135 results about "Osimertinib" patented technology

The invention relates to the technical field of medical data analysis, in particular to a lung adenocarcinoma osimertinib drug resistance prediction model construction method and system based on machine learning. Clinical data of lung adenocarcinoma patients and mRNA (messenger ribonucleic acid) data of a public database are integrated, after Mann-Wh itney U inspection, FPKM standardization and other preprocessing are carried out, XGBoost is utilized to construct a basic model driven by clinical indexes, a prognosis model driven by gene characteristics is constructed through R packet Mime, and TYMS and UAP1L1 are screened out to serve as key genes. The performance of the model is optimized through residual correction and stacking integration, and finally the AUC is improved to 0.924. Serum RNA (Ribonucleic Acid) detection and verification show that TYMS and UAP1L1 are remarkably and highly expressed in a drug-resistant group. According to the method, traditional biopsy is replaced with noninvasive serum detection, the detection cost is reduced, the model generalization ability is verified through an independent queue, and an efficient and accurate solution is provided for early warning and personalized treatment of osimertinib drug resistance of the lung adenocarcinoma patient.

Disclosed is an anticancer composition using a flavone derivative. In the present invention, the flavone derivative exhibits cytotoxicity against: H827, H1299, H522, and A549, which are human non-small cell lung cancer cell lines; MCF-7, which is a human breast cancer cell line; and PANC-1, which is a human pancreatic cancer cell line, in a time-dependent manner and in a treatment concentration-dependent manner, and not only exhibits a synergistic effect when used in combination with other conventional anticancer agents, such as osimertinib, which is an anticancer agent targeting for lung cancer, tamoxifen, which is a hormone agent against breast cancer, and gemcitabine, which is a cytotoxic anticancer agent against pancreatic cancer, but also exhibits the effect of synergistically inhibiting the expression of HIF-1α when used alone or in combination with an existing anticancer agent.

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 present specification relates to an improved process for producing osimertinib. [Formula 1] TIFF2025511404000023.tif36160

The invention provides application of tipirfarb in reversing osimertinib drug resistance, and relates to the technical field of medicines. The research of the inventor finds that the high expression of the MAST1 protein induces the targeted drug resistance of lung cancer, and the MAST1 protein can be used as an anti-drug-resistance action target. A new MAST1 inhibitor tipirfarb is obtained through virtual screening, and the antitumor activity of osimertinib on drug-resistant cells can be enhanced. The invention lays a foundation for subsequent development of an MAST1-targeted anti-drug-resistance strategy, provides brand new anti-drug-resistance targets and candidate molecules for targeted therapy of lung cancer, and has clinical value.

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 relates to an iRGD modified dual drug-loading liposome and an application of the iRGD modified dual drug-loading liposome in radiotherapy sensitization of targeted glioblastoma. The liposome is composed of HSPC, CHO-HP, DSPE-mPEG2000, and DSPE-PEG2000-MAL, and is loaded with Osimertinib (Osimertinib) and Bortezomib (Bortezomib) through a pH (Potential of Hydrogen) gradient method, and the preparation method of the liposome comprises the following steps: carrying out a reaction on the Osimertinib (Osimertinib) and the Bortezomib (Bortezomib) in the presence of a Osimertinib is used as an EGFR inhibitor, bortezomib is used as a proteasome inhibitor, and osimertinib and bortezomib synergistically enhance the radiotherapy sensitivity by weakening the DNA repair capability of tumor cells. The iRGD peptide on the surface of the liposome is combined with tumor cell specific receptors alpha v beta 3 and NRP1 in a targeting manner, so that the liposome is mediated to pass through tumor neovascularization and efficiently deliver drugs to tumor parts. Animal experiment results show that the enrichment of the liposome in tumor tissues is obviously higher than that of common liposome, and the drug release has good controllability. Compared with the prior art, the invention has obvious advantages in tumor targeting, drug delivery efficiency and radiotherapy sensitization effect, is suitable for combined treatment of radiotherapy drug-resistant glioblastoma, and has a wide clinical application prospect.

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 invention deals with a novel process for preparation of the pharmaceutically useful product Osimertinib of formula (1).

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.

The present invention relates to the field of biomedicine, and more specifically to the use of berbamine in the preparation of a drug combination for treating drug-resistant non-small cell lung cancer. Berbamine can reverse osimertinib resistance in non-small cell lung cancer, rendering osimertinib, which was previously ineffective or ineffective in treating drug-resistant non-small cell lung cancer, effective or highly effective. Berbamine reverses osimertinib resistance in non-small cell lung cancer in vivo or in vitro, with manifestations of reversal of resistance including significant inhibition of proliferation of drug-resistant non-small cell lung cancer cell lines, significant promotion of apoptosis of drug-resistant non-small cell lung cancer cell lines, and significant inhibition of proliferation of drug-resistant non-small cell lung cancer cells in vivo.

The invention discloses a medicine for preventing or treating liver toxic and side effects of osimertinib, and belongs to the technical field of medicines. Aiming at liver toxic and side effects caused by osimertinib, the invention provides an effective therapeutic drug, and the autophagy inhibitor relieves death caused by excessive activation of an autophagy pathway in hepatocytes by inhibiting autophagy activated by osimertinib, so that hepatotoxicity caused by osimertinib is relieved. The autophagy inhibitor and osimertinib are combined, so that the survival rate of hepatocytes can be remarkably improved, and liver injury caused in the osimertinib treatment process is reduced. The invention further provides novel application of the hydroxychloroquine or the S-adenosylmethionine in preparation of the medicine for preventing or treating the liver toxic and side effects of the osimertinib, the hydroxychloroquine or the S-adenosylmethionine has a remarkable treatment effect on liver injuries caused by the osimertinib, the medication safety of the hydroxychloroquine or the S-adenosylmethionine is high, and the hydroxychloroquine or the S-adenosylmethionine can be used for preparing the medicine for preventing or treating the liver toxic and side effects of the osimertinib. Good development prospects are realized.

The invention relates to a body resistance strengthening and stagnation eliminating prescription for resisting non-small cell lung cancer and a preparation method thereof. The body resistance strengthening and stagnation eliminating prescription is prepared from the following raw material medicines in parts by weight: 2-50g / part of radix fici simplicissimae, 2-50g / part of radix pseudostellariae, 2-50g / part of poria cocos, 2-50g / part of rhizoma atractylodis macrocephalae, 2-50g / part of radix scutellariae, 2-50g / part of oldenlandia diffusa, 2-50g / part of radix ranunculi ternati, 2-50g / part of polygonum cuspidatum, 2-50g / part of curcuma zedoary, 2-50g / part of oyster, 2-50g / part of platycodon grandiflorum, 2-50g / part of edible tulip and 2-50g / part of sculellaria barbata. Cell tests and construction of an NSCLC osimertinib-resistant animal model prove that the body resistance strengthening and stagnation eliminating prescription can regulate a tumor microenvironment (TME) and inhibit growth of osimertinib-resistant non-small cell lung cancer cells. In addition, the formula for strengthening the body resistance and removing stasis can also inhibit growth of common non-small cell lung cancer cells. Meanwhile, clinical observation finds that the body resistance strengthening and stasis removing prescription can improve symptoms such as insomnia, rash and diarrhea of patients with lung accumulation (lung cancer and pulmonary nodule), and improve the life quality of the patients.

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.

The invention discloses application of a preparation capable of improving glutathione concentration in reversing osimertinib drug resistance. The invention also discloses a pharmaceutical composition for treating the drug-resistant lung cancer, and the pharmaceutical composition comprises a preparation capable of improving the concentration of glutathione (GSH) and osimertinib (AZD9291). The invention finds that the combination of GSH and AZD9291 has a synergistic effect, the combination of 3mM GSH and 1 mu M osimertinib can inhibit the proliferation of non-small cell lung cancer, the inhibition rate is significantly higher than that of the single use of AZD9291, and the combination of GSH and osimertinib has a synergistic inhibition effect on AZD9291 drug-resistant NSCLC cells. Meanwhile, the intracellular lipid peroxidation level of lung cancer cells is remarkably improved through GSH treatment, and the treatment effect of AZD9291 on NSCLC is enhanced.

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 present invention relates to a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL S-PAC-PEG S) micelle in which osimertinib, etoposide, and docetaxel are encapsulated, and used thereof. Specifically, the present invention relates to a pharmaceutical composition for preventing or treating cancer, wherein osimertinib, which is a target therapeutic agent, and etoposide and docetaxel, which are both anticancer chemotherapeutic drugs, are encapsulated in a Soluplus® polymer to form micelles, whereby anticancer activity can be effectively induced through an improvement in the solubility of the poorly soluble drug in water and a synergistic action between the drugs. The pharmaceutical composition for cancer treatment according to the present invention enables effective solubilization of osimertinib, etoposide, and docetaxel by encapsulating the poorly soluble drugs in micelles formed using the PCL-PVAc-PEG (Soluplus®) polymer, and thus can be advantageously used as an intravenous injection. With the advantage of avoiding first-pass metabolism in the liver, unlike oral dosage forms, intravenous injection can reduce unnecessary loss of drugs and also increase bioavailability compared to oral dosage forms, and thus is an effective administration method capable of expecting a high effect with the same amount of drugs. Therefore, development of such a formulation allows effective administration of osimertinib, etoposide, and docetaxel. In addition, the composition of the present invention can effectively treat non-small cell lung cancer having an EGFR-sensitive mutation while preventing the development of anticancer drug resistance, which can be caused by single drug administration, by using a targeted therapeutic agent and chemotherapy in combination. Furthermore, the composition of the present invention employs a biocompatible polymer as a material of the micelle and thus has an advantage of being safe for the human body. Moreover, by combining osimertinib, etoposide, and docetaxel at a specific molar ratio and encapsulating same in Soluplus® micelles, the composition of the present invention has excellent encapsulation efficiency of three kinds of drugs and has high monodispersibility having a consistent particle size of 50-60 nm. Thus, the composition can maintain consistent product quality and has excellent formulation stability.

The invention discloses 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 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.