526 results about "Antitumor activity" patented technology

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 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.

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.

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 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.

The present invention relates to a novel antibody targeting B7-H3 or an antigen-binding fragment thereof, a chimeric antigen receptor (CAR) comprising same, an immune cell comprising the CAR, and uses thereof. The CAR-T cells according to the present invention have low toxicity and excellent antitumor activity, and thus can be effectively used in immune cell treatment for cancer treatment.

The application discloses a pyrrolobenzodiazepine-anthracene imide hybrid molecule and a preparation method and application thereof, and belongs to the technical field of chemical medicines. In order to solve the problems of few kinds of warheads of an existing antibody drug conjugate, single action mechanism and drug resistance easily generated in long-term use, a pyrrolobenzodiazepine-anthracene imide hybrid molecule shown in formula I and a preparation method and application thereof are provided. Experimental results show that the compound has strong anti-proliferation activity in various tumor cells such as ovarian cancer cells, gastric cancer cells and breast cancer cells, and an antibody drug conjugate thereof has good in-vivo and in-vitro anti-tumor activity and good safety.

The invention relates to the technical field of biological medicines, and discloses a blocking antibody targeting CXCL6 and an application of the blocking antibody in preparation of antitumor drugs. The antibody or antigen-binding fragment thereof is capable of binding specifically to human CXCL6 protein with high affinity (e.g., Kd < = 1 nM). According to the invention, the specificity and high affinity of the antibody are verified by Western Blot, immunofluorescence, immunohistochemistry and surface plasmon resonance (SPR) technologies. Functional experiments show that the antibody can effectively block CXCL6-induced neutrophil chemotaxis, including in Transwell, a three-dimensional gel model and a zebra fish living body model. Besides, in a mouse MC38 colon cancer model, the antibody shows remarkable anti-tumor activity and can inhibit tumor growth driven by CXCL6. The invention also provides a pharmaceutical composition containing the antibody, and application of the antibody in preparation of drugs for preventing or treating diseases (such as inflammatory diseases, autoimmune diseases and cancers) related to abnormal expression or activity of CXCL6.

The invention belongs to the technical field of microbial pharmacy, and discloses a polyketone macrolide compound generated by genetically engineered streptomyces as well as a preparation method and application thereof. The polyketone macrolide compound disclosed by the invention is a cinnamyl streptomycin derivative, has cell proliferation inhibition activity better than that of a natural product Cinnamomycin A-D, can exert anti-tumor activity by inhibiting activity of human exonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1) and activating an inherent immune pathway, can be prepared into a medicine or a medicinal composition, and can be used for preparing medicines or medicinal compositions. The compound is used for treating tumors and related diseases.

The application discloses an antibody targeting DLL3 and application thereof, and relates to the field of biological medicines. Specific anti-DLL3 nanobodies are screened in the embodiment of the application, and a bispecific antibody constructed from the anti-human DLL3 nanobody or humanized nanobody and an anti-human CD3 antibody is prepared, the obtained bispecific antibody has good antitumor activity, can be applied to preparation of at least one drug for preventing or treating a DLL3 expression abnormality related tumor or cancer disease including small cell lung cancer, and has wide application.

The present disclosure provides a nanobody platform having a high affinity purification on protein A, wherein the nanobodies may incorporate diverse bioactive peptides, lipid or glycoside in its CDR1 and / or CDR3 regions. The present disclosure also provides a peptide-modified nanobody comprising non-toxic bioactive peptides and that exhibit potent anti-tumor activity. Moreover, the peptide-modified nanobody is able to be combined with other technologies, such as but not limited to bispecific antibodies and antibody-drug conjugates. Further, the present disclosure also provides production processes of the nanobodies and their use as a treatment and diagnostic agents.

This invention discloses the application of Uncaria rhynchophylla neutral polysaccharide URP-W in the preparation of anti-glioma drugs, belonging to the field of anti-tumor technology of medicinal plant polysaccharides. The invention obtains a crude polysaccharide extract from Uncaria rhynchophylla through hot water extraction and ethanol precipitation, followed by purification using a DEAE cellulose column and G200 dextran gel to obtain Uncaria rhynchophylla neutral polysaccharide URP-W. The monosaccharide composition of URP-W includes arabinose, rhamnose, galactose, glucose, xylose, mannose, galacturonic acid, and mannuronic acid in a molar ratio of 17.99:6.32:21.71:27.17:2.56:7.57:16.20:0.49. Experiments have shown that URP-W can inhibit the proliferation of gliomas and induce apoptosis, exhibiting significant anti-tumor activity against glioma cells, providing a new drug raw material and treatment method for the clinical treatment of gliomas.

This invention discloses an enhanced CAR-T cell (CARTAC) capable of secreting a targeted membrane protein degrader and its applications. While retaining specific killing function, this cell can expand locally in tumors and continuously secrete the bispecific adaptor molecule scTAC. scTAC can recruit E3 ubiquitin ligases, mediate ubiquitination of tumor cell surface membrane proteins (such as PD-L1), and achieve targeted degradation via the lysosomal pathway, effectively reversing the immunosuppressive microenvironment, overcoming antigen heterogeneity, and eliminating antigen-negative tumor cells through the bystander effect. This invention also utilizes the efficient endocytosis properties of EGFR to design scTAC-dual, which can further enhance degradation efficiency. In various lung cancer mouse models, CARTAC-dual exhibited excellent tumor infiltration capacity, low exhaustion levels, and sustained antitumor activity, without systemic toxicity. This invention integrates the targeted killing and protein degradation delivery functions of CAR-T cells, not only enhancing the control effect on solid tumors but also possessing target scalability, making it suitable for the universal upgrading of various CAR-T products.

The present disclosure provides methods of treating cancer in a patient determined to have an HER2 exon 21 mutation by administering a third-generation tyrosine kinase inhibitor, such as poziotinib.

The application belongs to the technical field of medicine, and relates to N-methyl-2-(9-oxoacridin-10(9H)-yl)acetamide compounds and a preparation method and application thereof. The preparation method of the compound is as follows: taking o-aminobenzoic acid as a starting material, performing substitution reaction, condensation reaction, alkylation reaction and hydrolysis reaction to generate a key intermediate acridone acetic acid, and finally performing condensation reaction on the acridone acetic acid and substituted pyrimidine in the presence of TCFH and NMI condensing agents to obtain the target compound. The preparation method of the N-methyl-2-(9-oxoacridin-10(9H)-yl)acetamide compound provided in the application is simple and feasible, and good results are shown in in-vitro anti-tumor activity tests, and the compound has excellent anti-proliferation ability on human breast cancer cells BT-549 and MDA-MB-231 in particular.

The application provides a combination drug of a PLA2G7 inhibitor and a chemotherapeutic drug and its use in resisting triple-negative breast cancer, and belongs to the technical field of medicines. The combination drug is a PLA2G7 inhibitor and a chemotherapeutic drug in the same or different specifications of unit preparations for simultaneous or separate administration, and a pharmaceutically acceptable carrier. The application first discovers and proves that the PLA2G7 inhibitor Darapladib can significantly enhance the anti-tumor activity of paclitaxel, 5-fluorouracil or cisplatin on triple-negative breast cancer, and meanwhile, the combination of the PLA2G7 inhibitor and paclitaxel has a synergistic effect in down-regulating the phosphorylation level of STAT3 protein in cancer cells and inhibiting the growth and proliferation of cancer cells; the combination of the PLA2G7 inhibitor and 5-fluorouracil also shows a synergistic effect in inhibiting the growth and proliferation of cancer cells. The application provides a new and effective combination drug strategy for improving the treatment effect of the chemotherapeutic drug on triple-negative breast cancer.

This application belongs to the field of biomedicine, specifically relating to a method for preparing an antitumor composition for pets, aiming to solve the technical problems of low bioavailability, poor stability, and poor drug administration compliance of poorly soluble active ingredients in antitumor drugs for pets. The method includes: a raw material pretreatment step, in which curcumin, resveratrol, quercetin, green tea polyphenols, and astragalus polysaccharides are pulverized and sieved separately; an organic phase preparation step, in which egg yolk lecithin and solid lipids are dissolved in an ethanol-acetone mixed solvent, and curcumin and resveratrol are added and dissolved by stirring in a water bath; an aqueous phase preparation step, in which poloxamer F68 is dissolved in purified water and dissolved in a water bath; a high-pressure homogenization step, in which a nanoemulsion containing a solid lipid core is prepared; a moderately polar component encapsulation step, in which quercetin and green tea polyphenols are ultrasonically dispersed and then added dropwise to the nanoemulsion; a freeze-drying step, in which a nano-lyophilized powder is obtained; and an outer hydrophilic component coating step, in which astragalus polysaccharides are sprayed or adsorbed onto the surface of the freeze-dried powder. The composition obtained by this method is a core-shell multilayer nanoparticle with a core consisting of curcumin and resveratrol encapsulated by solid lipids, a middle shell adsorbing quercetin and green tea polyphenols, and an outer shell coated with astragalus polysaccharides. This application utilizes the above-mentioned layered encapsulation technology to achieve stable co-encapsulation of multiple antitumor active ingredients, improve the bioavailability of poorly soluble components, optimize drug stability, and enhance antitumor effects through multi-target synergistic effects. Simultaneously, it endows the composition with immunomodulatory functions and sustained-release properties. The composition can be formulated into a nano-lyophilized powder form, making it easy to add to pet food or formulate into a paste for administration, improving pet drug compliance. Figure 2 is a schematic diagram of the three-layer core-shell nanoparticle structure of the composition of this invention.

Provided herein are novel αPD-L1 antibodies and methods of using such antibodies for the treatment of cancers. In some embodiments, the antibodies are αPD-L1×αCD28 bispecific antibodies. Such antibodies enhance anti-tumor activity by providing a costimulatory signal for T-cell activation against tumor cells while advantageously also blocking inhibitory PD-L1:PD-1 pathway interactions.

This invention discloses a polysubstituted indole[1,2-a]quinoxaline compound, its preparation method, and its applications. The structural formula of the polysubstituted indole[1,2-a]quinoxaline compound of this invention is or , where R 1 Selected from -H or -F, R 2 The compounds are selected from phenyl, 4-methylphenyl, 4-methoxyphenyl, or 4-fluorophenyl. The polysubstituted indole[1,2-a]quinoxaline compounds of this invention have novel structures and significant antitumor activity, making them suitable for the synthesis of anticancer drugs. Furthermore, their preparation methods offer advantages such as readily available and inexpensive catalysts, broad substrate applicability, good functional group tolerance, simple operation, mild reaction conditions, and high step economy, making them suitable for large-scale industrial production and application.

This invention discloses antibodies against ROR1 or their antigen-binding fragments, kits, and their applications, relating to the fields of biotechnology and medical technology. This invention screened and obtained 10 antibodies that have high affinity for the ROR1 protein and can specifically bind to it. This allows for the development of ROR1 detection kits, tumor diagnostic and prognostic kits, as well as pharmaceutical compositions, antibody-drug conjugates, or other therapeutic methods using the aforementioned antibodies or their antigen-binding fragments. Experimental verification shows that the antibodies provided by this invention have a high killing rate against tumor cells. All of the above antibodies exhibit concentration-dependent cytotoxicity; the higher the antibody concentration, the better the anti-tumor activity. Therefore, the antibodies or their antigen-binding fragments provided by this invention show promising potential for the preparation of tumor therapeutic drugs.

Disclosed are an anthracycline compound, a preparation method therefor, an intermediate, and a use thereof. The present invention provides an anthracycline compound as shown in formula I or a pharmaceutically acceptable salt thereof. The anthracycline compound provided by the present invention has antitumor activity comparable to existing anthracycline drugs (such as nemorubicin) or greater than that of existing anthracycline drugs doxorubicin and daunorubicin, and does not form an oxazole ring structure during metabolism, thereby improving the clinical safety of such drugs.

The invention provides an anti-FOLR1 nano antibody and related application thereof, and relates to the technical field of biological medicines. The nano antibody can be combined with an FOLR1 antigen with high affinity and specificity. An in-vitro experiment verifies that the FOLR1-CD3 bispecific antibody constructed on the basis of the FOLR1-CD3 bispecific antibody shows remarkable killing activity on various FOLR1 positive tumor cells, can be used for treating cancers and other diseases related to FOLR1 expression, and provides an important basis for developing an immunotherapy strategy with efficient and lasting anti-tumor activity.

The application discloses a tetravalent platinum ester alkyne complex, a degradable high polymer, a nanomicelle and a preparation method and application thereof; the structural formula of the tetravalent platinum ester alkyne complex is shown as formula (I); the preparation method of the degradable high polymer is as follows: the tetravalent platinum ester alkyne complex is prepared first; then the obtained tetravalent platinum ester alkyne complex and diamine and monomethyl ether polyethylene glycol mPEG-NH2 are clicked to obtain a triblock high polymer. The nanomicelle of the degradable high polymer is also disclosed. The tetravalent platinum ester alkyne complex disclosed by the application can specifically respond to reducing substances in a tumor microenvironment, and the enamine ester structure generated by the reaction of the tetravalent platinum ester alkyne complex with diamine also has the property of responding to an acidic environment; the high polymer has mild and simple preparation conditions, the molecular weight can reach 35200, and the platinum drug loading capacity is as high as 33.91%; the nanomicelle can efficiently degrade and release anticancer active drugs in the tumor microenvironment, and has high antitumor activity and low cytotoxicity.

The disclosure belongs to the technical field of medicine. Provided are a CD97 and GSDME interaction inhibitor having anti-tumor activity and an application thereof. A compound screened in the disclosure enhances the susceptibility of NK cells to kill tumor cells by inhibiting the interaction between GSDME and CD97 in tumor cells, so as to induce an immune anti-tumor effect. Moreover, the compound enhances the susceptibility of tumor cells to pyroptosis by blocking the protective effect of CD97 on cleavage of GSDME proteins. Therefore, the compound can be used for treating GSDME and CD97 double-positive malignant tumors, and combined chemotherapy, immunotherapy, etc., to enhance the susceptibility of malignant tumors to chemotherapy and immunotherapy, prolonging the overall survival period of patients with malignant tumors. Specifically provided is a compound having a structure set forth in formula (I), a pharmaceutically acceptable salt, a solvent compound or a deuterated compound thereof.

According to the synthetic method of the indole derivative and the application of the indole derivative in preparation of the medicine for resisting children nephroblastoma, coupling reaction of aniline compounds and alpha-oxocarboxylic acid is achieved through an electro-organic synthesis strategy, efficient preparation of the three polysubstituted indole derivatives is achieved, the reaction conditions are mild, the yield is high, and the method is suitable for industrial production. And the method is simple and convenient to operate, does not need to use a toxic strong oxidant, and has good synthesis applicability and environmental friendliness. Experimental results show that the synthesized polysubstituted indole derivative shows remarkable anti-tumor activity on children nephroblastoma cell lines, can obviously inhibit tumor cell proliferation, and has the potential of being further developed into anti-nephroblastoma drugs.

The invention relates to the technical field of medicines, and discloses a bifidobacterium longum strain GZBAI 01 and application thereof in degradation of benzoic acid and prevention or treatment of colorectal cancer. The strain is separated from faeces of healthy people, genomics identification is carried out, the metabolic profile of the strain is measured through metabonomics, the strain can convert benzoic acid with carcinogenic risk into protocatechuic acid with antitumor activity through unique metabolic capability, meanwhile, the function of regulatory T cells (Treg) in tumor drainage lymph nodes can be inhibited, differentiation of CD8 + T cells is promoted, and the tumor drainage lymph nodes can be inhibited. Therefore, the colorectal cancer is prevented through double ways of eliminating cancerogen and generating therapeutic agents. A colorectal cancer mouse model and a subcutaneous tumor mouse model verify that the strain can significantly reduce the number and volume of tumors, and shows a benzoic acid conversion effect superior to that of other strains in vivo and in vitro, and a new way is provided for prevention and treatment of colorectal cancer.

The present application provides a method for preparing nitrogen-containing fused ring compounds with antitumor activity, which can efficiently obtain the target product under relatively mild reaction conditions, and compared with the original process, the yield is significantly improved and the material cost is significantly reduced, which facilitates the scale-up of the process.

The invention discloses an MEK / HDAC double-target inhibitor as well as a synthesis method and application thereof, and belongs to the technical field of medicines. Through molecular docking and in-vitro thermodynamic migration experiments, the applicant finds that the inhibitor not only can stabilize MEK and HDAC proteins, but also can be specifically combined with the MEK and HDAC proteins in an intracellular environment; protein immunoblotting experiments find that the inhibitor can inhibit reactivation of ERK, overcomes the limitation of a single-target inhibitor in curative effect and activity, and significantly improves the drug resistance problem of trametinib in ovarian cancer treatment and various EGFR-TKI treatment in non-small cell lung cancer treatment; furthermore, an in-vitro anti-tumor activity experiment shows that the IC50 value of the MEK / HDAC inhibitor on tumor cells from human ovarian cancer and various lung cancers is 0.07-10 mu M, and the MEK / HDAC inhibitor has a wide and remarkable proliferation inhibition effect.