the field of chemical synthesis and comprises the following steps: performing palladium-carbon catalytic hydrogenation reduction on a compound I serving as a raw material; after reduction is finished, hydrogen protection is replaced by nitrogen protection, then 3-chloropropionyl chloride and organic alkali are added, after acylation reaction is finished, direct heating is performed to generate elimination reaction, and a compound II osimertinib is obtained through refining. According to the process, reduction acylation elimination is carried out in the same reaction system, meanwhile, 3-chloropropionyl chloride which is cheaper and easier to obtain is used, acryloyl is eliminated and introduced after acylation, and the whole synthesis process is efficient, economical and environmentally friendly. According to the method, a one-pot strategy is utilized for the first time to combine multiple steps of reactions into one step, the reductive acylation elimination reaction of the compound I is simply and efficiently achieved, and synthesis of osimertinib is completed.

UQCC2-based computer-assisted method, system, and device for diagnosing osimertinib-resistant lung cancer, predicting drug treatment effects, and screening drugs targeted for osimertinib-resistant lung cancer are provided. The method includes receiving input data, the input data including expression level data of UQCC2 in a patient with lung cancer; generating, based on the input data, an indication of whether the patient with lung cancer is a patient with osimertinib-resistant lung cancer through a machine learning model, a lung cancer including non-small cell lung cancer. The disclosure first discovers the significant overexpression of UQCC2 in the osimertinib-resistant lung cancer and the functional interaction between UQCC2 and METTL3, and provides an efficient and rapid method for diagnosing the patient with osimertinib-resistant lung cancer, predicting the drug treatment effect on the patient with osimertinib-resistant lung cancer, and screening drugs based on targeting UQCC2 and METTL3, demonstrating critical research significance for related disease prevention and treatment.

This invention belongs to the field of medical and pharmaceutical technology, and specifically relates to an antibacterial composition and its application. It comprises osimertinib mesylate and polymyxin. This invention is the first to demonstrate the novel pharmaceutical use of osimertinib mesylate as a synergistic antibacterial adjuvant for polymyxin. Experimental results show that osimertinib mesylate can significantly enhance the antibacterial activity of polymyxin against multidrug-resistant Gram-negative bacteria, effectively reduce the minimum inhibitory concentration of polymyxin, thereby reducing the clinical dosage of polymyxin and lowering the risk of its inherent nephrotoxicity and neurotoxicity. Furthermore, this invention reveals that the combined use of osimertinib mesylate and polymyxin can delay or reverse bacterial resistance to polymyxin, improve the survival rate of infected animal models, and broaden the antibacterial spectrum.