20 results about "CXCR4 antagonist" patented technology

The invention discloses a manganese dioxide albumin nano-composite and a preparation method and application thereof, the manganese dioxide albumin nano-composite is successfully synthesized in a water phase by utilizing a biomineralization strategy and using albumin as a biological template, and a CXCR4 antagonist can be further loaded to obtain a CXCR4 antagonistic nano-composite. The manganese dioxide albumin nanocomposite has good biocompatibility and biodegradability, provides a new thought for diagnosis and treatment of hepatic fibrosis with a safe and efficient drug delivery strategy, and has great potential in the aspect of clinical transformation.

The invention discloses an MMPs response type anti-tumor polypeptide CFK-16 and application thereof, and belongs to the technical field of biological medicine. The MMPs response type anti-tumor polypeptide CFK-16 is synthesized by taking FK-16 and CXCR4 antagonist CBP as a precursor, the MMPs response type anti-tumor polypeptide CFK-16 comprises a hydrophobic sequence FFY, and the anti-tumor polypeptide CFK-16 not only can induce tumor cell apoptosis, but also can form self-assembled nanofibers through triggering of MMPs highly expressed in tumor tissues and the hydrophobic sequence, so that accumulation of targeted tumors is achieved, and the anti-tumor effect is good. The curative effect of the polypeptide on a tumor part is enhanced, a remarkable anti-tumor effect is finally realized, and the polypeptide has a very good application prospect.

The present invention relates to methods for treating diseases by the in vivo gene editing of hematopoietic stem and progenitor cells (HSPCs), and in particular to the use of a CXCR4 antagonist to increase the efficiency of HSPC gene editing in vivo when administered prior to or in conjunction with administration of a gene editing system to a subject in need thereof.

The novel CXCR4 antagonist designed by the invention is composed of a novel CXCR4 antagonist 1, a novel CXCR4 antagonist 2 and a novel CXCR4 antagonist 3, which can be used in combination or independently, the three newly designed CXCR4 antagonists form a molecular architecture different from the existing CXCR4 antagonist, the three structural designs are the basis for realizing high affinity and specific antagonism on CXCR4, and the novel CXCR4 antagonist can be used as a novel CXCR4 antagonist. According to the present invention, the combination of the CXCR4 and the ligand thereof is highly specifically blocked, the activation of the downstream signal channel is effectively inhibited, and compared with the existing clinical use drugs, the significant advantages of the antagonistic activity, the synthesis difficulty and the safety are provided, and the key embodiment of the core treatment value is provided.

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 discloses a chitosan nanoparticle for inhalation administration, the chitosan nanoparticle comprises chitosan, and the chitosan is connected with a CXCR4 antagonist. The chitosan nanoparticle designed and prepared by the invention can interact with collagen through a hydrogen bond, has a mucous membrane adhesion characteristic, can increase the local concentration of a drug in a lung after aerosol inhalation, and can inhibit invasion and metastasis of tumor cells through an antagonistic CXCR4 / CXCL12 pathway.

The invention discloses an ergothioneine and achyranthes bidentata polysaccharide composition for inhibiting HPV and a preparation method of the ergothioneine and achyranthes bidentata polysaccharide composition, and relates to the technical field of biological medicines. The composition is prepared from the following components in parts by mass: 1 to 5 parts of ergothioneine, 3 to 10 parts of achyranthes bidentata polysaccharide, 0.2 to 1.2 parts of a CXCR4 antagonist, 0.5 to 2 parts of sodium hyaluronate, 10 to 20 parts of a polyhydric alcohol cosolvent and 60 to 80 parts of deionized water, wherein the CXCR4 antagonist has a specific structure as shown in formula 1. According to the composition, through targeted intervention of the CXCR4 antagonist, delivery network construction of achyranthes bidentata polysaccharides and stable synergy of ergothioneine, a multi-mechanism synergistic effect is achieved, and the inhibition effect on HPV infection and the preparation stability are improved.

A method for preparing and applying immobilized enzyme nanogels includes oxidized sodium alginate and enzymes are dissolved separately in deionized water, mixed uniformly, and reacted to obtain immobilized enzyme nanogels; the aldehyde groups in oxidized sodium alginate react with the amino groups in the enzymes, forming imine bonds to immobilize the enzymes; forming nano-scale cross-linked polymer-based particles with a three-dimensional network structure, resulting in the immobilized enzyme nanogels; the surface of immobilized collagenase nanogels is modified with CXCR4 antagonist peptides, which can specifically block CXCR4 on the surface of T cells; the Schiff base bonds can selectively break in the acidic microenvironment of tumors, leading to collagen degradation and reduced extracellular matrix density; the modification enhances the chemotaxis and infiltration of T cells into pancreatic cancer tissues and can inhibit the metastasis of pancreatic cancer.

The present invention relates to a composition comprising C-C motif chemokine ligand 5 (CCL5) for promoting the activation of bone marrow-derived stem cells. It is identified that, when CCL5, which is a niche-enhancing factor, is injected together with growth related oncogene beta (GROβ), which is known to promote the mobilization of hematopoietic stem cells from the bone marrow into peripheral blood, and AMD3100, which is a CXCR4 antagonist, the migration of hematopoietic stem cells from bone marrow to peripheral blood increases, and the engraftment rate also increases when the hematopoietic stem cells are injected into recipients undergoing bone marrow transplantation. Therefore, the CCL5 protein, GROβ, and the CXCR4 antagonist AMD3100 are provided as a composition for promoting the activation of bone marrow-derived stem cells, and thus bone marrow-derived stem cells activated thereby is provided as a novel therapeutic means for bone marrow diseases requiring bone marrow transplantation.

The present disclosure describes the use of immune modulators to promote nerve growth and regeneration, particularly in the context of nerve deficit stemming from trauma and disease. In particular, the disclosure provides for the use of CXCR4 antagonists, STAT3 activators, and an agent that increases levels of nitric oxide, either alone or in any combination of these drugs, in surgery performed to treat nerve deficit conditions, especially peripheral nerve deficit conditions caused by cut injury or tear injury, the method especially useful in bridging nerve gaps of 3 cm or longer.

The invention discloses a CXCR4 antagonist with a hydroxamic acid structure as well as preparation and application of the CXCR4 antagonist. The invention discloses a compound with a structure as shown in a general formula (II) or a pharmaceutically acceptable salt of the compound. In the formula (II), R1 is selected from # imgabs1, R2 is selected from # imgabs2, and L is an empty or C1-C6 saturated or unsaturated aliphatic hydrocarbon chain. The compound with the structure as shown in the general formula (II) and / or the pharmaceutically acceptable salt thereof are / is a multi-target derivative capable of synergistically realizing anti-tumor, anti-inflammatory and anti-depression effects.

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.

This invention discloses 20 compounds that can act as CXCR4 antagonists, their pharmaceutically acceptable salts, as well as methods for preparing these compounds, synthetic routes, and their use in preparing drugs for preventing and treating related diseases by inhibiting CXCR4. The compounds disclosed in this invention are excellent CXCR4 antagonists for the prevention and treatment of diseases such as inflammatory bowel disease.

The novel CXCR4 antagonist designed in the present invention consists of novel CXCR4 antagonist 1, novel CXCR4 antagonist 2, and novel CXCR4 antagonist 3, which can be used in combination or individually. The three newly designed CXCR4 antagonists constitute a molecular architecture different from existing CXCR4 antagonists. These three structural designs are the basis for achieving high-affinity and specific antagonism against CXCR4, thereby achieving highly specific blocking of the binding of CXCR4 to its ligand, effectively inhibiting the activation of downstream signaling pathways. Compared with existing clinically used drugs, their significant advantages in antagonistic activity, ease of synthesis and safety are the key manifestation of their core therapeutic value.

This disclosure is based on a novel assay that links the degree of CXCR4 receptor occupancy (RO) by anti-CXCR4 polypeptides to the efficacy of anti-CXCR4 polypeptides, based on the determination of SDF-1α-induced migration of primary human CXCR4 cells in the presence of anti-CXCR4 polypeptides. Inhibition of migration, measured by the in vitro assay, provides a surrogate for the in vivo efficacy of anti-CXCR4 polypeptides.

The invention discloses a preparation method of a CXCR4 antagonist drug Mavorixfor and an isoquinoline derivative thereof, which comprises the following specific operation procedures: dissolving isoquinoline or benzimidazole in acetonitrile, adding methanol, a multi-bipyridine cobalt catalyst, electrolyte and a proton source, reacting under the conditions of visible light irradiation and constant voltage, and separating and purifying to obtain the CXCR4 antagonist drug Mavorixfor and the isoquinoline derivative thereof. And carrying out C-N coupling on the obtained hydroxymethylation product and a drug intermediate through a Mitsunobu reaction, so as to prepare the CXCR4 antagonist drug Mavorixfor and the isoquinoline derivative thereof. The method has the advantages of easily available and cheap raw materials, simple steps, high atom utilization rate, no need of additional addition of a stoichiometric oxidant, and good application prospects.

This application provides isolated antibodies, and antigen-binding fragments thereof that specifically bind chemokine receptor 4 (CXCR4). These CXCR4 antibodies, or antigen-binding fragments thereof, have a high affinity for CXCR4, function to effectively block SDF-1 binding to CXCR4, thereby inhibiting forskolin stimulated cAMP with low nM IC50, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat CXCR4-associated disorders while avoiding the adverse side effects associated with the current CXCR4 antagonist therapies.

The present invention discloses a phenylboronic acid copolymer for reshaping the tumor immune microenvironment and its application. The phenylboronic acid copolymer is formed by copolymerizing phenylboronic acid (PBA), polymeric CXCR4 antagonist AMD3100, and cholesterol. First, the AMD3100 moiety is polymerized through a Michael addition reaction, and then PBA and cholesterol are further modified to obtain the copolymer. The phenylboronic acid copolymer of the present invention can self-assemble into ATP-hypersensitive nanogels, which can load chemotherapeutic drugs inside and synergistically deliver albumin nanoparticles through electrostatic adsorption outside, realizing ATP-sensitive hierarchical delivery. It can significantly inhibit the number and activity of TAMs in the tumor microenvironment, reduce the recruitment of Tregs, amplify the immune signals in the microenvironment, reshape the tumor immune microenvironment in multiple dimensions, and enhance the effect of anti-tumor immune response.

To provide CXCR4 antagonists binding CXCR4 more effectively and with an increased blood stability and pharmacokinetic properties.SOLUTION: Provided are EPI-X4 based peptides and derivatives thereof, peptide derivatives selected from a list of peptide derivatives with a sequence derived from the human serum albumin fragment EPI-X4, which bind to CXCR4 with about 1000-fold stronger efficiency than EPI-X4. The peptide derivatives comprise length variants as well as modifications by length variants, D-amino acids, coupling of fatty acids, cholesterol or polymers, acetyl substitutions of amino groups, aminations of carboxyl groups. Further provided are pharmaceutical compositions of the peptide derivative.SELECTED DRAWING: Figure 1-1