1686 results about "Anti neoplastic" patented technology

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and Ly2090314 and application of the pharmaceutical composition. According to the invention, the Ly2090314 and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

The invention relates to the field of natural products, in particular to a dimer compound of guaiane type sesquiterpenes and uric acid as well as an extraction and separation method and application of the dimer compound. According to the invention, a new dimer compound of guaiane type sesquiterpene and uric acid is extracted and separated from carpesium abrotanoides in Guizhou, and it is found that the dimer compound has relatively strong anti-tumor activity. The compound has strong inhibitory activity on breast cancer, prostate cancer, nasopharynx cancer, liver cancer, lung cancer, leukemia, pancreatic cancer, glioma, osteosarcoma, skin cancer, cervical cancer, ovarian cancer, kidney cancer and esophageal cancer, and provides an optional scheme for broad-spectrum anti-cancer drugs. Moreover, in human prostate cancer cells PC3, human cervical cancer cells Hela, human liver cancer cells HepG2 and human glioma cells U87 which are resistant to paclitaxel, the compound also shows strong anti-cancer activity, which indicates that the compound has the potential of treating patients resistant to paclitaxel.

The invention discloses application of camellia nitidissima exosome-like nano-vesicles in preparation of antitumor drugs, and belongs to the technical field of biological medicines. The exosome-like nano-vesicles are extracted from golden camellia for the first time, and the exosome-like nano-vesicles are proved to have remarkable anti-tumor activity.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

The invention belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a cascade response type nano-particle with a microenvironment remodeling function and a preparation method and application of the cascade response type nano-particle. The nanoparticle provided by the invention adopts a bionic hybrid membrane engineering strategy: an inner core is formed by loading an exosome inhibitor on a nano material, and the surface is covalently coupled with M2 type macrophage specific targeting peptide; the outer layer coats a macrophage membrane and active oxygen response type liposome composite membrane layer through a co-extrusion technology, and is loaded with a TLR agonist. Animal experiments show that after being injected through caudal vein, the nano-particles are enriched at a tumor site in a targeted manner through homing receptors such as membrane surface integrin alpha4beta1 and the like, and outer membrane cracking is triggered in a high-ROS tumor microenvironment, so that space-time controlled release of a TLR agonist and targeted phagocytosis of an exosome inhibitor by macrophages guided by a targeted peptide are realized. The anti-tumor synergistic effect is achieved through multiple regulation and control mechanisms, and an effective treatment strategy is provided for tumor immunotherapy.

To provide an antitumor drug having an excellent therapeutic effect, which is excellent in terms of antitumor effect and safety. Provided is an anti-cadherin 17 antibody comprising a heavy chain variable region and a light chain variable region, a drug conjugate thereof, and a composition containing the anti-cadherin 17 antibody or the drug conjugate thereof, and an application thereof as a drug.

The preparation method comprises the following steps: synthesizing gold nanostars (GNS) by using a seed growth method, coating mesoporous cerium dioxide (mCeO2) by using a template method, and loading a photosensitizer indocyanine green (ICG), so as to form a nano enzyme diagnosis and treatment system with chemical activity, photoactivity and photothermal effects. In the system, the gold nanostars have a good photo-thermal effect due to the multi-branched structure of the gold nanostars; on one hand, the mesoporous cerium dioxide coated on the outer layer has a chemical effect due to the nano-enzyme effect, and on the other hand, the mesoporous structure of the mesoporous cerium dioxide can better load the photosensitizer indocyanine green. All the components have good stability and biological safety, also have peroxidase simulation activity and a drug loading function, can improve the level of reactive oxygen species (ROS) in a tumor microenvironment and load photosensitizer drugs, and have an excellent anti-tumor effect and small side effects.

The invention provides a whole-process targeting polypeptide, a drug compound thereof, a drug delivery system and application of the whole-process targeting polypeptide. The whole-process targeting polypeptide comprises pHA and VAP which are covalently connected through a bridging structure; the VAP is LVAP, a reverse sequence polypeptide of the LVAP, DVAP or SVAP; wherein the amino acid sequence of the LVAP is as shown in SEQ ID NO: 1; the SVAP is a D-configuration polypeptide of the LVAP; the DVAP is a D-configuration polypeptide of the LVAP inverted sequence polypeptide; the bridging structure is amino-monoethylene glycol-carboxylic acid or a derivative thereof. The whole-process targeting polypeptide not only can cross a blood-brain barrier, target tumor neovascularization, cross a blood-tumor barrier, target tumor mimicry vessels, tumor cells and stem cells thereof, but also has better tumor cell affinity, anti-tumor treatment and in-vivo safety effects. Meanwhile, the drug compound or the drug delivery system has a synergistic effect after being combined with a chemotherapeutic drug, and the anti-tumor drug effect can be remarkably improved.

The application describes the first-in-human study on using a anti-KLK2xCD3 bispecific antibody and another anti-cancer drug, in particular, in particular a taxane chemotherapy or Androgen Receptor Pathway Inhibitor (ARPI), to provide enhanced antitumor efficacy with a deeper and more durable clinical response.

The invention provides a gamma delta T cell preparation as well as a preparation method and application thereof, and belongs to the technical field of T cells. The liposome is prepared from the following raw materials in parts by weight: 15-20 parts of modified gamma delta T cell liposome, 1-3 parts of cell stimulating factors and 4-7 parts of culture medium freeze-dried powder, the modified gamma delta T cell lipidosome is prepared by embedding gamma delta T cells through lipidosome, coupling with acetylenic bond modified chitosan, and further mixing with MFAP4 protein and b4GALT1 protein. The culture medium freeze-dried powder is prepared by freeze-drying the culture medium in the engineering culture process of gamma delta T cells, and the cell stimulating factors are resveratrol and quercitrin. According to the gamma delta T cell preparation prepared by the invention, the survival ability and resistance of gamma delta T cells are improved, the anti-tumor activity of the gamma delta T cells is improved, and the gamma delta T cell preparation has relatively good antioxidant and anti-inflammatory effects, reduces the inhibition of inflammation on an immune system and has a very good treatment effect on pancreatic ductal adenocarcinoma.

The invention discloses a preparation method of a doxorubicin-loaded ginseng selenium polysaccharide nano-carrier with immunoregulation and liver cancer cell inhibition functions, and aims to solve the problems of toxic injury of tissues and organs and inhibition of an immune system caused by an antitumor drug doxorubicin. According to the invention, deoxycholic acid is grafted on the ginseng selenium polysaccharide, so that the ginseng selenium polysaccharide is hydrophobized and forms an amphiphilic polysaccharide polymer, and the limitations of large molecular weight, low bioavailability and the like of the ginseng selenium polysaccharide are overcome. The self-assembled ginseng selenium polysaccharide nanoparticles are used as carriers for delivering antitumor drugs, so that the self-assembled ginseng selenium polysaccharide nanoparticles have an immunoregulation effect and can effectively improve side effects such as immunosuppression caused by the antitumor drugs; and the carrier also has a pH sensitive response release characteristic, so that the targeting effect of the medicine in a tumor area is enhanced, and the innovative carrier has a good clinical application prospect.

The invention discloses an enantiokaurane compound with antitumor activity as well as a preparation method and application of the enantiokaurane compound. According to the present invention, chemical components of Western African plant I.trichantha tubers are deeply studied, and a variety of chromatographic separation methods such as macroporous resin, silica gel resin, medium pressure preparation-MCI column, gel normal pressure column and semi-preparative high performance liquid chromatography are combined to separate to obtain one enantiokaurane new compound Trichanthone B; experiments show that the compound obtained through separation has a good inhibition effect on an MIA PaCa-2 pancreatic cancer cell line and an A549 lung cancer cell line, and IC50 of the compound on the MIA PaCa-2 pancreatic cancer cell line reaches a nanomole level; the effect of the compound is stronger than that of positive drugs 5-fluorouracil and carboplatin, and the compound has the potential of being developed into new drugs for resisting pancreatic cancer and lung cancer.

The invention relates to the technical field of ferula asafoetida endophytic fungi separation and purification, in particular to alkaloid compounds in ferula asafoetida endophytic fungi as well as a preparation method and application of the alkaloid compounds in the ferula asafoetida endophytic fungi. And extracting with dichloromethane to obtain dichloromethane part extract, and purifying and separating the dichloromethane part extract by adopting silica gel column chromatography and high performance liquid chromatography to obtain the alkaloid compounds in the endophytic fungi of ferula sinkiangensis. The alkaloid compound in the ferula sinkiangensis endophytic fungi is disclosed for the first time, the compound is subjected to an in-vitro anti-tumor pharmacodynamic experiment, and according to the experiment result, the alkaloid compound has a certain inhibition effect on MCF-7 cells; therefore, the alkaloid compound can be used for preparing the medicine for preventing and treating the breast cancer, and a new medicine is provided for preventing and treating the breast cancer.

The invention relates to the technical field of medicines, and provides mitoxantrone-loaded ZIF-8 nanoparticles, a preparation method thereof and an application of the mitoxantrone-loaded ZIF-8 nanoparticles in tumor chemical-immunotherapy. Aiming at the defects of combined chemotherapy and immunotherapy clinically at the present stage, MIT ZIF-8 synthesized by a normal-temperature full-water-phase one-pot method is used as a novel chemical-immunotherapy scheme, and the capability of inducing cell immunogenic death of a chemotherapeutic drug mitoxantrone is enhanced by utilizing pyroptosis; the anti-tumor immune activation capability is enhanced while tumor cells are killed through chemotherapy, effective chemical-immune therapy is achieved, and the responsiveness of tumors to immune checkpoint inhibitor therapy is enhanced.

Drug delivery nanoparticle compositions and methods for the treatment of a cancer are provided that can be used individually or in combination. These compositions and methods include: (1) exogenous vaccination using neoantigens or tumor-associated antigens to potentiate an anti-tumor immune response; (2) nanoparticle-based drug delivery targeting the liver, aimed at reprogramming the hepatic immune environment to reduce or eliminate tumor antigen tolerance, thereby enhancing the immune system's ability to combat metastatic cancer; and (3) expansion of the liver metastasis treatment platform to target tumor-associated lymphoid structures, supporting the immune response at the primary tumor site. Any of these methods may be optionally combined with chemo-immunotherapy for enhanced efficacy.

The invention discloses an anti-tumor drug tablet stability prediction method based on multi-source data fusion, and particularly relates to the field of pharmaceutical preparation stability prediction, and the method comprises the following steps: S1, data acquisition; s2, extracting multi-dimensional characteristic parameters; s3, constructing a stability prediction reference model; s4, calculating a real-time attenuation index; s5, determining a deviation threshold range; s6, analyzing a stability deviation index; s7, dynamically updating a prediction result; according to the method, accurate prediction of content attenuation, related substance growth and disintegration time limit change indexes is realized through integration of multi-source data, construction of a stability prediction reference model, simple trend analysis not limited to a single factor, key influence factor marking, critical threshold setting and theoretical attenuation curve fitting; the accuracy and timeliness of stability prediction of antitumor drug tablets are effectively improved, and a scientific basis is provided for drug validity period evaluation and quality risk management and control.

The invention discloses a preparation method of polygonatum-sibiricum-sourced exosome-like nano-vesicles and application of the nano-vesicles in antitumor drugs, and relates to the technical field of biological medicines. The preparation method comprises the following steps: crushing fresh rhizoma polygonati slices, filtering and collecting to obtain a first filtrate; carrying out gradient centrifugation treatment on the first filtrate to obtain supernate; carrying out first membrane filtration treatment on the supernate to obtain second filtrate with the particle size of less than 450 nm; centrifuging the second filtrate to obtain a precipitate, and resuspending the precipitate with a PBS buffer solution to obtain a rhizoma polygonati exosome crude extract; and performing secondary membrane filtration treatment on the rhizoma polygonati exosome crude extract to obtain a third filtrate with the particle size of less than 220nm, thereby obtaining the rhizoma polygonati-derived exosome-like nano-vesicles. The polygonatum-sibiricum-sourced exosome-like nano-vesicle has remarkable inhibitory activity on tumors, provides a new strategy and means for tumor treatment, and has important scientific value and clinical application potential.

The embodiment of the invention provides breast cancer targeting nanoparticles as well as a preparation method and application thereof. According to the embodiment of the invention, the breast cancer targeting nanoparticles are synthesized by preparing the pH sensitive polymer, carrying out co-coupling modification on the pH response polymer and the folic acid albumin nano-carrier and utilizing a controlled desolvation method; the breast cancer targeting nanoparticle is combined with a nano preparation passive targeting strategy, a tumor microenvironment stimulation response strategy and a folic acid active targeting strategy, the effects of an EPR effect, PEG shedding, charge overturning, folic acid ligand-receptor combination and the like are utilized, precise targeting and specific response of tumors are achieved, and targeted accumulation of drugs in a tumor microenvironment is comprehensively improved. Therefore, the breast cancer targeting nanoparticles prepared by the embodiment have the advantages of high targeting property, drug controlled release, improvement of solubility and absorptivity of indissolvable drugs and the like, so that the curative effect of the drugs can be enhanced, the toxic and side effects can be reduced, and the breast cancer targeting nanoparticles have wide application prospects in the field of anti-tumor treatment.

The invention relates to the technical field of biological medicine, in particular to immunogen cell death enhanced nano-vesicle hydrogel and application thereof. The invention provides a 3D-printable multifunctional synergistic immunogen cell death enhanced nano-vesicle hydrogel, which is characterized in that SerMA hydrogel is used as a matrix, cell membrane nano-vesicles (N (at) ILO) loaded with a photothermal agent IR1061, a chemotherapeutic drug OXA and a tumor acidic microenvironment regulator Lon are encapsulated, initial tumor immunogen cell death is triggered through a photothermal effect, and the tumor immunogen cell death enhanced nano-vesicle hydrogel can be used for 3D printing. OXA further enhances the ICD effect, Lon regulates the acidic tumor microenvironment to improve the T cell activity, and postoperative multi-mode synergistic anti-tumor treatment is achieved; meanwhile, the hydrogel also has excellent photocuring 3D printing capability, can be used for individually constructing a filling structure matched with a postoperative defect area, has a wide application prospect, and provides a new strategy and theoretical basis for postoperative comprehensive treatment of choroidal melanoma.

The invention relates to the technical field of ferula asafetida endophytic fungus strain separation and purification, in particular to an alkaloid component in pleurotus nebrodensis as well as a preparation method and application thereof, and the alkaloid component in pleurotus nebrodensis, namely an alkaloid compound in pleurotus nebrodensis, is prepared by the following steps: crushing pleurotus nebrodensis sporocarp, adding methanol, heating, refluxing and extracting; dispersing the pleurotus nebrodensis total extract into a suspension with water, and extracting to obtain a petroleum ether part and ethyl acetate part extract; and carrying out gradient elution on the ethyl acetate part extract by silica gel column chromatography, and separating and purifying the third fraction by high performance liquid chromatography to obtain the alkaloid compounds in pleurotus nebrodensis. The invention discloses the alkaloid component in the pleurotus nebrodensis, namely the pleurotus nebrodensis alkali C for the first time, and the pleurotus nebrodensis alkali C has a certain inhibition effect on HGC-27 cells, so that the alkaloid component in the pleurotus nebrodensis, namely the pleurotus nebrodensis alkali C, can be applied to the preparation of tumor prevention drugs and antitumor drugs.

The invention discloses poplar and phellinus igniarius polysaccharide SVP-1 as well as a preparation method and application thereof, and belongs to the field of biological medicines. The poplar phellinus igniarius polysaccharide SVP-1 provided by the invention has remarkable anti-tumor activity, and can effectively inhibit proliferation, invasion and migration of tumor cells so as to block malignant progression of tumors. The structure is clear, the preparation method is controllable, the stability and biological activity of polysaccharide components are ensured, and a reliable basis is provided for development of antitumor drugs. When the traditional Chinese medicine composition is used together with radiotherapy and chemotherapy medicines, a synergistic effect can be achieved, the sensitivity of tumors to treatment can be improved, the toxic and side effects of radiotherapy and chemotherapy can be relieved, and the effects of reducing toxicity and increasing efficiency are achieved. According to the combined treatment strategy, the curative effect of the existing tumor therapy can be remarkably improved, meanwhile, adverse reactions are reduced, and a new optimization scheme is provided for clinical tumor treatment.

The present invention relates to a hetero (aromatic) ring-substituted cyclic diamine compound, the preparation thereof and the use thereof in the preparation of a drug for treating and / or preventing tumors. The structural formula of the compound is as shown in (I). The compound has a significant inhibitory effect on the growth of cells of tumors such as leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colorectal cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, nasopharyngeal carcinoma, liver cancer, gastric cancer and pancreatic cancer. Compared with the prior art, the compound of the present invention has a broad-spectrum anti-tumor activity, has a good effect on inhibiting tumors, and has an effect of degrading PD-L1 proteins, and is thus a PD-L1 immunomodulator.

The invention discloses a VEGF / TIE-2 dual-targeting polypeptide and application thereof in preparation of antitumor drugs, and relates to the technical field of biological medicines. The VEGF / TIE-2 dual-targeting polypeptide (named as RTP) provided by the invention is formed by combining an amino acid sequence capable of identifying VEGF and TIE-2 in a targeting manner, an amino acid sequence capable of forming beta-sheet nanofibers through self-assembly, an amino acid sequence capable of identifying carbonic anhydrase IX in a targeting manner and an enzyme reactive amino acid sequence capable of realizing MMP-2 specific shearing. The RTP can be subjected to allosteric and self-assembly in tumor cells to form stable water-insoluble nanofibers, the formation and metastasis of tumor neovascularization are strongly inhibited through VEGF and TIE-2 double signal channels, and the tumor progress is inhibited.

The present application relates to the technical field of small molecule drugs, in particular to a isoquinoline drug and its application in improving or treating digestive tract tumors, and aims to provide a compound, a pharmaceutical composition containing the compound and its application in treating colorectal cancer and gastric cancer, and provides a 3,13-position substituted berberine derivative, the drug itself has less toxicity and does not affect the growth of normal human cells, and has a good application prospect in the development of novel antitumor drugs, especially in the development of anti-digestive tract tumor drugs.

The invention discloses application of uncaria acidic polysaccharide URP-2 in preparation of an anti-esophageal cancer drug, and belongs to the technical field of antitumor of medicinal plant polysaccharide. According to the method, a method for extracting the uncaria total polysaccharide by boiling water and precipitating the uncaria total polysaccharide by ethanol is adopted, and a DEAE DE-52 cellulose column and sephadex column purification technology is combined, so that the separation of the uncaria acidic polysaccharide component is realized, and the uncaria acidic polysaccharide URP-2 is obtained. The uncaria acidic polysaccharide URP-2 comprises the following components in mole percent: 14.11% of arabinose, 12.64% of rhamnose, 6.48% of galactose, 5.00% of glucose and 61.77% of galacturonic acid. Experiments show that the uncaria acidic polysaccharide URP-2 has remarkable anti-esophageal cancer activity, so that a potential experimental basis and a new strategy are provided for applying the uncaria acidic polysaccharide URP-2 to clinical treatment of esophageal cancer.

The invention provides an alkaloid compound as well as a preparation method and an application thereof in tumor resistance. The alkaloid compound provided by the invention shows a remarkable cytotoxic effect on human non-small cell lung cancer cells A549, mouse lung adenocarcinoma cells Lewis, human triple negative breast cancer cells MDA-MB-231 and mouse breast cancer cells 4T1, and can be used for preparing medicines for treating breast cancer, lung cancer and the like.

The invention belongs to the technical field of medicines, and provides a novel method for overcoming multidrug resistance of tumors based on innate immune regulation. The invention relates to an application of an agonist of an innate immune STING pathway and an ENPP1 inhibitor in overcoming multidrug resistance of tumors and enhancing an anti-tumor curative effect. The STING agonist or the ENPP1 inhibitor is combined with an anti-tumor chemical drug for application, so that the effects of overcoming the multi-drug resistance of chemotherapeutic drugs and enhancing the anti-tumor curative effect are achieved. The STING agonist / or ENPP1 inhibitor has the effect of reversing multidrug resistance of tumors, and can enhance the sensitivity of cancer cells to chemotherapeutic drugs and monoclonal antibody drugs, so that the curative effect of antitumor drugs is enhanced, and the STING agonist / or ENPP1 inhibitor is expected to be developed into a novel reversal agent drug for multidrug resistance tumors. The novel anti-multidrug resistance strategy provides a new thought for drug design and cancer treatment, and has a great application prospect in clinical treatment of cancers.

The invention discloses a coumarin KRAS-G12C inhibitor as well as preparation and application of the coumarin KRAS-G12C inhibitor. The coumarin compound disclosed by the invention has a remarkable inhibition effect on non-small cell lung cancer cells (NCI-H23 and NCI-H358) with high expression of KRAS-G12C and pancreatic cancer cells (MIAPaCa-2), is particularly used for preparing medicines for treating and / or preventing non-small cell lung cancer and pancreatic cancer, and has a good prospect of development and application of antitumor medicines.

The invention discloses a naphthyridine mycin compound generated by streptomyces as well as a preparation method and application thereof, and belongs to the field of medicines. The naphthyridine mycin compound and the analogue of the naphthyridine mycin compound are prepared by fermenting, extracting, separating and purifying streptomyces lageri W307 (the preservation number of the strain is CGMCC (China General Microbiological Culture Collection Center) No.32721). The invention further discloses a preparation method of the naphthyridine mycin compound and the analogue of the naphthyridine mycin compound. The invention further provides application of the eight naphthyridine mycin compounds in preparation of anti-tumor drugs and application of the eight naphthyridine mycin compounds in preparation of antibacterial drugs, and potential anti-tumor drugs and antibacterial drugs are provided clinically.