45 results about "Gefitinib" patented technology

The invention discloses a biotinylated gefitinib probe as well as a preparation method and application thereof, the biotinylated gefitinib probe is better in stability and high in sensitivity and accuracy, can be stored for a long time, and can be used in experiments needing long-time storage and multiple analysis; the kit can also be used for detecting the binding condition of gefitinib and EGFR under various conditions so as to treat or diagnose cancers; the EGFR mutation type is determined in combination with gene sequencing, the feasibility and effectiveness of the gefitinib for treating the EGFR mutation type can be evaluated, and medication is guided. Therefore, the biotinylated gefitinib probe is expected to become an indispensable tool in precision medical treatment, and more patients are benefited from gefitinib treatment.

The present invention relates to a method for treating gefitinib and / or erlotinib resistant cancer. Cancer patients are monitored for cancer development after treatment with gefitinib and / or erlotinib. The development of cancer indicates that the cancer is resistant to gefitinib and / or erlotinib. Once it is shown that the cancer is developing, a pharmaceutical composition containing an irreversible epidermal growth factor receptor (EGFR) inhibitor is administered to the patient. In a preferred embodiment, the irreversible EGFR inhibitor is EKB-569, HKI-272 and HKI-357.

The invention discloses a kit for simultaneously determining five liver cancer multi-kinase targeted drugs and active metabolites thereof based on LC-MS / MS. The kit comprises an internal standard solution, a standard substance solution, a protein precipitant and a solution used as a mobile phase, the internal standard solution is a gefitinib solution; the standard substance solution is a solution of sorafenib, sorafenib nitric oxide, lenvatinib, lenvatinib nitric oxide, dorafenib, dorafenib nitric oxide, regorafenib, regorafenib nitric oxide, cabozatinib and cabozatinib nitric oxide; the protein precipitant is an ice acetonitrile solution; the mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A is an aqueous solution containing formic acid, and the mobile phase B is an acetonitrile solution containing formic acid. The invention also discloses a method for determining the liver cancer multi-kinase targeted drug and the active metabolite thereof. The method can be used for monitoring drug concentration and preparing a drug time monitoring curve, and can simultaneously improve the sensitivity and selectivity of the method and shorten the analysis time so as to improve the analysis flux.

The application discloses a fluorescence enhancement anchor agent based on a fluoroboron dipyrrin-tetrazine dye for inflation microscopy technology, and belongs to the technical field of biochemical analysis. The fluorophore of the fluorescence enhancement anchor agent is shown in formula (I), formula (II) or formula (III): the tetrazine group carried by the fluorescence enhancement anchor agent is removed from fluorescence quenching through a biological orthogonal reaction with a drug probe, and the drug probe is shown in formula (IV): the fluorescence enhancement anchor agent can covalently and non-covalently anchor small molecules in a hydrogel network based on a tetrazine biological orthogonal reaction, and realizes inflation microscopic fluorescence imaging of a double fluorescence enhancement mechanism. In addition, the drug probe selects a non-covalent drug, gefitinib, as a probe core, is modified with a BCN click handle, and successfully realizes in-situ fluorescence inflation microscopic imaging of an EGFR drug-target, thereby providing a new tool for research and clinical research on non-covalent drug target co-localization information of exosomes.

The present invention belongs to the field of chemical medicine and discloses an EGFR proteolysis-targeted chimera, its preparation method, pharmaceutical composition, and application. The present invention provides an EGFR-degradable proteolysis-targeted chimera based on CP0371, a novel E3 ligase ligand with "molecular glue" functionality, and gefitinib, a target protein ligand. The EGFR proteolysis-targeted chimera prepared by the present invention can effectively induce EGFR degradation in cancer cell lines and has considerable bioavailability. It can be used to prepare EGFR inhibitors and can be used to form pharmaceutical compositions. It has a certain inhibitory effect on the proliferation of various tumor cells and is suitable for the development of cancer drugs for the treatment of colorectal cancer, lung cancer, esophageal cancer, glioblastoma, anal cancer, head and neck epithelial cancer, and other cancers.

Disclosed are methods of treating cancer with a tri-agent therapy. The methods include a cancer treatment regimen with two or three different antineoplastic medications, including tamoxifen, gefitinib, and vinorelbine (TGV). The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen, gefitinib, and vinorelbine. The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen and gefitinib as adjuvants to a prescribed treatment. The cancer treatment regimen can be cyclical or can be a continuous metronomic treatment with metronomic dosing. The cancer treatment regimen can be cyclical and then can be followed by a continuous metronomic treatment with metronomic dosing.

The invention discloses a fluorescence enhancement anchoring agent based on a BODIPY-tetrazine dye for an expansion microimaging technology, and belongs to the technical field of biochemical analysis. A fluorophore of the fluorescence enhanced anchoring agent is shown as a formula (I), a formula (II) or a formula (III): # imgabs 0 # imgabs 1 #; a tetrazine group carried by the fluorescence enhanced anchoring agent and a drug probe are subjected to a biological orthogonal reaction to remove fluorescence quenching; the drug probe is shown as a formula (IV): # imgabs2. The fluorescence enhancement anchoring agent can anchor covalent and non-covalent small molecules in a hydrogel network based on tetrazine biological orthogonal reaction, and meanwhile, expansion microscopic fluorescence imaging of a dual fluorescence enhancement mechanism is realized. Besides, according to the drug probe, a non-covalent drug gefitinib is selected as a probe core, a BCN click handle is modified, in-situ fluorescence expansion microscopic imaging of EGFR drug-target is successfully achieved, and a new tool is provided for non-covalent drug target co-localization information research and clinical research of exosomes.

The invention relates to application of a combination of STM2457 and gefitinib in preparation of a medicine for preventing and treating lung cancer, and belongs to the technical field of biological medicines. The invention provides an application of an METTL3 inhibitor and gefitinib in preparation of a medicine for preventing and treating lung cancer. In a cell experiment, the expression of METTL3 is inhibited and then Gefitinib is used, so that the killing effect of the Gefitinib on lung cancer cells is promoted, and the drug resistance of the lung cancer cells on the Gefitinib is reduced. The small molecule inhibitor STM2457 of the METTL3 and the Gefitinib are combined for medication, so that the killing effect on cancer cells can be synergistically improved. In a mouse experiment, compared with a single drug, the drug combination has the advantages that the growth of tumors is more effectively inhibited, the lymph node metastasis of lung cancer cells can be effectively prevented, no obvious side effect exists, and a good treatment effect is shown. Therefore, the drug combination of the METTL3 inhibitor and the Gefitinib has a remarkable treatment effect on the NSCLC.

This invention provides hepatocellular carcinoma-derived growth factor (HDGF) as a target for resistance to tyrosine kinase inhibitors and its related applications. This invention provides the application of HDGF as a target in screening and / or preparing drugs that can improve resistance to tyrosine kinase inhibitors in patients. This invention discovers that high expression of HDGF is one of the mechanisms of resistance to molecularly targeted drugs such as gefitinib and other tyrosine kinase inhibitors. Targeting HDGF can effectively improve resistance to gefitinib in NSCLC and enhance therapeutic efficacy.

This invention relates to a small-molecule fluorescent photosensitizer containing a gefitinib backbone structure and an AIE group, its preparation, and its application, belonging to the field of fluorescent photosensitizer technology. The fluorescent photosensitizer includes an AIE group, a linking group, and a recognition group. On one hand, the AIE group backbone structure consists of a pyridine cation (electron acceptor, A), an ethylene group (π-bridge), a thiophene fragment (π-bridge and electron donor, D), and a triphenylamine segment (D), which is a typical D-π-A molecular configuration, thus exhibiting near-infrared fluorescence emission. On the other hand, by introducing heavy atoms to enhance the spin-orbit coupling of the photosensitizer, the efficiency of singlet oxygen generation is improved. The fluorescent photosensitizer can precisely target EGFR-overexpressing non-small cell lung cancer cells without illuminating normal cells. The fluorescent photosensitizer exhibits aggregation-induced emission properties, avoiding the ACQ effect during aggregation, greatly improving the ROS generation efficiency and promoting its tumor-killing effect.

The invention discloses an application of plant lactobacillus GOLDGUT-HNU082 in relieving side effects of tumor drugs, and the preservation number of the plant lactobacillus GOLDGUT-HNU082 is CGMCC (China General Microbiological Culture Collection Center) NO.33075. The invention further discloses a preparation method of the plant lactobacillus GOLDGUT-HNU082. The bacterium can obviously relieve liver and intestinal injury caused by gefitinib, and the liver and intestinal injury shows that liver transaminase is reduced, inflammatory markers are reduced, and liver and intestinal tissue structures are more complete. In addition, the bacterium also remarkably improves the generation of short-chain fatty acid, and the regulation effect of the bacterium on the intestinal microecology is further proved. The research aims at exploring the relieving mechanism of probiotic mediated intestinal flora on the side effect of the medicine, promoting the probiotics to become an accompanying product of the gefitinib medicine, remarkably improving the side effect of the medicine and reducing the psychological burden of a patient to take the medicine.

This invention discloses the application of fruquintinib combined with PD-1 monoclonal antibody in maintenance therapy for HER-2 negative advanced gastric cancer / geoesophageal junction adenocarcinoma, belonging to the field of tumor treatment technology. This invention targets HER2-negative advanced gastric cancer or gastroesophageal junction adenocarcinoma, specifically patients who achieve disease control after 3 months of first-line induction therapy with PD-1 monoclonal antibody combined with oxaliplatin, followed by maintenance therapy with fruquintinib combined with PD-1 monoclonal antibody without chemotherapy. The maintenance therapy regimen provided by this invention improves patients' quality of life and prolongs overall survival while delaying disease progression, and has significant clinical implications.

The present invention belongs to the field of biotechnology and discloses an orally-administered gefitinib complex with enhanced anti-cancer effects, as well as its preparation method and application. The gefitinib complex of the present invention is formed by combining at least one of nicotinamide and 3-aminothioamino-butyric-2-one oxime with gefitinib or a pharmaceutically acceptable salt thereof. The present invention also provides the use of the gefitinib complex in the preparation of a drug for the prevention and / or treatment of lung cancer, particularly in the preparation of a drug for the prevention and / or treatment of non-small cell lung cancer. The gefitinib complex of the present invention has significantly improved solubility and dissolution rate, exhibiting enhanced therapeutic effects on cancer; it can increase its uptake by cancer cells, exhibiting a stronger ability to inhibit cancer cell proliferation, and has a better anti-cancer effect.

The invention provides an SLC16A3 inhibitor based on ferroptosis regulation and application of the SLC16A3 inhibitor in lung adenocarcinoma, and relates to the technical field of biological treatment drugs. The SLC16A3 inhibitor is a drug MSC-4381, the drug MSC-4381 is an effective SLC16A3 inhibitor, the SLC16A3 inhibitor can be used for inhibiting lactic acid transporter SLC16A3, breaking the redox steady state of tumor cells, inducing ferroptosis and remarkably enhancing the curative effect of the drug gefitinib, and in an in-vivo and in-vitro model, cell proliferation, migration and invasion can be inhibited through SLC16A3 knock-down or pharmacological inhibition, so that the SLC16A3 inhibitor can be used for preventing and treating the tumor cells. The MSC-4381 and the gefitinib are combined to promote lipid peroxidation and iron ion accumulation, the tumor growth can be obviously delayed through drug combination of the MSC-4381 and the gefitinib, the effect can be partially reversed through the Ferrostatin-1, the ferroptosis-dependent mechanism of the MSC-4381 and the gefitinib is verified, and transcriptional regulation and control of the SLC16A3 by the HIF1A and influence on ferroptosis resistance are clear. The invention provides a feasible combined medication strategy, verifies the significant tumor inhibition effect of the HIF1A-SLC16A3 axis in cell and animal models, reveals the key effect of the HIF1A-SLC16A3 axis in lung adenocarcinoma drug resistance formation, and provides a new combined treatment strategy and a new molecular target.

Disclosed are methods of treating cancer with a tri-agent therapy. The methods include a cancer treatment regimen with two or three different antineoplastic medications, including tamoxifen, gefitinib, and vinorelbine (TGV). The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen, gefitinib, and vinorelbine. The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen and gefitinib as adjuvants to a prescribed treatment. The cancer treatment regimen can be cyclical or can be a continuous metronomic treatment with metronomic dosing. The cancer treatment regimen can be cyclical and then can be followed by a continuous metronomic treatment with metronomic dosing.

The invention discloses a series of 3-(2-aminobenzo [d] thiazole-5-yl) benzamide derivatives as well as a preparation method and application thereof, and relates to the technical field of organic medicine synthesis. According to the 3-(2-aminobenzo [d] thiazole-5-yl) benzamide derivatives, a benzimidazole part of an existing benzimidazole substituted quinazolinone derivative is replaced with benzothiazole, quinazolinone is replaced with benzamide, and a series of 3-(2-aminobenzo [d] thiazole-5-yl) benzamide derivatives are prepared. The derivatives not only can effectively inhibit ROR1 and downstream pathways thereof so as to induce G1 phase retardation and apoptosis of tumor cells, but also can significantly inhibit migration and invasion of the tumor cells. In addition, the selectivity of the derivatives to tumor cells is also greatly improved, and better safety is shown; the sensitivity of chemotherapeutic drugs such as paclitaxel (tylosin) and doxorubicin (doxorubicin) and EGFR (epidermal growth factor receptor) targeted drug gefitinib to drug-resistant cells can also be enhanced, and the derivative disclosed by the invention shows a relatively strong synergistic curative effect when being combined with the anti-tumor drug.

The present invention provides a drug for treating non-small cell lung cancer, belonging to the field of medicine. The drug's raw materials include gefitinib and andrographolide, wherein the concentration of gefitinib is 12-20 μM and the concentration of andrographolide is 200-250 μM. The drug is in the form of an oral liquid preparation or an oral tablet. Experimental results show that the drug provided by the present invention has a significant inhibitory effect on the expression of apoptosis-related proteins and genes in PC9 / G cells, with a greater inhibitory effect than gefitinib or andrographolide alone, indicating a certain synergistic relationship between the two.

The application discloses a composite nano-silicon ball drug delivery system and a preparation method and application thereof. The system takes mesoporous silica nanoparticles as a carrier, loads gefitinib, and is coated with a PD-L1 antibody modified platelet membrane on the surface. The application prepares a composite multifunctional mesoporous silica nanoparticle which loads gefitinib and is coated with a PD-L1 antibody modified platelet membrane on the surface, so that the composite multifunctional mesoporous silica nanoparticle can be directed to reach a tumor surgery blood vessel damage site, kill residual tumor cells, reduce matrix hardness in the microenvironment, enhance the permeability and toxicity of immune cells, the two effects are interdependent and mutually enhanced, and the application overcomes the invalidity of colorectal tumor immunotherapy and prolongs the survival period of patients.

The invention discloses a macrocyclic cytochalasin derivative as well as a preparation method and application thereof. The macrocyclic cytochalasin derivative comprises the macrocyclic cytochalasin derivative disclosed by the invention, and the macrocyclic cytochalasin derivative can obviously inhibit the proliferation of non-small cell lung cancer (H1975), and the inhibitory activity of part of compounds obviously exceeds that of positive control gefitinib. Wherein the efficacy of the compound 8 is equivalent to that of cis-platinum in H1975 cells, the efficacy of the compound 8 is better in HCC827 cells, and the toxicity of the compound 8 to normal cells is lower than that of the cis-platinum.

Provided are an shRNA for reversing EGFR-TKI drug resistance in non-small cell lung cancer and use thereof, belonging to the fields of molecular biology and biomedicine. By using the designed shRNA, the expression of the KLHL22 gene is targeted and inhibited, and the nucleotide sequence of the shRNA is set forth in SEQ ID No. 1-SEQ ID No. 2. It is found by means of in vivo experiments that targeted inhibition of KLHL22 expression can effectively reverse the drug resistance of NSCLC cells to EGFR-TKI. In in vitro cell experiments, inhibition of KLHL22 expression significantly improves the sensitivity of drug-resistant NSCLC cells to gefitinib, thereby restoring the anti-tumor effect of the drug. This innovative strategy provides a new direction for overcoming EGFR-TKI drug resistance, and has important clinical application prospects.

The invention relates to a pharmaceutical composition for treating cancers (Ligusticum wallichii series) as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition comprises a ginseng extract, a coix seed extract and a marsdenia tenacissima extract. The pharmaceutical composition disclosed by the invention has a synergistic effect in the aspect of treating cancers, can still have a synergistic effect when being combined with mannatide and berberine hydrochloride, and also has a synergistic effect and toxicity reducing effect when being combined with cis-platinum or gefitinib.

The invention belongs to the technical field of biological medicine, and particularly relates to application of tasilimus in preparation of a product for overcoming drug resistance of non-small cell lung cancer. The invention finds that the combined use of the first generation (gefitinib) and the third generation (osimertinib) EGFR-TKI can significantly reduce the tolerance degree of EGFR-TKI drug-resistant cells to the two drugs. In a nude mouse model experiment, the curative effect of the combination of the tasilisib and the osimertinib is obviously superior to that of the single use of the osimertinib or the combination of the osimertinib and the LY294002, the obvious tumor growth inhibition effect is shown, and the drug-resistant relapse of tumors can be effectively delayed. Different from other PI3KCA inhibitors, the enhancement of the EGFR-TKI targeted therapy effect of the tasilimus does not depend on the inhibition of a PI3K / AKT pathway, but recovers the sensitivity of the drug-resistant cells to the EGFR-TKI by awakening the dormant state of the tumor, thereby providing a new thought for a therapeutic scheme.

The present invention discloses a preparation method and application of gefitinib-hesperetin nano-cocrystals, belonging to the field of pharmaceutical technology. The gefitinib-hesperetin co-crystals and a stabilizer are placed in a grinding jar, ultrapure water is added, and ultrasound is applied until the gefitinib-hesperetin co-crystals and the stabilizer are evenly dispersed. Grinding beads are added, the rotation speed is adjusted, and the gefitinib-hesperetin nano-cocrystals are obtained after grinding. The present invention takes gefitinib as the research object and hesperetin as the co-crystal former, and successfully obtains gefitinib-hesperetin nano-cocrystals by combining crystal engineering and nanotechnology. The structure and physicochemical properties of the gefitinib-hesperetin co-crystals are characterized by a series of solid characterization techniques, and its in vitro dissolution, in vitro anti-tumor activity, and in vivo bioavailability in rats are systematically evaluated. It is shown that the gefitinib-hesperetin nano-cocrystals not only effectively improve the solubility and bioavailability of gefitinib, but also enhance the anti-tumor activity of the drug.

The present invention belongs to the technical field of crystalline drug molecules, and specifically relates to a co-crystal of gefitinib. The present invention provides a gefitinib-chrysin co-crystal, a gefitinib-ketorolac co-crystal, a 2-indolecarboxylic acid-gefitinib co-crystal and a preparation method thereof. The gefitinib co-crystal of the present invention has excellent physical and chemical properties, high purity, good stability, and high solubility, and is helpful to improve the bioavailability of gefitinib and improve clinical efficacy. The preparation method is simple and efficient, and is suitable for industrial production.

The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

The invention belongs to the technical field of pharmaceutical chemistry, and particularly discloses a gefitinib intermediate impurity YKYZ-C-GF-3 and a preparation, analysis and control method thereof, the name of the impurity is 8-chlorine-N-(3-chloro-4-fluorophenyl)-6-hydroxy-7-methoxyquinazoline-4-amine, the molecular formula is C15H10Cl2FN3O2, the molecular weight is 354.14, and the structure is confirmed by mass spectrum, 1H-NMR and 13C-NMR. The impurity is generated by the reaction of sulfonyl chloride in thionyl chloride, the structure of the impurity is similar to that of a gefitinib intermediate, and the impurity is difficult to remove by a general method, so that the invention provides a method for treating thionyl chloride by using activated carbon to reduce the content of sulfonyl chloride in thionyl chloride from the source, thereby reducing the generation of the impurity. And the quality of the final gefitinib finished product is ensured.

The invention discloses a polypeptide for inhibiting lung adenocarcinoma metastasis and application thereof, belongs to the technical field of biology, and aims to solve the problems that lung adenocarcinoma cells in the prior art have very strong invasion and migration ability, and non-small cell lung cancer patients with high expression of NSUN2 easily generate drug resistance to gefitinib drugs. The amino acid sequence of the polypeptide for inhibiting lung adenocarcinoma metastasis is as shown in a general formula X-RHTQIRPTMFPPY; x at the N terminal in the general formula represents a modification group, and Y at the tail represents a cell-penetrating peptide; the invention is suitable for preparing a therapeutic reagent for lung cancer, and can achieve the effect of inhibiting the methylation modification of NSUN2 so as to inhibit the metastasis of lung adenocarcinoma.

The application discloses a kind of biotinylated gefitinib probe and its preparation method and application, the probe described in the application is better in stability, sensitivity and accuracy are high, can be long-term preserved, can be used in the experiment needing long time preservation and multiple analysis;It can also be used to detect the binding condition of gefitinib and EGFR in various situations, treat or diagnose cancer;Determine the EGFR mutation type in combination with gene sequencing, the feasibility and effectiveness of the treatment of gefitinib to the EGFR mutation type can also be evaluated, guide drug use.Therefore, biotinylated gefitinib probe is expected to become indispensable tool in precision medicine, so that more patients benefit from gefitinib treatment.

The invention discloses an application of a formononetin derivative containing benzyl piperidine in preparation of a medicine for inhibiting breast cancer MDA-MB-231 cells. All target compounds have certain in-vitro inhibitory activity on MDA-MB-231 at the concentration of 1 mu M and 10 mu M. Wherein under the concentration of 10 mu M, except H22, the inhibitory activity of other compounds is far higher than that of gefitinib.

The present invention relates to the treatment of cancer and particularly of lung cancer. In the present study, the inventors analyzed the role of the Notch pathway in EGFR-driven lung adenocarcinoma (LUAD) using complex genetic mouse models and patient derived xenografts. They found that, similarly to KRAS-driven LUAD, EGFR-driven LUAD shows both Notch pathway hyperactivation and addiction to its activity. Importantly, combination of EGFR tyrosine Kinase Inhibitors (TKIs) with Notch inhibition re-sensitizes LUAD cells harboring gatekeeper mutations EGFRT790M or EGFRC797S to gefitinib and osimertinib, respectively. Moreover, they show that pSTAT3, which is known to increase upon EGFR TKI treatment, directly binds to the HES1 promoter and represses HES1 expression. Finally, high HES1 expression levels correlate with shorter progression free survival and its expression increases upon progression in EGFR mutated patients under TKI treatment. Thus, the present invention relates to a combination of a tyrosine-kinase inhibitor (TKI) against epidermal growth factor receptor (EGFR) and an inhibitor of the Notch signalling pathway for use in the treatment of a cancer in a subject in need thereof.