66 results about "Molecular targeting" patented technology

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

The invention provides an application of a super enhancer inhibitor JQ-1 in preparation of peripheral artery disease related drugs, relates to the technical field of biomedicine, and discloses a core effect of the super enhancer inhibitor JQ-1 in peripheral artery disease ischemia repair. The traditional Chinese medicine composition can significantly accelerate blood flow recovery of ischemic limbs, up-regulate mRNA and protein expression of a vascular marker CD31 in gastrocnemius muscle tissues, effectively increase vascular density and promote angiogenesis. Aiming at the defects of the existing treatment means in the aspect of ischemic tissue angiogenesis, the application provides a brand new molecular targeted treatment scheme for high-risk groups such as patients with diabetes-related peripheral artery diseases, and can significantly reduce the risk of lower limb amputation and the incidence rate of related cardiovascular adverse events such as coronary heart disease and stroke; the technical blank of specific targeted therapy of peripheral artery diseases is filled, a solid scientific basis and a key direction are provided for research and development of novel drugs, and the specific targeted therapy method has extremely high clinical application value and wide research and development prospects.

Anti-CLEC12A polypeptides typically include an amino acid sequence having at least 90% amino acid similarity to SEQ ID NO: 14. In certain embodiments, the anti-CLEC12A polypeptides can be incorporated into an anti-CLEC12A biologic. In some of these embodiments, the anti-CLEC12A biologic can be a bispecific killer cell engager (BiKE), a trispecific killer cell engager (TriKE), a tetraspecific killer cell engager (TetraKE), a pentaspecific killer cell engager (PentaKE), a bispecific T cell engager (BiTE), a trispecific T cell engager (TriTE), a tetraspecific T cell engager (TetraTE), a pentaspecific T cell engager (PentaTE), a chimeric antigen receptor, a whole antibody, an antibody-drug conjugate (ADC) molecule, a targeted delivery construct, or a labeling construct.

The invention belongs to the technical field of biological medicines, and particularly relates to application of dirithromycin in preparation of a product for treating LINC00516 high-expression lung adenocarcinoma. The invention discloses the effect of the long-chain non-coding RNA LINC00516 in abnormal activation of the lung adenocarcinoma cell cycle for the first time. Researches show that LINC00516 is directly combined with CDK1, the kinase activity of CDK1 is remarkably enhanced, and the inhibitory phosphorylation level of CDK1 is reduced, so that lung adenocarcinoma cells are driven to quickly enter a G2 / M phase, and tumor cell proliferation is accelerated. The invention further innovatively proposes that dirithromycin is used as an intervention means, and by blocking the combination of LINC00516 and CDK1, the activity of CDK1 is effectively reduced, and the proliferation capacity of tumor cells is inhibited. In-vivo and in-vitro experiments prove that the dirithromycin can obviously inhibit the growth of lung adenocarcinoma cells with high expression of LINC00516, so that a brand-new molecular targeting treatment strategy is provided for clinic.

Provided herein is technology relating to vaccines and particularly, but not exclusively, to compositions, methods, and uses of a mixture of immunogenic vaccine molecules comprising components for targeting the dimeric vaccine molecules to antigen-presenting cells and components for eliciting an immunogenic response, wherein the components for eliciting an immunogenic response preferably comprise at least three variants of an immunogenic protein, such as variants of immunogenic proteins obtained from three or more different strains of a pathogenic organism.

The present application relates to the field of biological medicine and clinical diagnosis, and more particularly, the present application relates to a polypeptide having binding affinity to AXL protein and application thereof; the polypeptide has binding affinity to AXL protein, and therefore can be used for detecting AXL protein, so that the polypeptide has diagnostic or therapeutic use as a drug or molecular targeting reagent.

The invention discloses an application of miR-26a-5p in preparation of a product for preventing, repairing or treating cell aging. According to the invention, miR-26a-5p is applied to preparation of products for preventing and treating cell aging for the first time, a brand new molecular intervention strategy is provided for cell aging resistance, and the problem of lack of targeted molecular targeting schemes in the prior art is effectively overcome. The miR-26a-5p can be used for remarkably regulating and controlling the expression of cell cycle key factors CDK1, p21, Ki67 and Lamin B1, so that the proliferation state and the aging process of cells are accurately intervened.

Targeting immunosuppressive B cell populations using bispecific or multivalent targeting molecules presents a potential pathway for therapeutic interventions that effectively modulate antitumor immune responses and improve therapeutic outcomes. Therefore, we provide engineered antibody-based therapeutics that can effectively and selectively target immunosuppressive B cell populations for the treatment of cancer. [Solution] A multispecific antibody is provided comprising a CD19 antigen-binding component configured to bind to CD19 and a CD38 antigen-binding component configured to bind to CD38, wherein the CD19 antigen-binding component comprises an antibody or an antigen-binding fragment thereof, and the CD38 antigen-binding component comprises an antibody or an antigen-binding fragment thereof.

The present invention addresses the problem of providing a novel combination therapy having a potent antitumor effect and few side effects. The present invention provides an antitumor agent containing zipalertinib or a salt thereof as an active ingredient and used so as to be administered to a cancer patient in combination with an additional antitumor agent, wherein the additional antitumor agent is at least one selected from the group consisting of molecular targeting agents, immune checkpoint inhibitors, and antibody-drug conjugates.

Methods, techniques, and kits are provided herein for purifying cells using molecular targeting, at a cellular or subcellular level. The techniques comprise labeling a biological sample comprising cells with a probe capable of producing a protective barrier. The barrier is deposited onto the surface of the labeled cells or structures, to protect and retain the biological material under the barrier. A micropurification solution is applied to the biological sample, wherein the micropurification solution degrades, digests, or otherwise processes cells not covered by the barrier, allowing isolation of the target cells. In some aspects, a plurality of probes, each specific to a different target, may be used. The techniques may be performed without the need for complex instrumentation involving microscopy.

The invention belongs to the field of molecular targeted therapy, and discloses a small-molecule inhibitor CTPI3 of a targeted mitochondrial citric acid transporter SLC25A1 and application of the small-molecule inhibitor CTPI3 in tumor therapy. On the basis of an existing inhibitor CTPI2 structure, molecular design is carried out through an induced fit docking (IFD) module of Schrdinger software, and CTPI3 is obtained. Experiments show that the median inhibitory concentration (IC50) of CTPI3 on acute myelogenous leukemia (AML) cell lines (such as Kasumi-1 and THP1) and primary AML cells is obviously lower than that of CTPI2, the synergistic effect of CTPI3 and Venetoclax is enhanced, the mitochondrial ATP yield is reduced, and the TCA cycle metabolite level is affected. Animal experiments prove that CTPI3 can significantly prolong the lifetime of AML model mice and reduce leukemia load (spleen weight is reduced, and bone marrow and peripheral blood GFPcells are reduced), and has no significant toxicity (liver, kidney and brain histopathology is normal). The invention provides an efficient and safe new candidate drug for SLC25A1 targeted therapy.

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

The invention provides a detection reagent for LXOL2 gene expression quantity and application of LXOL2 as a rheumatoid arthritis treatment target, and relates to the technical field of biological medicines. According to an extracted total RNA sequence, a specific PCR primer is designed and synthesized, an RT-qPCR technology and a sequencing method are utilized, the expression of the LXOL2 in human synovial fibroblast-like cells is found to be remarkably increased, it is proved that the LXOL2 can be applied to preparation of a preparation for auxiliary diagnosis, treatment or prognosis evaluation of rheumatoid arthritis, meanwhile, Si-LOXL2 small in interference with the gene is designed and synthesized, and the application prospect is wide. According to the present invention, the expression of the LXOL2 gene can be knocked down, the expression of pro-inflammatory factors TNF-alpha, IL-1beta and IL-6 can be significantly inhibited, the expression of anti-inflammatory factors TGF-beta can be promoted, and the gene can be used as the RA molecular targeting treatment tool;

The invention discloses a red light-pH dual-response targeted antibacterial and anti-inflammatory nanoparticle as well as a preparation method and application thereof. The nano-particle is prepared from the following raw materials: a porphyrin-zirconium metal organic framework carrier, an antibacterial agent, NO donor molecules and a targeting ligand, the mass ratio of the porphyrin-zirconium metal organic framework carrier to the antibacterial drug to the NO donor molecule to the targeting ligand is 1: (0.8-1.2): (0.3-1): (1-3). The red light-pH dual-response targeted antibacterial and anti-inflammatory nano-particle is of a layered composite structure of'carrier-functional molecule-targeted shell ', and has high efficiency, safety and practicability.

Disclosed is a multi-specific molecule targeting CD16A expressed on NK cells and HER2 or GPC3 expressed on tumor cells, enhanced by a complex formed by IL-15 and IL-15Rα contained in the multi-specific molecule. Also disclosed are polypeptides, compositions and methods relevant to the multi-specific molecule.

The present application provides a polypeptide with binding affinity to HPV18 E6 protein, taking the Z domain of staphylococcal protein A as a scaffold, randomly mutating the surface amino acid residues to simulate antibody binding sites, constructing a mutant library through phage display technology, screening the library through affinity with HPV18 E6 as a target antigen, and finally obtaining a polypeptide with high affinity to HPV18 E6 through a large number of screening work. Through in-depth research, the present application first discloses a polypeptide with binding affinity to the E6 protein of HPV18. In addition, the present application also provides the diagnostic or therapeutic use of the polypeptide as a drug or molecular targeting reagent.

The invention provides application of a super enhancer inhibitor JQ-1 in preparation of a medicine for treating wound healing disorder related diseases. Relates to the technical field of biomedicine, the promotion effect of the super enhancer inhibitor JQ-1 in wound healing and repairing is disclosed for the first time, the super enhancer inhibitor JQ-1 is competitively combined with BET protein bromodomain, combination of the super enhancer inhibitor JQ-1 and acetylated histone is blocked, and super enhancer driven gene transcription is inhibited. Skin regeneration can be obviously accelerated, the wound healing time is shortened, and the healing degree is improved. Aiming at the pain point that the existing wound healing therapy is limited in effect, the invention provides a brand-new molecular targeted therapy scheme for people, such as diabetic patients and old people, which are easy to cause abnormal wound healing, can effectively reduce serious sequelae, such as amputation, and provides a scientific basis and a key direction for developing a novel medicine for promoting wound healing; the technical blank in the related treatment field is filled up, and important clinical application value and research and development prospects are achieved.

The invention belongs to the technical field of biological medicine, and provides a novel gold nanoparticle-based targeting preparation as well as a preparation method and application thereof. The targeting preparation provided by the invention contains a gold nanoparticle core, a connecting molecule, a targeting ligand and a therapeutic agent, the connecting molecule and the targeting ligand sequentially modify gold nanoparticles, the therapeutic agent is loaded at the drug loading capacity of 1-50wt%, and the mass ratio of the targeting ligand to the gold nanoparticles is (1: 5)-(1: 100). The targeting preparation provided by the invention can efficiently cross the blood brain barrier, obviously reduce Abeta deposition in the brain, is high in enrichment degree of a targeting region in the brain, can down-regulate miR-146a-5p to inhibit neuroinflammation, and can be used for treating neurodegenerative diseases.

Methods, techniques, and kits are provided herein for purifying cells using molecular targeting, at a cellular or subcellular level. The techniques comprise labeling a biological sample comprising cells with a probe capable of directing the deposition of a hydrophobic protective barrier. The hydrophobic protective barrier is deposited onto the surface of the labeled cells or structures, to protect and retain the biological material under the barrier. A micropurification solution is applied to the biological sample, wherein the micropurification solution dissolves, degrades, digests, or otherwise processes cells not covered by the barrier, allowing for; 1) isolation and collection of the target cells for molecular analysis, 2) isolation and collection of the non-target cells for molecular analysis, 3) removal for the purpose of disposing of the non-target cells. In some aspects, a plurality of probes, each specific to a different target, may be used. The techniques may be performed without the need for complex instrumentation involving microscopy.

The invention provides a small peptide for preventing and treating colon cancer and application thereof, and belongs to the technical field of biological medicine. Through structural simulation and functional verification, a polypeptide capable of specifically inhibiting G3BP1 lactylation in colon cancer cells in a targeted manner is screened out. The polypeptide inhibits the lactic acid modification level of G3BP1 by simulating a G3BP1 lactic acid recognition site and competitively combining with lactic acid enzyme, so that the G3BP1 mediated autophagy process is blocked, and finally proliferation and migration of colon cancer cells are inhibited. In-vitro cell experiments (including cell proliferation, migration and autophagy level analysis) and in-vivo transplantation tumor animal experiments prove that the oligopeptide can significantly inhibit growth and tumor formation of colon cancer cells. The discovery provides a new strategy and candidate drug molecules for molecular targeted therapy of colon cancer.

The present invention provides a method for efficiently producing lipid particles that contain an active component and in which the surfaces of the lipid particles are conjugated with a ligand specific to a target cell. The method for producing lipid particles with a ligand conjugated to the surface thereof includes: (1) a step for mixing an organic solvent phase (a) containing a lipid component, an aqueous phase (b) containing an active component, and an organic solvent phase or an aqueous phase (c) containing a molecule (targeting lipid molecule) in which a ligand specific to a target cell and a lipid are covalently bonded; and (2) a step for purifying the mixture obtained in step (1).

Disclosed herein are compositions and methods for deploying interventional agents into constrained biological states using non-crystalline amorphous iron oxide nanoparticles (NAIONPs). The NAIONPs comprise coordination-stabilized, aqueous colloidal dispersions lacking long-range crystalline order and presenting surface-accessible coordination sites for reversible or covalent association with one or more interventional agents. The compositions are configured to modify the biological context in which an interventional agent is presented, enabling functional engagement of agents whose deployment is limited when administered in isolation due to factors including impaired biodistribution, reduced stability, stress sensitivity, immune-mediated clearance, altered cellular responsiveness, or non-optimal exposure conditions. Interventional agents may include polynucleotides, peptides, proteins, small molecules, targeting moieties, radiologic agents, or combinations thereof. The disclosed compositions and methods are applicable to in vivo, ex vivo, and in vitro biological systems, including oncologic disease states such as primary tumors, metastatic disease, hematologic malignancies, and treatment-refractory cancers.

The application discloses application of a PI3K-gamma-delta signal path inhibitor in preparation of a product for treating central nervous system leukemia and the product, and solves the technical problem that the prior art lacks a molecular targeting product for acute lymphoblastic leukemia with CNSL which has better effect. The application comprises: application of the PI3K-gamma-delta signal path inhibitor in preparation of a product for treating acute lymphoblastic leukemia with central nervous system leukemia, and application of the PI3K-gamma-delta signal path inhibitor in preparation of a product for inhibiting proliferation, invasion and migration of acute lymphoblastic leukemia with central nervous system leukemia. The application also comprises a product of the PI3K-gamma-delta signal path inhibitor. The application discloses that central nervous system leukemia is closely related to an expression level of MSLN, and the PI3K-gamma-delta signal path inhibitor can inhibit the infiltration degree of acute lymphoblastic leukemia with central nervous system leukemia by reducing the expression level of MSLN, and prolong the survival time.

The invention discloses an anti-tumor nano-particle for photodynamic-targeted combined treatment as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The anti-tumor nanoparticles for photodynamic-targeted combined treatment comprise an amphiphilic polymer, and the tail end of a hydrophilic chain link in the amphiphilic polymer is modified with a photosensitizer; and the amphiphilic polymer modified with the photosensitizer is loaded with a molecular targeting drug. The anti-tumor nano-particles for photodynamic-targeted combined treatment are enriched at a focus part after being administrated by a system, generate a photodynamic effect under the irradiation of near-infrared light, and are combined with a molecular targeted drug to inhibit a PI3K / AKT signal channel and jointly inhibit the growth of EGFR mutant tumor cells, so that the anti-tumor effect is enhanced; the photosensitizer and the molecular targeting drug used in the invention are clinically used drugs, and have good biological safety and great clinical transformation potential.

The invention belongs to the technical field of biomedical engineering and cell therapy, and particularly relates to a preparation method of a mesenchymal stem cell exosome capable of improving an anti-inflammatory function. The core is a collaborative design of composite biochemical pre-stimulation and inflammatory microenvironment response type three-function targeting anchoring. A tumor necrosis factor-alpha with a concentration of 5-8 ng / mL, a resveratrol derivative with a concentration of 2-5 [mu] mol / L and glutathione with a concentration of 10-20 [mu] mol / L are adopted for reverse synergistic pre-stimulation, such that an anti-inflammatory pathway is activated; a vascular cell adhesion molecule-1 targeting domain-matrix metalloproteinase-9 sensitive connecting arm-LL-37 anti-inflammatory domain fusion polypeptide is anchored, so that precise targeting and response release are realized. According to the method, the problems of insufficient anti-inflammatory activity, poor targeting and off-target of the exosome are solved, the enrichment amount of an inflammatory site is increased by 2.5-4 times, the TNF-alpha inhibition rate reaches 90%-95%, and the exosome is suitable for treating inflammatory diseases.

Disclosed herein are modifications of polynucleic acid molecules such as inhibitory polynucleic acid molecules and pharmaceutical compositions comprising modified polynucleic acid molecules. Further, provided herein are methods for utilization of modified polynucleic acid molecules as well as methods for suppressing an expression of gene targeted by the modified polynucleic acid molecules.

The present disclosure provides a modified bispecific molecule that targets (a) a tumor-specific mutant peptide or mutation-associated neoantigen (MANA) presented by human leukocyte antigens (HLA) on the surface of target cancer cells; and (b) a surface protein (e.g., CD3) expressed on effector immune cells (e.g., T cells), as well as a method of using the molecule in cell therapy to diagnose, prevent, and / or treat human diseases including cancer. The bispecific molecule is modified to additionally include domain orientation modifications, linker modifications, and functional moieties including, e.g., Fc fragments, serum albumin, and / or polyethylene glycol (PEG) groups, which can improve efficacy, therapeutic index, half-life, and ease of manufacture while maintaining functionality and specificity in the treatment of diseases such as cancer.

The application belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical use of a Hedgehog pathway inhibitor in preventing and treating vascular remodeling and restenosis after an arterial bypass operation and improving the survival rate of a coronary heart disease patient after the arterial bypass operation. The abnormal proliferation of smooth muscle cells driven by endothelial cell activation can be obviously inhibited by the Hedgehog pathway inhibitor GDC-0449 intervention, and the inflammatory reaction can be effectively reduced. In the in-vivo experiment, the local application of GDC-0449 to the bypass artery can significantly relieve the remodeling and stenosis of the bypass artery, and provide a theoretical basis and strong support for the molecular targeted treatment strategy of the vascular remodeling and failure after the arterial bypass operation.