131 results about "Drug target" patented technology

This invention discloses an AfBPP-based active molecular probe for thiostreptin, its preparation, and its application, belonging to the field of chemical biology. This invention introduces a bifunctional tag integrating a photocrosslinking group (bisacrididine) and a bioorthogonal reactive group (alkynyl group) into the structure of thiostreptin. While retaining the original biological activity of the parent compound, it endows the probe with highly efficient probe function, solving the technical problem of target loss during washing and purification of traditional non-covalent probes. After target labeling, the probe can specifically connect to reporter groups such as fluorescein or biotin through click-chemical reactions, achieving efficient enrichment of drug targets. Combined with mass spectrometry analysis, it enables global identification of potential targets in cells or complex biological samples at the omics level, such as chemical proteomics, providing a powerful molecular tool for in-depth revelation of the potential targets and pharmacological mechanisms of thiostreptin.

This invention provides a data storage method and system for tuberculosis detection, relating to the field of tuberculosis detection technology. The data storage method for tuberculosis detection includes the following steps: S1. Collecting whole-genome sequencing data of Mycobacterium tuberculosis, host serum IgG titer, and drug sensitivity test results; S2. Calculating genetic distance D based on a reverse evolution model to generate four-dimensional spatiotemporal coordinates (t, x, y); S3. Performing data partitioning and storage based on the drug target barrier value β; S4. Generating dynamic metadata using a host-pathogen dynamics model and compressing and storing it. This invention implements a dynamic storage entropy adjustment algorithm at the hardware and software collaborative level, continuously optimizing the matching efficiency of data compression and physical storage. This results in an intelligent data hub that can perceive the evolutionary pulse of pathogens and autonomously optimize resources, providing support for clinical tuberculosis prevention and control decisions with temporal depth, spatial correlation, and risk evolution.

This invention discloses compounds of Formula I, or pharmaceutically acceptable salts, isomers, racemates, precursors, or solvates thereof. Compounds of Formula I exhibit excellent inhibitory activity against RSK protein kinase, thus showing promise for development into drugs targeting RSK.

The present application relates to the field of biological medicine and modernization of traditional Chinese medicine, and particularly relates to a therapeutic target, an inhibitor and a traditional Chinese medicine composition for treating ovarian hypofunction caused by oxidative stress and application thereof. The present application first determines SRC tyrosine kinase as a key drug target for preventing and treating the disease. The application of the SRC tyrosine kinase inhibitor (such as secaitinib) in preparing related drugs is provided, which can alleviate the damage of ovarian granulosa cells by inhibiting the SRC activity, down-regulating the expression of antioxidant enzyme related genes and reducing the level of active oxygen. Meanwhile, the present application provides a traditional Chinese medicine composition composed of mulberry, kudzu root, tuckahoe and medlar. The composition can improve the hormone level, enhance the antioxidant capacity, improve the ovarian function and fertility by inhibiting the SRC tyrosine kinase activity and the SRC-RAF1-MEK-ERK signal pathway. The present application provides a new solution for the targeted treatment of ovarian hypofunction and the modernization of traditional Chinese medicine.

This invention discloses the application of ESCO1 and NUFIP2 in the diagnosis and treatment of pancreatic cancer, relating to the field of biomedical technology. This invention provides the application of ESCO1 and / or NUFIP2 as pancreatic cancer biomarkers in the preparation of pancreatic cancer diagnostic or prognostic assessment products, and also provides the application of ESCO1 and / or NUFIP2 as drug targets in the screening or preparation of drugs for the prevention and / or treatment of pancreatic cancer. This invention discovers that ESCO1 and NUFIP2 have important biological significance in pancreatic cancer, with NUFIP2 expression regulated by ESCO1, and both expression levels positively correlated with the malignant progression of pancreatic cancer. Therefore, ESCO1 and NUFIP2 can not only serve as potential diagnostic biomarkers and therapeutic targets for pancreatic cancer, but also provide new theoretical basis and research directions for optimizing pancreatic cancer immunotherapy strategies.

This invention provides a high-throughput method for constructing dual sgRNA libraries and its applications. The method utilizes high-throughput microarray synthesis technology to prepare a set of DNA fragments containing multiple dual sgRNA expression cassettes in a single step. After amplification, these fragments are assembled with a target vector containing a first promoter and a second gRNA backbone sequence in a first round of directed assembly to obtain a preliminary recombinant plasmid set. Then, linearized enzyme digestion and homologous recombination technology are used to insert a fragment containing a transcription termination sequence and a complete second promoter to complete the construction of the dual sgRNA expression unit. Finally, transformation and amplification yield the dual sgRNA plasmid library. This invention avoids the high error rate and high cost of long-chain oligonucleotide synthesis by utilizing microarray synthesis and simplifies the operation process through two rounds of directed assembly, significantly improving the throughput, fidelity, and efficiency of library construction. It is applicable to the construction of genome-wide dual sgRNA libraries, providing an efficient and reliable technical platform for high-throughput gene function screening, drug target discovery, and gene interaction research based on CRISPR.

The present application relates to the field of biotechnology, in particular to a kit based on functionalized magnetic beads and application thereof in the field of stem cells. The functionalized magnetic beads of the present application are loaded with extracellular matrix proteins on the surface, and the extracellular matrix proteins are selected from collagen. The functionalized magnetic beads of the present application realize efficient capture and enrichment of collagen-bound transmembrane proteins, combined with mass spectrometry identification, and are suitable for screening stem cell transmembrane proteins, studying the action sites of stem cells and matrix, or developing drugs targeting stem cells. The kit and method of the present application have the technical advantages of simple operation, good stability and strong specificity, and provide a powerful tool for systematic study of the cell-matrix interaction mechanism mediated by stem cell transmembrane proteins.

This invention belongs to the field of biomedicine, and relates to single-domain antibodies, more specifically to a humanized single-domain antibody targeting VEGF and its applications. The amino acid sequence of the single-domain antibody includes three complementarity-determining regions (CDR1-CDR3) and four backbone regions (FR1-FR4). This invention also provides a recombinant protein containing the single-domain antibody, a nucleic acid molecule encoding the single-domain antibody or recombinant protein, a vector containing the nucleic acid molecule, a host cell containing the nucleic acid molecule or vector, and the application of the single-domain antibody or recombinant protein in the preparation of drugs targeting VEGF to treat diseases.

This invention belongs to the medical field and provides a human trophoblastic stem cell line derived from complete hydatidiform mole and its applications. The human trophoblastic stem cell line, with accession number CGMCC No. C2024411, can be induced to differentiate into syncytiotrophoblast and extravillous trophoblast, mimicking the differentiation and developmental defects of the trophoblastic lineage in hydatidiform mole. It can be used as an in vitro research model for complete hydatidiform mole and has broad application prospects in drug target research and genetic studies.

This invention discloses a biomarker for vasovagal syncope, its extraction method, and its application, relating to the fields of medicine and immunology. The biomarker for vasovagal syncope described in this invention is circulating small extracellular vesicle miRNAs. This invention also discloses the application of the biomarker for vasovagal syncope as a drug target in the preparation of drugs for the prevention and / or treatment of vasovagal syncope. This invention further discloses a drug / drug composition. The biomarker for vasovagal syncope described in this invention provides new directions and ideas for the screening, diagnosis, and therapeutic targets of vasovagal syncope. This invention has broad application prospects.

This invention discloses the application of a branched-chain amino acid (BCAA) restricted diet in the preparation of drugs for treating liver metastases of tumors. Through mouse model experiments, this invention found that restricting the intake of BCAAs (valine, isoleucine, and leucine) in the diet, or using the SCD1 inhibitor A939572, can significantly inhibit liver metastases of tumors, especially pancreatic cancer liver metastases. Experimental results show that a BCAA restricted diet or SCD1 inhibitor can reduce the number and volume of liver metastases and inhibit their growth. This invention also reveals its mechanism of action: BCAA restriction reduces the propionylation modification of SREBP1, downregulates the transcriptional expression of its target gene SCD1, and thus reduces lipid synthesis, thereby exerting an anti-tumor liver metastasis effect. This invention provides a novel dietary intervention strategy and drug target for the treatment of liver metastases of tumors.

This invention discloses compounds of Formula I or pharmaceutically acceptable salts thereof. Compounds of Formula I exhibit excellent S1PR1 receptor modulatory activity and high selectivity, thereby effectively avoiding potential cardiovascular toxicity while exerting immunomodulatory effects. The compounds and pharmaceutical compositions of this invention lay a solid chemical and biological foundation for the development of next-generation drugs targeting autoimmune diseases and specific malignant tumors, demonstrating promising clinical application prospects, social benefits, and potential industrialization value.

The application provides application of nucleolin as a drug target in preparation of a double-targeted treatment drug for colorectal cancer, and application of nucleolin as a double-targeted drug target in preparation of a drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, the drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, a pharmaceutical composition containing the drug and application thereof. The application uses nucleolin as a common drug target of colorectal cancer tumor cells and tumor-related fibroblasts, applies a double-targeted killing drug with nucleolin as a target, simultaneously kills colorectal cancer tumor cells and tumor-related fibroblasts, removes tumor cells while destroying tumor-related fibroblast-mediated tumor supporting microenvironment, and synergistically enhances the overall treatment effect of colorectal cancer.

This invention provides the application of the IFI16 gene as a target in the preparation of bortezomib-resistant drugs for the treatment of multiple myeloma, involving drug targets, related diagnostic reagents, and treatment strategies for the diagnosis and treatment of multiple myeloma (MM). This invention reveals for the first time the core driving role of IFI16 in bortezomib resistance in MM and its novel mechanism of action through the Wnt / β-catenin pathway; more importantly, it provides novel biomarkers, drug targets, and highly feasible combination therapy regimens for accurate prognostic assessment of MM and overcoming the clinically challenging problem of bortezomib resistance, possessing significant theoretical implications and broad clinical application prospects.

This invention discloses a drug target affinity prediction method that integrates PPI quality and uncertainty. The method constructs a drug molecule map and a multimodal protein structure representation, and extracts multi-source features by combining the local PPI sub-map of the target protein. By calculating the protein's low-frequency level, prediction uncertainty, and PPI quality, a PPI quality-aware gating factor is generated to adaptively adjust the PPI information injection intensity, and a residual enhancement strategy is used to preserve the original protein features. Subsequently, the drug representation and the enhanced protein representation are fused using adaptive gating, and the result is input into a prediction network to output the drug-target affinity. This method effectively integrates protein function and interaction information, improves the prediction stability of low-frequency proteins and the model's generalization ability, and provides an accurate and reliable computational tool for drug screening and candidate molecule selection.

This invention belongs to the field of biomedicine and discloses estradiol derivatives or pharmaceutically acceptable salts thereof with the structure shown in Formula I: R is selected from R1, which is selected from F, Cl, Br, and I; L is selected from straight-chain or branched alkyl groups with 2 to 10 carbon atoms. This invention also discloses the use of the estradiol derivatives or pharmaceutically acceptable salts thereof in the preparation of drugs for treating depression and anxiety. Furthermore, this invention discloses the use of the estradiol derivatives or pharmaceutically acceptable salts thereof in the preparation of drugs targeting ERβ / SERT for treating depression and anxiety. The estradiol derivatives of this invention can simultaneously and effectively inhibit SERT and activate ERβ, thereby synergistically enhancing serotonergic neurotransmission and regulating neuroplasticity, and enhancing antidepressant efficacy through multi-target synergistic effects.

This invention discloses a drug-target interaction prediction method based on graph neural networks, belonging to the field of bioinformatics. It addresses the problem of inaccurate interaction prediction by acquiring molecular structure data of the target drug and target data of the target target; constructing a molecular neural network graph of the target drug and a target neural network graph of the target target, obtaining atomic node vectors, atomic edge vectors, target node vectors, and target edge vectors; constructing molecular feature vectors of the target drug and target feature vectors of the target target, thereby obtaining a drug-target interaction prediction matrix; setting positive and negative samples and training using a multilayer perceptron network model to obtain a drug-target interaction prediction model; and using the drug-target interaction prediction model to identify the target drug and target target, determining the interaction between them. This invention achieves accurate prediction of the interaction between the target drug and target target.

A determination has been made that apicomplexan tubulin, an essential parasite component, is an excellent drug target. Here, it is shown that it is possible to specifically target parasite tubulins, without harming the mammalian host. A compound has been identified that destabilizes specifically parasite MTs and inhibits essential parasite processes of replication and host cell invasion. This provides a new strategy to tackle the issue of drug resistance development. Specifically, the use of the compound parabulin and / or its derivates in the process of targeting protozoan tubulin for the inhibition of the replication of protozoans in mammalian organism, wherein parabulin has the following molecular weight, sum formula, name and structure:MW: 373.4 Da;Formula: C20H23NO6, ⋅Name (s): 3-(3,4-dimethoxyphenyl)-N-[(3,4,5-trimethoxyphenyl)methyl]prop-2-enamide; (2E)-3-(3,4-Dimethoxyphenyl)-N-(3,4,5-trimethoxyphenyl)acrylamid;SMILES:0(C1═C(OC)C═CC(═C1)C═CC(═0)N(CC2═CC(═C(OC)C(═C2)OC)OC)[H])C.

This invention belongs to the field of biomedicine, specifically relating to small interfering RNA (sRNA) targeting the TNF-α gene; it includes a sense strand and an antisense strand; the sense strand and / or the antisense strand has a length ranging from 19 to 25 nucleotides, and the antisense strand is inversely complementary to a segment on the target gene. Furthermore, it achieves drug delivery of the small interfering RNA through a specific target gene, enabling precise drug targeting at the site of colonic inflammation, enhancing the therapeutic effect of IBD without causing systemic immunosuppression, thus providing a more precise and efficient gene regulation tool.

The application discloses application of an SNRPF-DDX24-E2F4 loop in preparation of an ovarian cancer drug or an ovarian cancer prognosis evaluation product, and belongs to the field of biomedical technologies.The SNRPF-DDX24-E2F4 loop is used as a drug target for preparing a drug for treating ovarian cancer and / or as a biomarker for preparing a product for evaluating the prognosis of ovarian cancer; wherein the SNRPF-DDX24-E2F4 loop refers to a self-reinforcing positive feedback regulation loop composed of SNRPF, DDX24 and E2F4; SNRPF maintains the expression of a DDX24 protein coding type transcript by regulating the correct splicing of intron 6 of the DDX24 gene; DDX24 maintains the expression of an E2F4 protein coding type transcript by regulating the correct splicing of intron 2 of the E2F4 gene; E2F4 directly combines with the SNRPF promoter and activates the transcription thereof as a transcription factor, thereby forming a closed positive feedback regulation loop; the application discloses the existence of the loop in ovarian cancer and the core driving effect thereof, provides a new target and a new application for preparing an ovarian cancer drug, provides a new biomarker and a detection method for evaluating the prognosis of ovarian cancer, and has important clinical transformation value and a wide application prospect.

The application discloses a drug-target binding affinity prediction model training method and a prediction method based on contrast learning, and belongs to the technical field of drug-target binding affinity prediction. In order to solve the problem that the prediction effect of the existing DTA prediction based on contrast learning needs to be improved, the application selects positive and negative samples according to the similarity between drug molecular structures, the similarity between target sequences, and the similarity between drugs and targets in an affinity graph to optimize the effect of contrast learning, extracts drug-target features of three different scales of sequences, molecular structures and affinity graphs, fully utilizes drug and target information, captures potential relationships between cross-scale feature information through a multi-scale feature contrast learning framework, maximizes mutual information between different scales, and performs feature alignment and feature fusion, and then obtains a prediction model based on contrast loss, and the prediction model is used to realize drug-target binding affinity prediction.

This invention belongs to the field of biomedicine, specifically relating to the development and application of oligonucleotide drugs targeting the key assembly proteins G3BP1 / 2 of stress granules. The oligonucleotides in these drugs are all composed of 20 bases, with 5 bases at each end modified with 2'-O-methoxyethyl, and 10 consecutive ordinary bases in the middle to ensure targeting specificity. Simultaneously, the entire nucleic acid chain is modified with thiophosphorylation. The oligonucleotide molecules disclosed in this invention possess targeting specificity, high molecular activity, and in vivo metabolic stability, providing research directions and candidate drugs for clinical targeting of stress granules and improvement of neurodegenerative diseases such as ALS.

This invention proposes a drug target interaction prediction method based on graph interaction and multi-granularity fusion, belonging to the field of bioinformatics. Addressing issues such as oversmoothing of graph neural networks in heterogeneous graphs, insufficient utilization of drug-target interactions and multi-scale information, and poor adaptability of multi-branch feature splicing, an improved method is proposed. First, a deep interactive graph neural network branch is constructed on the node adaptive local smoothing features and the heterogeneous graph composed of drug-drug, target-target, and drug-target edges, realizing message passing and fusion of classification edges and introducing residual connections. Second, a dual-tower interactive branch is constructed for multi-order interactions. Third, a multi-granularity fusion branch is constructed to achieve progressive fusion of multi-scale features. Finally, the multi-branch representations are weighted and fused through a gating network, combined with the output results of a perceptron and a sigmoid function, and optimized using binary cross-entropy. This invention improves prediction performance and interpretability, and is applicable to scenarios such as drug discovery and target screening.

The application belongs to the technical field of biomaterial preparation, and particularly relates to a composite drug delivery system based on macrophage membranes and a preparation method and application thereof. The composite drug delivery system takes a lipid nanoparticle as a drug targeting delivery carrier, coats quercetin through an active phagocytosis mode, coats a macrophage membrane on the surface of the lipid nanoparticle, and constructs a quercetin lipid nanoparticle coated with a macrophage membrane (MCM@QU@LNP). The composite drug delivery system provided by the application can promote drug enrichment in RA lesions, improve local drug exposure, realize precise drug delivery in the RA part, has good biological safety, and reduces system toxicity.

The application provides application of a TAS2R4 agonist in preparation of a drug for treating and preventing diabetic nephropathy, and comprises that a bitter taste receptor 4 subtype (TAS2R4) can be used as a drug target point for treating and preventing diabetic nephropathy, and quinine is used as a TAS2R4 agonist. Specifically, mouse diabetic nephropathy induced by a chemical reagent and mouse podocyte cell line MPC cell damage caused by chronic high glucose are taken as research objects, it is found that mouse TAS2R4 agonist quinine has a prevention and treatment effect on diabetic nephropathy, has a protection effect on podocyte loss caused by high glucose, and has an activation effect on mouse kidney TAS2R4 molecular signal, and a possible molecular mechanism is discussed from the aspects of inhibiting NLRP3 inflammasome activation and NF-kappa B signal activation path, and theoretical basis and technical support are provided for prevention and treatment of diabetic nephropathy, other kidney diseases with inactivation of TAS2R4 molecular signal and other diseases by using TAS2R4 agonists including quinine.

The application discloses application of NAMPT as a target point in preparation of a medicine for treating uveitis, wherein the medicine contains a NAMPT inhibitor, the NAMPT inhibitor is FK866, and the NAMPT inhibitor is used for inhibiting expression or activity of NAMPT, thereby down-regulating CD4 + The Hif1a expression level of T cells reestablishes the Teff / Treg balance, and inhibits occurrence and development of uveitis, thereby providing a brand-new drug target for treatment of uveitis. Meanwhile, the application verifies that the NAMPT-HIF1a axis has conservation and potential treatment value in uveitis through experiments, proves that NAMPT can become a potential treatment target of uveitis, and proposes that a NAMPT inhibitor is used for preparing the medicine for treating uveitis, thereby laying a solid theoretical and experimental foundation for development of a new generation of targeted medicine for treating uveitis.

The invention relates to the field of biomedical research, and provides a lung cancer cell strain (H1299) capable of stably and low-expressing Integrin alpha6 protein and a construction method of the lung cancer cell strain (H1299). The preparation method comprises the following steps: designing and synthesizing an shRNA (short hairpin Ribonucleic Acid) sequence for specifically knocking down gene expression aiming at a human Integrin alpha6 gene, forming a double-chain fragment through annealing, and inserting the shRNA sequence into a pLKO.1-puro lentiviral vector by adopting a connection independent cloning (LIC) method, so as to construct a pLKO.1-ITG alpha6-shRNA recombinant plasmid. Furthermore, the recombinant plasmid and lentivirus packaging plasmids psPAX2 and pVSVG are co-transfected to an HEK293T cell by utilizing a lentivirus packaging system, and the lentivirus is produced by packaging. And infecting a target lung cancer cell strain H1299 by using the obtained lentivirus, and then carrying out puromycin resistance screening and continuous subculture to finally obtain the stable and continuous low-expression Integrin alpha6 protein H1299 cell strain. A fluorescence microscope, a real-time fluorescent quantitative PCR (Polymerase Chain Reaction) and an immunoblotting technology are used for verifying that the gene silencing efficiency of the Integrin alpha6 in the cell strain can reach more than 80%. The stable cell strain constructed by the invention provides a reliable and efficient tool cell model for researching the molecular mechanism of the Integrin alpha6 in the processes of occurrence and development, invasion and metastasis, energy metabolism, immune escape and the like of lung cancer, and also provides a new experimental material for screening antitumor drugs targeting the Integrin alpha6.