949 results about "Antitumor activity" patented technology

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 a compound with anti-tumor activity. The compound has a chemical structural formula as shown in a formula (I). The compound belongs to a novel tetracyclic triterpenoid natural product, has good fat solubility and chemical stability, and can be conveniently extracted from the rhizome of a herbal medicine Polygala fallax Hemsl. And prepared into an oral or injection form. The invention also provides a preparation method and application of the compound. The compound provided by the invention can obviously inhibit the growth of mouse lung cancer and reduce the volume and weight of tumor, and can be used for treating tumor diseases.

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 relates to a turtle-derived cyclic peptide compound with an anti-tumor effect and a preparation method thereof. The preparation method comprises the following steps: crushing tortoise plastron, adding water for reflux extraction, filtering, concentrating and drying to obtain tortoise-shell glue; dissolving the obtained tortoise-shell gelatin in water, adding protease for enzymolysis, and centrifuging after enzyme deactivation to take supernate; carrying out graded filtration on the obtained supernate and collecting components; and separating and purifying the collected components to obtain the cyclic peptide. The obtained compound has remarkable anti-tumor activity and has a good application prospect in preparation of anti-tumor drugs.

The invention discloses an anti-tumor medicine composition combined with a PARG inhibitor and application. Through natural product library screening and CCK-8 experiments, it is found that PARG knockout gastric cancer cells show significantly enhanced sensitivity to ginsenoside CK. Further clone formation experimental analysis shows that PARG knockout significantly enhances the inhibitory effect of ginsenoside CK on gastric cancer cell proliferation. In in-vivo experiments, a CDX model is utilized to verify that PARG knockout can significantly enhance the anti-tumor activity of ginsenoside CK on gastric cancer. The discovery provides an important experimental basis for clinical application of PARG as a gastric cancer treatment target and ginsenoside CK as a potential treatment drug. The research finds that the PARG inhibitor and ginsenoside CK are combined to achieve a better killing effect on other various cancer cells, and it is indicated that improvement of the effect is broad-spectrum.

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 preparation method and application of roasted barley and malt polysaccharide with an anti-cancer effect. The roasted barley malt polysaccharide is a neutral heteropolysaccharide which mainly takes-> 3)-beta-D-Glcp-(1-> and->-beta-D-Glcp-(1->) as main chains, branches exist at O-3 / O-4 positions, and the branch chains are mainly composed of-> 4)-beta-D-Xylp-(1->,-> 3, 4)-beta-D-Xylp-(1-> and alpha-D-Glcp-(1->. The monosaccharide composition comprises arabinose, glucose and xylose in a molar mass ratio of 1.86: 33.43: 1.00, and the molecular weight is 23.81 kDa. In-vitro activity experiments prove that the roasted barley malt polysaccharide disclosed by the invention has a remarkable inhibition effect on proliferation of liver cancer cells, lung cancer cells, breast cancer cells and colorectal cancer cells, particularly on the liver cancer cells, and shows outstanding anti-tumor activity, so that the roasted barley malt polysaccharide is expected to be developed and applied in the fields of foods, health-care products or medicines.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a dammarane sapogenin-isatin derivative and application thereof in anti-tumor treatment. The dammarane sapogenin-isatin conjugate is constructed by taking dammarane sapogenin as a mother nucleus, deriving the dammarane sapogenin and chloroacetic acid and then introducing an indolone structural unit, and R1, R2 and R3 are as described in the claims and the specification. According to the invention, isatin fragments and ginsenoside are coupled for the first time, the anti-tumor activity of the compounds is systematically evaluated, and the action mechanism research of the compounds in colorectal cancer and other tumors is further developed. Results show that the obtained compound has relatively good anti-tumor efficacy, tumor cell selectivity, relatively low toxicity and relatively high bioavailability, and shows good patent medicine potential and wide market prospects.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The invention discloses an artemisinin derivative nano assembly with anti-tumor activity and a preparation method and application thereof. The nano assembly is formed by self-assembling artemisinin derivatives through intermolecular force and modifying the artemisinin derivatives with a PEG modifier; the artemisinin derivative is artesunate or dihydroartemisinin of which the side chain is binary acid or saturated fatty alcohol or unsaturated fatty alcohol; the mass ratio of the artemisinin derivative to the PEG modifier is (10: 90)-(90: 10), so that the technical effects of high drug loading capacity, good stability, low toxic and side effects and the like are realized, the urgent demand on high-efficiency and low-toxicity preparations in clinic is met, a new strategy is provided for the assembly of homotype synergistic drug nanoparticles, and the application prospect is broad. An effective nano platform is provided for developing a carrier-free nano assembly and a high-efficiency and low-toxicity nano preparation.

The invention relates to a hydroxamic acid derivative of benzimidazole as well as a preparation method and application of the hydroxamic acid derivative. Specifically disclosed are a compound represented by formula (I), a pharmaceutically acceptable salt thereof or a stereoisomer thereof. The hydroxamic acid derivative of benzimidazole is novel in structure, has good inhibitory activity on HDAC and / or PARP, and further shows good anti-tumor activity.

The invention discloses a benzoyl phenylurea selenium analogue, a preparation method and application thereof, and a pharmaceutical composition containing the benzoyl phenylurea selenium analogue, and belongs to the technical field of chemical synthesis and medicines. The benzoyl phenylurea selenium analogue has a remarkable inhibition effect on tubulin polymerization, has remarkable anti-tumor activity and has high application value in the cancer treatment process, raw materials for preparing the benzoyl phenylurea selenium analogue are easy to obtain, preparation conditions are mild, and the preparation method is simple and convenient.

The invention relates to an STING gene knockout TIL capable of enhancing anti-tumor activity and a preparation method and application of the TIL, in particular to a genetically engineered immune cell, and an STING gene in the genetically engineered immune cell is silenced or down-regulated. The ferroptosis resistance of the immune cell provided by the invention is remarkably enhanced, the immune cell can be better infiltrated into a tumor microenvironment, and the immune cell has a remarkable anti-tumor effect.

The invention discloses a carbamoyl-substituted diarylethene derivative as well as a preparation method and application thereof, and the preparation method comprises the following steps: reacting R-substituted 3-bromo-2-hydroxybenzaldehyde with an arylmethyl triphenylphosphonium bromide compound or an aryl acetic acid compound to obtain an intermediate A; then the intermediate A and cuprous cyanide are subjected to a heating reaction in N, N-dimethylformamide and nitrogen atmosphere, and an intermediate B is obtained; and finally, heating the intermediate B, acetaldoxime and indium trichloride in toluene for reaction to obtain the carbamoyl-substituted diarylethene derivative. The carbamoyl-substituted diarylethene derivative disclosed by the invention has a remarkable effect in an in-vitro anti-tumor activity test, particularly has excellent anti-proliferation ability to human BRCA mutant tumor cells, and can be used for preparing medicines for treating PARP-1 activity abnormity related diseases. The synthesis route is simple, the cost is low, and large-scale implementation is facilitated.

The present application relates to a kind of pH / H2O2 dual-response drug-loaded hydrogel and its preparation method and application, by ε-polylysine derivative as antitumor active ingredient, with oxidized dextran through Schiff base reaction crosslinking rapid gelation. While using 2-formylphenyl boronic acid covalently package CD73 small molecule inhibitor APCP. ε-polylysine derivative has oncolytic activity, can induce ICD and promote the infiltration of immune cells in tumor cells. CD73 small molecule inhibitor APCP can block extracellular CD39-CD73-adenosine pathway, reduce the level of immunosuppressive metabolite adenosine in tumor tissue, so as to activate the infiltrated immune cells, restore its anti-tumor function. The hydrogel of ε-polylysine derivative and APCP co-delivery synergistically inhibits the effect of tumor growth, and its curative effect is greater than the treatment effect of single drug, and is superior to positive control drug oxaliplatin (OXA). The pH / H2O2 dual-response hydrogel is rapidly gelled, and has good biological safety under mild reaction conditions.

Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor.

The invention relates to a hetero (aromatic) ring substituted cyclic diamine compound, preparation thereof and application of the hetero (aromatic) ring substituted cyclic diamine compound in preparation of drugs for treating and / or preventing tumors. The structural formula of the compound is shown as (I). The compound has an obvious growth inhibition effect on tumor cells of leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colorectal cancer, cervical cancer, lung cancer, prostate cancer, esophagus cancer, glioma, kidney cancer, nasopharynx cancer, liver cancer, stomach cancer, pancreatic cancer and the like. The compound disclosed by the invention has broad-spectrum anti-tumor activity; the compound has a good tumor inhibition effect and a PD-L1 protein degradation effect, and is a PD-L1 immunomodulator.

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

The invention relates to a lung cancer organoid and peripheral blood source immune cell co-culture model and a construction method thereof. Specifically, the invention provides a construction method of a macrophage and tumor organoid co-culture model for evaluating anti-tumor activity, monocytes of autologous or allogeneic peripheral blood of a patient are induced and differentiated into high-purity macrophages in vitro, and the high-purity macrophages and lung cancer tumor organoid are subjected to three-dimensional co-culture in matrigel; the model aims at highly reducing a core interaction network of tumor cells and macrophages in TME; the dynamic change of the polarization state of the macrophage is simulated and observed; the problem that an organ-like model is incomplete due to immune component deficiency or spatial positioning distortion of an existing model is effectively solved, an experimental platform closer to the physiological state is provided for tumor immune microenvironment research, and therefore development of the tumor immune treatment field is promoted.

The invention discloses a preparation method of anti-tumor hyaluronic acid-naringenin self-assembled nanoparticles, and belongs to the field of medicines. According to the method, carboxyl on hyaluronic acid and hydroxyl on naringenin are combined to form an ester group, and the hyaluronic acid-naringenin polymer is obtained. Hydrophilic hyaluronic acid is combined with hydrophobic naringenin to form a hydrophilic and hydrophobic polymer, then under the action of ultrasonic waves in an aqueous solution, the hydrophobic end repels water molecules and is mutually gathered, and the hydrophilic end wraps the periphery of the hydrophobic end and is in contact with water, so that the structure that the core is hydrophobic naringenin and the core is hydrophobic naringenin is formed. The outer core is a nanoparticle of hydrophilic hyaluronic acid. The particle size of the nanoparticles is 140-200nm, the nanoparticles are stable and uniform, in-vitro release experiment results show that the nanoparticles can be slowly released, and cell experiments show that the preparation can obviously improve the toxicity of naringenin to tumor cells, which shows that the nanoparticles have good anti-tumor activity.

The invention relates to application of a topoisomerase inhibitor and a conjugate thereof. Specifically, the inventor provides a class of camptothecin derivatives, linker conjugates and antibody-drug conjugates with novel structures, and the camptothecin derivatives, linker conjugates and antibody-drug conjugates have excellent anti-tumor activity and good lipophilicity. In-vitro and in-vivo experiments show that the drug conjugate containing the camptothecin derivative disclosed by the invention has an improved anti-tumor curative effect and high safety, and has an application prospect in the field of cancer treatment.

According to the AI-assisted marine microorganism anti-tumor activity product separation method provided by the invention, a microorganism strain with high anti-tumor activity potential can be directly and quickly screened out by constructing a marine microorganism sample database and applying a trained HetGNN model; the workload and time cost of tedious fermentation culture and biological activity testing in a traditional screening process are greatly reduced, meanwhile, the screening period is shortened, and the screening efficiency is greatly improved. Besides, a closed-loop feedback system formed by the invention feeds back a high-purity target compound sample separated from a laboratory and related data thereof to a microorganism sample database, and continuously optimizes the integrity of the database and the performance of the HetGNN model, so that the accuracy and efficiency of subsequent anti-tumor active compound screening are remarkably improved; the problem that in the prior art, screening precision is limited by initial data, and iterative upgrading is difficult is solved.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The invention provides a preparation method and application of a polyclonal antibody for recognizing IL-33 protein K6 site lactic acid modification, and belongs to the technical field of biological medicine, the invention discloses that lactic acid modification of IL-33 protein 6th lysine (Lys6) plays a key role in occurrence and development of liver cancer, and experiments prove that the site lactic acid promotes liver cancer cell proliferation and tumor growth; based on the discovery, the invention innovatively proposes that Lys6 lactic acid is used as a new target for tumor diagnosis and treatment, and successfully develops an antigen peptide and an antibody tool for specifically recognizing the modification site; the preclinical invention shows that the progress of the liver cancer can be effectively inhibited by blocking the Lys6 lactylation, the constructed detection system shows high sensitivity and specificity in liver cancer diagnosis, and the developed targeted antibody drug also has remarkable anti-tumor activity.

This invention belongs to the field of organic synthesis and relates to a nitrogen-containing [3,2-b]indole derivative, its preparation method, and its application. The nitrogen-containing [3,2-b]indole derivative is a compound, optical isomer, or pharmaceutically acceptable salt thereof, as shown in the following structure: ; wherein R1, R2, R3, and R4 are independently selected from hydrogen atoms, halogens, cyano groups, C1-C8 alkyl groups, and C1-C8 alkoxy groups; R5, R6, R7, and R8 are independently selected from hydrogen atoms, halogens, and C1-C8 alkyl groups; R9 is selected from C1-C8 alkyl groups; when R1, R2, R3, R4, R5, R6, R7, and R8 are all hydrogen atoms, R9 is selected from C1-C2 alkyl groups. The compound exhibits antitumor activity, particularly against HeLa cervical cancer, showing a significant inhibitory effect on its proliferation.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The application discloses a kind of based on fermentation of Sanghuangjun preparation's Radix Tetrastigae polysaccharide and its use.The Radix Tetrastigae polysaccharide is composed of polysaccharide with weight percentage content more than 99%;The polysaccharide is composed of galactose, mannose, fucose and 3-O-methyl-galactose, and the molar ratio is 8.5-11.0:1.5-3:0.8-1.5:1.0.The Radix Tetrastigae polysaccharide is extracted, separated and purified from Sanghuang fermentation Radix Tetrastigae.The Radix Tetrastigae polysaccharide has significant antitumor activity and regulates intestinal flora structure efficacy, can be directly used as antitumor and / or regulate intestinal flora structure function product, and also can be used for preparing antitumor and / or regulating intestinal flora structure function product.

The invention discloses a production process of a tumor swelling and pain relieving cataplasm patch, and belongs to the technical field of traditional Chinese medicine preparations. According to the process, rheum officinale, golden cypress, turmeric and tripterygium wilfordii stir-fried with vinegar are taken as monarch drugs and are matched with sculellaria barbata and oldenlandia diffusa to enhance the antitumor activity, pseudo-ginseng synergistically improves the transdermal efficiency, and the preparation is optimized through a segmented extraction and nano-targeting technology: 1) adopting supercritical COextraction to extract angelica dahurica and cinnamon volatile oil (20-25MPa and 40-50 DEG C), and carrying out beta-cyclodextrin inclusion; the preparation method comprises the following steps of (1) performing dynamic countercurrent extraction on non-volatile components (70% ethanol at a flow rate of 2.0 mL / min) of other medicinal materials, and coating triptolide (with a particle size of 80-150 nm) in combination with PLGA nanoparticles, and (3) mixing the extract and a composite matrix (sodium polyacrylate-sodium carboxymethyl cellulose-azone), and coating a pH response type chitosan-sodium alginate sustained release layer with the mixture to form the breathable patch.

The application discloses a kind of 2-substituted benzylhydrazine-4-indole pyrimidine-5-carbonitrile derivatives and preparation method and application thereof.The derivative has general formula (I) structure: wherein R is hydroxyl or C1-C4 alkoxy, n=1~3.Preferred compound is 2-hydroxy, 4-hydroxy-3-methoxy, 2,3-dihydroxy or 2,4-dihydroxy substituted benzylhydrazine derivative.The application also provides key intermediate 2-hydrazine-4-(1H-indole-3-carbonyl) pyrimidine-5-carbonitrile and preparation method thereof.In vitro antitumor activity shows that the derivative has excellent inhibitory activity on human gastric cancer cell MGC-803, and the inhibition rate is up to 96.3% at 10 μmol / L, which is better than positive control doxorubicin.In vivo combination test shows synergistic effect with 5-fluorouracil or anti-PD-1 antibody.The compound of the application has mild synthesis route, high yield, various preparation forms, good safety, and can be applied in the preparation of anti-gastric cancer drugs.

The invention belongs to the technical field of tumor treatment, and particularly relates to a metal polyphenol network coated drug-loaded mesoporous organic silicon nanoparticle and a preparation method and application thereof.The mesoporous organic silicon nanoparticle (MON) is prepared through a micelle / precursor co-template assembly method, then amination modification, carboxylation modification and drug co-loading are further conducted on the mesoporous organic silicon nanoparticle (MON), and the metal polyphenol network coated drug-loaded mesoporous organic silicon nanoparticle is obtained. The DQMCTH nano-particles are prepared through the steps that DQMCTH nano-particles are taken as a raw material, a copper salt solution and a tannic acid (TA) solution are added and mixed, then a coordination complexation reaction is conducted, hyaluronic acid (HA) is added for modification, and the DQMCTH nano-particles obtained through the method are in a sphere-like shape, regular in shape, uniform in distribution and free of obvious dendritic branches and central radial pore channels. The polypeptide is effectively protected by MPN and is subjected to HA targeted modification; more importantly, the DQMCTH nanoparticles prepared by the method disclosed by the invention show pH / GSH / HAase triple sensitive drug release, and cell and animal experiment results show that the DQMCTH nanoparticles prepared by the method disclosed by the invention have relatively high anti-tumor activity on a drug-resistant breast cancer model.