51 results about "CXCR4" patented technology

The present invention provides CXCR4 inhibitors of formula (I) and pharmaceutically acceptable salts thereof, as well as methods of using them in the treatment of neurological and CNS diseases, disorders, and conditions. The provided compounds are inhibitors of CXCR4 and are therefore useful for treating one or more disorders associated with CXCR4 activity. Thus, in certain embodiments, the present invention provides a method for treating a CXCR4-mediated disorder, comprising administering to a patient in need thereof a CXCR4 inhibitor described herein, such as a compound of formula I or a pharmaceutically acceptable salt thereof. Certain embodiments of the present invention are directed to the use of CXCR4 inhibitors that, when administered to a subject, cross the blood-brain barrier (BBB) ​​and enter the brain and central nervous system (CNS). JPEG2026502774000083.jpg3135

The application belongs to the technical field of biological medicine, and relates to application of a CXCL14 inhibitor in preparation of a drug for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the gender difference of abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and its receptor CXCR4, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress of abdominal aortic aneurysm, reduces the degree of collagen degradation and elastic fiber damage, and thus inhibits the pathological progress of abdominal aortic aneurysm. The application provides a new target and drug combination for precise treatment of male abdominal aortic aneurysm, and has clear clinical application value.

The application discloses double-gene engineered mesenchymal stem cells and application thereof, relates to the technical field of biological medicine. The double-gene engineered mesenchymal stem cells provided by the application co-express CXCR4 and TNFSF14 proteins, exhibit enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principle that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing its ligand SDF-1 (SDF-1 / CXCL12), and TNFSF14 (LIGHT) can interact with HVEM and LTbetaR receptors to promote the activation of T cells and NK cells, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects of insufficient targeting of natural MSCs and weak immune activation ability, and have excellent anti-tumor effect.

The application belongs to the technical field of biological medicine, and provides a CXCR4 high expression type iPSC-NK cell with enhanced bone marrow and tumor tissue homing ability, and a preparation method and application thereof. The cell takes pluripotent stem cells as starting cells, overexpresses a membrane-bound IL-15 and IL-15RA fusion protein gene and a CXCR4 receptor gene in the pluripotent stem cells; pluripotent stem cells stably expressing the target gene are obtained, and then iPSC-NK cells are obtained through induction differentiation. The membrane-bound IL-15 and IL-15RA fusion protein gene and the CXCR4 receptor gene are targetedly integrated into a safe harbor site of the induced pluripotent stem cell through a gene editing technology, so as to construct an iPSC cell strain stably expressing key proteins; the function-enhanced iNK cell is obtained through induction differentiation, and exhibits excellent bone marrow and various solid tumor tissue homing ability and persistent immune killing activity.

The present invention relates to a cell population of spiral ganglion neural progenitors (SGNPs) and methods how to isolate these cells from an in-vitro mixed cell population. The cell population expresses one or more markers, wherein the one or more marker is CXCR4, SUSD2, LPAR3, EPHA5, CHRNA3, REEP1, NPFFR2, SORCS3, NFASC, GABRB3, KCNB2, GRM8, DLL3, and / or KCNH8.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

This invention belongs to the field of protein engineering and biomedicine, and particularly relates to a water-soluble membrane protein, a recombinant vector, a recombinant host bacterium, and their modification methods and applications. The method involves the following steps: First, an interface mutant is constructed based on the SQTY code, and its water solubility and ligand binding ability are evaluated. If the requirements are not met, multiple low-impact transmembrane regions are screened, and after mutation modification, the interface mutant is introduced to construct a single-transmembrane combined mutant, whose water solubility and ligand binding ability are evaluated. If the requirements are still not met, the multiple low-impact transmembrane regions are combined in pairs, and the interface mutant is introduced to construct various double-transmembrane combined mutants, whose water solubility and ligand binding ability are evaluated, and the optimal double-transmembrane combined mutant is selected. This method rationally mutates CXCR4 in stages to achieve water solubility, minimizing changes to the protein's structure and other physicochemical properties, thereby maintaining or even enhancing its binding ability to the ligand CXCL12.

This application discloses a compound or a pharmaceutically acceptable salt thereof, said compound comprising a compound of formula (I) or a compound of formula (II). A radioactive element preparation comprising thereof and a radioactive element chelated therewith is also disclosed. Its use in the preparation of reagents targeting CXCR4, particularly CXCR4 tracers, more particularly in vivo CXCR4 tracers, or reagents that specifically bind to cells expressing CXCR4 is also disclosed. [Targeting Peptide-I]-Xaa1-X 1 (R 1 )L 1 -[Connector]-R x n1 (I), R x n1 -[Connector]-X 1 (R 1 )L 1 -Xaa1-[targeting peptide-II](II).

The invention relates to the technical field of biology, in particular to a method for modular assembly of artery blood vessel type organs and construction of tissue microcirculation of the artery blood vessel type organs. The method comprises the following steps: inducing human pluripotent stem cells to differentiate through a mesoderm stage to form an arterial specific vascular organoid module (AVO), and then carrying out modular assembly on the AVO in vivo or in vitro so as to quickly reconstruct a tissue microcirculation network with arterial characteristics. The obtained artery blood vessel organoid is uniform in form, the diameter of the artery blood vessel organoid is intensively distributed at about 200 microns, SOX17 and CXCR4 artery endothelial markers are expressed at the same time, and the artery blood vessel organoid has polarity and a complete basilar membrane. Transplanting experiments show that the organ can be integrated with host blood vessels in a short time, and ischemic tissue blood perfusion is recovered. The defects that existing organoid is irregular, difficult to splice, delayed in perfusion and the like are overcome, and a new strategy is provided for revascularization and acute ischemic disease repair.

The present application discloses a kind of compound for targeting CXCR4 and purposes thereof.The compound is shown in structure of formula (I) or its isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer or pharmaceutically acceptable salt.The compound of the present application connects ligand group (Ra and Rb) for targeting CXCR4 and chelating group Z by linker (L1-X-L2), which has good CXCR4 targeting and specificity, can be quickly imaged in a short time after administration, and can be used for diagnosing and treating CXCR4 overexpression diseases.

The present disclosure is based on a novel assay based on the determination of SDF-1 [alpha]-induced migration of CXCR4 primary human cells in the presence of an anti-CXCR4 polypeptide, correlating the degree of CXCR4 receptor occupancy (RO) of the anti-CXCR4 polypeptide with the efficacy of the anti-CXCR4 polypeptide. Migration inhibition as determined by an in vitro assay provides an alternative indicator of in vivo efficacy of the anti-CXCR4 polypeptide.

The invention provides a use of a marker or a combination thereof in preparation of a product for prediction, diagnosis or auxiliary diagnosis of measurable residual diseases, the measurable residual diseases occur after clinical complete remission of acute myelogenous leukemia patients, and the marker or the combination thereof comprises a C-X-C chemokine receptor 4 gene. According to the method, a multi-parameter flow sorting technology is adopted, leukemia cell populations are separated from bone marrow samples of patients in the first diagnosis stage and the AML MRD stage, and a sufficient number of residual disease cells are successfully captured through a single cell transcriptome sequencing technology. The CXCR4 low-expression cell is identified to be capable of being used as a common marker of an MRD cell, and is verified in a clinical AML patient specimen. And an innovative scheme is provided for MRD monitoring of AML patients lacking clear molecular markers. And meanwhile, a CXCR4 low-expression cell is provided as a function substitution model of the MRD cell, so that the technical limitation of insufficient residual cells in the traditional research is broken through, and a reliable research system is established for systematically exploring the biological characteristics of the MRD cell.

The present invention relates to NK cells with an improved ability to target and kill cancer cells and use thereof. Specifically, the present invention relates to: iPSC-based NK cells into which a chimeric antigen receptor targeting a specific cancer antigen, CXCR4 and CCR7 genes, which are chemokine receptors, and an IL-15 / IL-15Rα (IL-15RF) gene are introduced; and use thereof for treating cancer. The iPSC-based NK cells according to the present invention can not only directly target a specific cancer antigen by the introduced CAR, but can also activate NK cells and enhance the proliferation thereof by regulating intracellular signaling and tumor microenvironment by the introduced CXCR4 and CCR7 and the introduced IL-15RF. Therefore, the NK cells into which multiple genes are introduced, according to the present invention, can efficiently target and attack cancer cells, and thus can be effectively used for the treatment of cancer diseases.

The invention relates to the technical field of immune preparations, in particular to application of Forskolin or pharmaceutically acceptable salt thereof in preparation of a vaccine immunopotentiator. Aiming at the defects of vaccine immunomodulators in the prior art, the invention provides a novel method for enhancing the immune effect of a vaccine by using a natural plant extract Forskolin (as an adenylate cyclase activator), the Forskolin can promote high expression of CXCR4 by plasma cells to obviously enhance the homing ability, the residence ability and the service life of the plasma cells, so that the immune effect of the vaccine is enhanced. Therefore, the long-term immune response of the antibody is improved. The Forskolin directly targets the effector cytoplasm cells immunized by the vaccine, so that the potential safety hazard of the traditional technology is avoided, and meanwhile, more lasting and stable immune protection is provided.

The present invention relates to the systems and methods of identifying compounds to treat or prevent chronic obstructive pulmonary disorders (COPD). The present invention also provides compositions to treat or prevent COPD comprising modulators of one or more selected from the group consisting of: AC AN, ACTN1, ADAMTS4, ADRB2, AGER, AN06, AP3B1, AP0A1, ARRB1, ATP1A1, BCL2L1, BDKRB1, BRAF, CALCRL, CCL11, CDH1, CEACAM8, CHRM3, CHRNA1, CLU, COL10A1, COL12A1, COL14A1, COL4A2, COL6A1, COL6A3, COLGATE 1, CRH, CSK, CTSD, CTTN, CXCR1, CXCR4, CXCR5, FBN1, FGA, FGG, FHL2, FTH1, GNB1, GPIHBP1, GPR84, GPR97, GRM8, HAPLN1, H2BFS, HBB, HSP90B1, ICAM1, IGF1R, IL6, ITGA1, ITGAV, LAMA2, LAMA4, LRP1, LTBP1, MAPK3, MGAM, MMP1, MMP13, MMP3, MMP9, MYBPH, MYH10, MYH9, NMU, NR3C1, P4HB, PLCB3, PLAG2G7, POU2AF1, PPIB, PROK2, RUNX2, RXFP1, S100A12, S100P, SAA1, SDC2, SLC2A5, SMAD3, SPARCL1, SPP1, SYT13, TBX1, TF, TGFB2, THBS1, TIMP1, TLN1, TPM1, TPM2, TPM4, TSPAN14, TEN, TWIST2, VIM, and WT1, and methods of use thereof.

A herpes virus vector is provided with both transcriptional and translational control. Within various embodiments the herpes virus vector is based upon a modified herpes virus and has both ICP27 and ICP34.5 under control of a CEA promoter and miRNA-124 / 143, respectively, and deletion of at least one copy of terminal repeat long region is provided to increase safety without sacrificing efficacy. The herpes virus vector can also incorporate a virus-expressed cytokine cassette encoding IL-12, IL-15 / IL-15RA under the control of CXCR4 promoter.

The present application provides compositions and methods of use for treating, preventing or ameliorating diseases, disorders or conditions associated with chemokine receptors (e.g., CXCR4).

The invention discloses a primer blocker composition for detecting a macroglobulinemia Fahrenheit CXCR4 gene, the primer blocker composition comprises a primer group and a blocker, and the primer group comprises a forward primer group and a reverse primer group; the nucleotide sequence of the blocking agent is as shown in SEQ ID NO. 1; the nucleotide sequence of the reverse primer group is as shown in SEQ ID NO. 2; the nucleotide sequence of the forward primer group is as shown in SEQ ID NO. 3. The invention also discloses a kit containing the composition and a detection method. By accurately detecting the CXCR4 gene, the CXCR4 gene can be combined with other markers, and pathological diagnosis and molecular typing of WM are accurate; a plurality of CXCR4 high-frequency mutation sites of WM can be covered by a single reaction, and compared with a digital PCR method only capable of detecting a single site, the cost is reduced by more than 80%, and the method is suitable for being popularized in hospitals.

This invention provides a method for preparing and applying a class of Motixafortide-nitrogen mustard conjugates and their fluorescent probes, belonging to the fields of peptide preparation and biomedicine. This invention utilizes a solid-phase peptide synthesis method to covalently link the DNA alkylating agent nitrogen mustard with the CXCR4 targeting peptide Motixafortide, and further couple it with a fluorescent dye, successfully preparing a series of novel conjugates and their fluorescent probes. Experimental verification shows that the Motixafortide-nitrogen mustard conjugates and their fluorescent probes prepared in this invention can significantly enhance the antitumor activity and targeting of nitrogen mustard to tumor cells. Simultaneously, the rhodamine B-labeled dinitrogen mustard conjugate BCCR exhibits specific targeting of the CXCR4 receptor and dual targeting of the tumor cell nucleus. These conjugates enable real-time tracking of the entire process of tumor targeting, cell delivery, and nuclear localization, providing a powerful tool for efficacy evaluation and mechanism research, thus possessing promising clinical translational prospects and application value.

A multi-targeting compound, a pharmaceutical composition comprising or consisting of same, a kit comprising or consisting of the compound or pharmaceutical composition, and the use of the compound or pharmaceutical composition in the diagnosis or treatment of diseases characterized by abnormal expression of FAP, CXCR4, GRPR, and / or αvβ3.

The application discloses a novel preparation method and application of hybrid extracellular vesicles. The application combines endothelial cell-derived and neutrophil-derived vesicles with deferoxamine to develop a biological mixed nano-vesicle platform (DFO@HEVs) to solve the problem of diabetic wound healing. The dual-targeting system utilizes CXCR4-mediated endothelial cell homing and beta2 integrin-dependent inflammatory tropism to accurately deliver DFO to the wound site, DFO@HEVs activate HIF-1alpha / VEGF to restore vascular regeneration, inhibit ferroptosis through Nrf2 / GPX4 signaling, and reprogram macrophages into a pro-repair M2 phenotype, effectively breaking the oxidative stress-inflammation-ferroptosis cycle.

The invention discloses a bispecific bionic nanomaterial and a preparation method and application thereof, and belongs to the field of biological medicine.The bispecific bionic nanomaterial is composed of a marrow stromal cell membrane modified enzyme-loaded porphyrin covalent organic framework, an anti-CD3 antibody and an anti-PD-L1 antibody, the enzyme-loaded porphyrinyl covalent organic framework is loaded with glucose oxidase, and the antibody is anchored on a phospholipid bilayer of the enzyme-loaded porphyrinyl covalent organic framework modified by a cell membrane through a physical effect; the bispecific bionic nano material prepared by the invention can block a CXCR4 / CXCL12 axis and inhibit migration and adhesion of leukemia cells; according to the bispecific bionic nanomaterial, hydrogen peroxide generated by decomposition of glucose is converted into hydroxyl radicals for chemical kinetic treatment by utilizing peroxidase-like activity of a porphyrin-based covalent organic framework, and T cells are redirected to leukemia cells to play a killing role.

In various embodiments drug delivery vehicles and uses thereof are provided. In certain embodiments the drug delivery vehicles comprise: 1) a silicasome comprising a mesoporous silica nanoparticle coated with a lipid bilayer and further comprising a CXCR4 antagonist; or 2) a liposome comprising a lipid bilayer comprising where said liposome further comprises a CXCR4 antagonist. In certain embodiments the CXCR4 antagonists are selected from the group consisting of AMD3100, AMD3465, and AMD070.

The present invention provides methods of producing, from malignant pleural effusion, expanded populations of tumour tissue-resident T cell memory (Trm) like CD103+CD8+ T cells based on expression of GPR183 and CXCR4 or expression of LITAF, JUNB and PI3KR1. Also provided are uses of said cells as a medicament and as a prognostic marker.

The present invention relates to a method and composition for mobilizing cells from a subject by blocking CXCR4, beta-adrenergic receptors, GPCRs, or any combination thereof. In some embodiments, the cells are hematopoietic stem cells. In some embodiments, the method further comprises the administration of G-CSF. The present invention also relates to a treatment method, a method for qualifying a subject for treatment, and a method for preparing a subject for treatment by blocking CXCR4, beta-adrenergic receptors, GPCRs, or any combination thereof. In some embodiments, the cells are hematopoietic stem cells. In some embodiments, the treatment is for cancer. In some embodiments, CXCR4 is GPC-100. In some embodiments, the method further comprises the administration of G-CSF.

The present invention relates to the technical field of organic fluorescent molecules, and provides a targeted near-infrared fluorescent compound, and a preparation method therefor and the use thereof. The targeted near-infrared fluorescent compound has a structure as represented by formula I. S0456 near-infrared small molecules are modified on a CXCR4 inhibitor by means of an organic total synthesis method, thereby obtaining the targeted near-infrared fluorescent compound represented by formula I. The targeted near-infrared fluorescent compound has a good active targeting effect during the identification of CXCR4-overexpressing tumors, such as triple-negative breast cancer and head and neck squamous cell carcinomas; and the targeted near-infrared fluorescent compound retains the water solubility of a dye and specificity to tumor cells, and has the advantages of good water solubility, high fluorescence quantum yield, etc.

The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.

This invention provides a probe library and kit for detecting genetic risk gene mutations in viral infections, belonging to the field of gene detection technology. The probe library and kit designed in this invention achieve, for the first time, the simultaneous detection of all mutations in the following 51 genetic risk genes for viral infections: CARMIL2, CCL2, CD27, CD70, CIB1, CTPS1, CXCR4, CYBC1(C17orf62), DBR1, FCGR3A, FCHO1, ICAM1, IFIH1, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IL10, IL10RA, IL10RB, IL... The probe library and kit of this invention contain 18BP, IRF3, IRF7, IRF9, MAGT1, LIG1, MCM2, NOS2, OAS1, POLR3A, POLR3C, POLR3F, PRKCD, RASGRP1, SH2D1A, STAT1, STAT2, TBK1, TICAM1, TLR3, TLR7, TLR8, TMC6, TMC8, TNFRSF9, TRAF1, TRAF2, TRAF3, TYK2, UNC93B1, and XIAP. This invention's probe library and kit can be used for detecting genetic variations in the risk of viral infection in clinical settings, assessing an individual's genetic risk of viral infection, and has broad application prospects.

The invention relates to the field of biomedical engineering and regenerative medicine, in particular to a method for activating the homing potential of bone joints of stem cells induced by small molecules and application, and the homing potential of the stem cells is remarkably enhanced by adopting the synergistic effect of three core factors, namely SDF-1alpha, TGF-beta and vitamin D. Through induction treatment, the expression of stem cell surface homing related molecules CXCR4 and Integrin beta is remarkably improved, so that the directed migration and repair capability of the stem cell surface homing related molecules CXCR4 and Integrin beta to a damaged bone joint area is enhanced. In-vitro and animal experiment results show that the activated stem cells show a remarkable repairing effect in histological, functional recovery and iconography detection, the knee joint motion range and the cartilage thickness are remarkably improved, and the homing rate reaches 40%-60%. The method is simple and convenient to operate, does not need gene modification, provides a new cell treatment scheme for osteoarticular diseases, and has a wide clinical application prospect.