53 results about "Binding inhibition" patented technology

The invention provides a preparation method and application of an engineered MXene nano-enzyme capable of realizing antioxidant and anti-inflammatory sequential treatment of acute kidney injury, and the preparation method is characterized in that an MXene nanosheet is used as a carrier, and an artificial nano-enzyme adaptive to AKI specific treatment is constructed through engineering modification. Specifically, firstly, the biocompatibility and the biological stability of the MXene nanosheet are improved through surface modification of PEG, then the surface modification of ac5a aptamer and magnesium ions is carried out, and the MXene engineering nano enzyme is endowed with active targeting property and sequential therapeutic property. The engineered MXene nano-enzyme can be quickly accumulated in the kidney after AKI, is anchored and combined with c5a, inhibits complement activation, eliminates overload ROS, releases Mg < 2 + > after reaction degradation, further inhibits an MAPK / NF-kappa B pathway, promotes M2 polarization of macrophages, regulates inflammation progress, and finally realizes maximum inhibition of AKI.

The invention relates to an application of a bioactive peptide YPFPGPIH derived from bovine casein in the aspect of anti-inflammation or immunoregulation. The peptide can be combined with TLR2 and TLR4 to inhibit the activation of NF-kappa B and MAPK signal channels, so that the levels of inflammatory factors such as IL-1beta, TNF-alpha and NO are remarkably reduced, the expression of IL-10 is up-regulated, and inflammation balance regulation is realized; the body inflammatory response is improved, and the immune organ injury is recovered. The peptide can be used for preparing anti-inflammatory drugs, immunomodulatory functional foods and nutritional supplements, and has good safety and application prospects.

The invention discloses recombinant XVII type collagen with an anti-inflammatory effect and a preparation method of the recombinant XVII type collagen, and belongs to the technical field of protein engineering. The recombinant XVII type collagen provided by the invention comprises a plurality of repetitive units, and the repetitive units are as shown in SEQ ID NO. 1. Compared with natural XVII type collagen, the recombinant XVII type collagen is smaller in molecular weight, more stable and capable of being directly used for product production; meanwhile, the recombinant XVII type collagen disclosed by the invention can be combined with an inflammatory factor receptor to inhibit activation of a signal channel, so that the anti-inflammatory activity is improved, and therefore, the recombinant XVII type collagen disclosed by the invention can be used as a core active component to be applied to preparation of anti-inflammatory related products, and has a relatively high development prospect.

The invention relates to the technical field of biological medicines, in particular to a preparation method of an inhibitor targeting a MAX-PD-L1 promoter specific binding motif and a double-target inhibitor, through ChIP-seq and site-directed mutagenesis experiments, a core binding motif of MAX and a PD-L1 promoter, such as 5 '-CAC [GA] TG-3', is defined, it is ensured that the inhibitor only targets a key site of MAX-PD-L1 interaction, and the activity of the MAX-PD-L1 promoter specific binding motif is improved. The off-target effect is avoided, and a high-specificity target spot is provided for subsequent inhibitor design. The cell permeability of the DNA aptamer screened based on the specific binding motif is improved after cholesterol modification, and the affinity of the DNA aptamer is obviously higher than that of a traditional antibody. A small molecule compound virtually screened through a molecular docking model is optimized through hydrogen bond and hydrophobic interaction, and then the binding affinity with MAX is improved. After treatment with the inhibitor, the combination inhibition rate of MAX and the PD-L1 promoter is high, the transcriptional activity of PD-L1 is obviously reduced, the killing rate of T cells to tumor cells is also improved, and immune escape is effectively blocked.

The present disclosure relates to Ku-DNA binding inhibitor compounds, pharmaceutical compositions containing the compounds, and methods of using such compounds to treat cancer.

The purpose of the present invention is to provide an antibody against sPLA2-XIIA and a pharmaceutical composition containing the same. The present invention provides: an antibody or an antigen-binding fragment thereof that binds to sPLA2-XIIA, wherein the antibody or antigen-binding fragment thereof inhibits the enzymatic activity of sPLA2-XIIA and inhibits induction of differentiation of naïve T cells into Th17 cells; and a pharmaceutical composition containing the antibody or antigen-binding fragment thereof. The pharmaceutical composition of the present invention can be used, for example, for treating Th17-related diseases or cancer.

The invention relates to the technical field of medicines, in particular to application of benzbromarone in preparation of antithrombotic drugs. The research finds that benzbromarone clinically used for treating hyperuricemia can be combined with HSP47 on platelets to inhibit the interaction between the HSP47 and collagen so as to reduce platelet activation and thrombosis, which prompts that benzbromarone is an HSP47 inhibitor with an anti-platelet effect; benzbromarone has the effects of inhibiting mouse common carotid artery thrombosis and relieving cerebral ischemia reperfusion injury. Experiments finally confirm that benzbromarone can inhibit formation of common carotid artery thrombosis, does not affect the blood coagulation function, is low in cytotoxicity, has the drug effect similar to that of aspirin and clopidogrel which are commonly used at present, and can become an effective and safe therapeutic drug for cerebral arterial thrombosis.

Provided are an anti-ST2 antibody and a pharmaceutical composition. Specifically provided is an anti-ST2 antibody or an antigen-binding fragment thereof. The anti-ST2 antibody comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region comprises HCDR1 to HCDR3, and the light chain variable region comprises LCDR1 to LCDR3, wherein the amino acid sequence of HCDR1 is as shown in SEQ ID NO: 1, the amino acid sequence of HCDR2 is as shown in SEQ ID NO: 2, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO: 3; and the amino acid sequence of LCDR1 is as shown in SEQ ID NO: 4, the amino acid sequence of LCDR2 is as shown in SEQ ID NO: 5, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO: 6. The antibody can bind to human ST2, block the binding of human IL-33 to ST2, and inhibit the activation of downstream signaling pathways of a human IL-33 / ST2 pathway.

The invention discloses application of 1, 5-anhydro-D-sorbitol (1, 5-anhydroglaucitol, called 1, 5-AG for short) in inhibition of activation of NLRP3 inflammasomes, and particularly discloses application of 1, 5-anhydro-D-sorbitol (1, 5-AG for short) in inhibition of activation of NLRP3 inflammasomes. The invention relates to an application of 1, 5-anhydro-D-sorbitol in preparation of a medicine for inhibiting activation of NLRP3 inflammasomes, in particular to an application of 1, 5-anhydro-D-sorbitol. The NLRP3 inflammasome activation related diseases are selected from septicaemia induced by LPS, gouty arthritis induced by MSU, non-alcoholic fatty liver disease, systemic inflammatory response syndrome or inflammatory bowel disease. The 1, 5-AG is combined with an NATCH structural domain of the NLRP3 protein, so that the interaction between the 1, 5-AG and NEK7 and ASC is inhibited. The invention relates to an application of 1, 5-anhydro-D-sorbitol in preparation of functional food for inhibiting activation of NLRP3 inflammasomes. The 1, 5-AG is natural in source, high in oral bioavailability and high in safety, and has the advantage of being further developed into inflammation regulation drugs or dietary supplements.

The present invention provides an antibody or its antigen-binding fragment capable of binding to interleukin-31, as well as a method for producing the same and its use. The antibody or its antigen-binding fragment has high affinity and activity, and suppresses canine pruritic diseases, particularly canine atopic dermatitis, by blocking the binding of IL-31, especially canine IL-31, to its receptor.

The present application relates to the field of agricultural chemistry and environmental protection, in particular to a kind of with homogentisic acid solanonyl transferase (HST) as molecular target inhibitory compound and its application.A kind of with homogentisic acid solanonyl transferase as molecular target inhibitory compound, it is characterized in that: compound is the compound shown in the following structure, in the formula, R1, R2, R3 And R4 Respectively Br.The compound has significant inhibitory effect on phytoplankton growth at low concentration, and shows strong herbicidal effect on weeds such as eustreptosin and portulaca oleracea.The AlphaFold prediction analysis further confirms that these compounds inhibit the synthesis of plastoquinone by binding with HST, thereby effectively interfering with photosynthesis.The present application can be applied to algae and weed control in agriculture and aquaculture, and has wide application prospect.

This invention discloses an HBB-derived peptide and its use in the preparation of drugs for treating tumors. The HBB-derived peptide comprises a combination peptide consisting of a polypeptide with amino acids 30-40 at the N-terminus of HBB (as shown in SEQ ID NO:2) linked to a transmembrane peptide TAT (as shown in SEQ ID NO:3). The combination peptide is formed by modifying its N-terminus or C-terminus, through amino acid deletion, substitution, cyclization, or chiral conversion. Specifically, the amino acid sequence of this HBB-derived peptide, as shown in SEQ ID NO:1, is composed of a polypeptide with amino acids 30-40 at the N-terminus of HBB linked to a transmembrane peptide TAT. It can specifically block the binding of HBB to NDUFAF5, inhibit the proliferation of chemotherapy-resistant lung cancer cells and tumor growth, and reverse chemotherapy resistance, thus possessing significant clinical application value.

The invention belongs to the technical field of biological medicine, and particularly relates to application of a PRMT5 inhibitor CNI3 in promoting P-gp ubiquitination degradation and reversing tumor multidrug resistance, and the compound can be used as an active component to be prepared into various dosage forms. Experiments prove that the CNI3 can remarkably reverse the drug resistance of breast cancer caused by P-gp to doxorubicin (DOX). The action mechanism comprises the following steps: competitively combining P-gp outside cells to inhibit the excretion function of the P-gp on DOX; the PRMT5 is inhibited in cells, so that the stabilizing effect of the PRMT5 on the P-gp is reduced, and the ubiquitination degradation of the P-gp is promoted. CNI3 has small toxic and side effects on normal tissue cells and good safety, and has application potential in preparation of drugs for reversing multidrug resistance.

The invention belongs to the technical field of medicines, and particularly relates to application of a pigment epithelium-derived factor (PEDF) in synergistically enhancing a hepatocyte growth factor (HGF) in resisting pulmonary arterial hypertension (PH). Research finds that the HGF can improve pulmonary artery remodeling in PH, but can aggravate vascular leakage through a VEGF / VEGFR2 pathway. The PEDF can be combined with VEGFR2 (vascular endothelial growth factor receptor 2) to inhibit VEGF-induced endothelial cell activation and permeability increase. Meanwhile, a specific region of the PEDF is combined with the VEGFR2 under the action of a hydrogen bond and the like, and a derivative peptide fragment of the PEDF can block a VEGF / VEGFR2 signal. Compared with single HGF, cotransfection of the PEDF and the HGF can better inhibit angiogenesis and leakage and delay PH progress. Researches prove that the PEDF counteracts the leakage promoting side effect of the HGF through specific binding with the VEGFR2, and a theoretical basis is provided for developing a PH treatment strategy of the HGF combined with the PEDF derived peptide.

The present application relates to the technical field of biological medicine, and particularly relates to a method for preparing a new coronavirus and ACE2 receptor binding inhibitor drug by using a small molecule compound. Specifically, by using a virtual screening method in computer-aided drug design, including applying an artificial intelligence model, a molecular docking test and a molecular dynamics simulation experiment, 5 candidate inhibitors with good binding affinity and good selectivity to an ACE2 binding site are screened from a public database of small molecule compounds, and pharmacokinetics and toxicology properties of the candidate inhibitors are evaluated, so that a new use of the small molecule compounds for research and development of a new coronavirus infection drug is disclosed.

This invention belongs to the field of biomedicine and relates to an anti-ST2 antibody and a pharmaceutical composition. Specifically, this invention relates to an anti-ST2 antibody or its antigen-binding fragment, wherein the anti-ST2 antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising HCDR1 to HCDR3, and the light chain variable region comprising LCDR1 to LCDR3, wherein: the amino acid sequence of HCDR1 is as shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is as shown in SEQ ID NO:2, and the amino acid sequence of HCDR3 is as shown in SEQ ID NO:3; and the amino acid sequence of LCDR1 is as shown in SEQ ID NO:4, the amino acid sequence of LCDR2 is as shown in SEQ ID NO:5, and the amino acid sequence of LCDR3 is as shown in SEQ ID NO:6. The antibody of this invention can effectively bind to human ST2, block the binding of human IL-33 to ST2, and inhibit the activation of downstream signaling pathways in the human IL-33 / ST2 pathway, showing good application prospects.

This invention discloses a pyrrolobenzene derivative compound, its preparation method, and its pharmaceutical application, belonging to the field of chemical pharmaceutical raw materials and formulation manufacturing technology. The compound has the structure shown. This compound specifically binds to the SGLT-2 protein through a pyrrolobenzene conjugated system, inhibiting its glucose transport function and affecting the IC50 of SGLT-2. 50 Values ​​range from 15 to 105 nM. Suitable for preparing drugs to treat non-alcoholic liver disease, solid tumors, hematological malignancies, and autoimmune diseases, especially effective against abnormal glucose and lipid metabolism in hepatocytes and energy deprivation in tumor cells. The compound possesses enhanced metabolic stability due to its deuterated group and can be formulated into tablets, capsules, injections, and other dosage forms.

The application discloses application of SGI-7079 in treating FLT3 mutant acute myeloid leukemia. The application research shows that SGI-7079 can be stably combined with FLT3, inhibit the phosphorylation level of FLT3 and downstream STAT5, AKT and ERK, and induce G1 phase arrest and cell apoptosis. In vitro, SGI-7079 has strong inhibitory effect on FLT3-ITD and drug-resistant mutant cells; in a FLT3-ITD mouse model, SGI-7079 can significantly reduce leukemia load and prolong survival, and shows better curative effect than existing drugs on drug-resistant mutations such as F691L and D835Y. Meanwhile, SGI-7079 also has significant inhibitory effect on primary cells of FLT3-ITD positive patients. It is shown that SGI-7079 can be used as a new drug candidate for treating FLT3 mutation and drug-resistant AML, and provides a new direction for optimizing targeted therapy strategy.

The invention relates to the technical field of biology, in particular to application of multi-ligand glycan-4 to regulation and control of intercellular function of macrophages and renal fibrosis. According to the application, the inhibitor for inhibiting the binding effect of the binding areas between the multi-ligand glycan-4 and the phagocytosis and cell movement protein 1 is used for preparing the accelerant for promoting the interburial function of the macrophages. The application is based on earlier-stage research finds that the platelet reaction protein 1 is combined with a multi-ligand glycan-4 receptor on the surface of macrophages, meanwhile, the platelet reaction protein 1 can promote combination between the multi-ligand glycan-4 and phagocytosis and cell movement protein 1, and the interburial function of the macrophages is inhibited. And an animal model of knocking down the multi-ligand glycan-4 can delay the progress of renal fibrosis. Therefore, the multi-ligand glycan-4 can regulate and control the cellular burial function of the macrophages and delay the process of renal fibrosis at the same time, and the blank that the cellular burial function of the targeted macrophages is applied to renal fibrosis treatment in the prior art is filled.

To provide an antigen-binding protein which binds to a membrane-bound target and can be internalized. Also provided is an immunoconjugate comprising the antigen binding protein and a cytotoxic agent.SOLUTION: Provided is an antigen binding protein that specifically binds to BCMA and inhibits the binding of BAFF and / or APRIL to BCMA, wherein the antigen binding protein is capable of binding to Fc γ RIIIA or is capable of Fc γ RIIIA-mediated effector function and is capable of internalization.SELECTED DRAWING: Figure 1

The invention provides application of a compound inhibitor targeting a G protein coupled receptor ADGRE1, the compound inhibitor is called ADGRE1-i for short, and the molecular formula of the compound inhibitor is C27H22ClN3O3. According to the application, ADGRE1-i is applied to preparation of drugs for treating diseases caused by high expression of ADGRE1, the diseases caused by high expression of ADGRE1 comprise leukemia, and the leukemia comprises acute leukemia, chronic leukemia, hair cell leukemia and juvenile lymphocytic leukemia. The ADGRE1-i inhibits the activation of the ADGRE1 protein and the activation of downstream signal protein through the combination of the targeting interference ligand and the ADGRE1 protein, inhibits the proliferation of leukemia cells, and significantly inhibits the proliferation of AML cells.

The application discloses a salicylaldehyde derivative and application thereof. The compound and pharmaceutically acceptable salt and ester thereof can inhibit the combination of STAT3 and phosphorylated polypeptide, and achieve the anti-tumor purpose. The salicylaldehyde derivative can be combined with the SH2 domain of target protein STAT3, and inhibit the combination of the target protein and phosphorylated polypeptide. Compound 25 shows good competitive inhibition activity. In the anti-proliferation activity of pancreatic cancer cells in vitro, the compound 25 has sub-micromolar anti-proliferation activity of pancreatic cancer cells, and can induce cancer cell apoptosis. In addition, the compound 25 can significantly inhibit the phosphorylation of STAT3 705 sites and 727 sites, can inhibit the proliferation of various tumor cells in vitro, and has low toxicity to normal cells. Therefore, the compound can be used for preparing a STAT3 inhibitor, and used for preparing a medicine for preventing and / or treating diseases related to tumors.

The invention discloses an application of a mikania micrantha extract in preparation of a medicine for antagonizing TRPA1 and / or TRPV1 receptors. The research shows that the mikania micrantha extract has the effect of antagonizing a TRPA1 receptor or a TRPV1 receptor, also has the activity of antagonizing the TRPA1 receptor and the TRPV1 receptor, and can improve the symptom reaction of a model animal constructed by a specific TRPA1 receptor stimulant or a TRPV1 receptor stimulant, block the combination of the stimulant and the receptor, and inhibit the stimulant from playing a biological effect. Meanwhile, both the volatile oil extract and the aqueous extract of the mikania micrantha have better antagonistic effects which are equivalent to those of positive drugs, and have better antagonistic activity as a transient receptor potential (TRP) receptor antagonist, so that more methods and bases are provided for preparing more natural, safe and efficient drugs for antagonizing TRPA1 and / or TRPV1 receptors.

This disclosure pertains to the field of biomedicine, specifically relating to TL1A antibodies and their applications. The antibody or its antigen-binding fragment disclosed herein can bind to TL1A, block the binding of TL1A to DR3, inhibit TL1A-induced TF-1 cell apoptosis, inhibit TL1A-induced NF-κB signaling pathway activation, and inhibit TL1A-induced IFN-γ expression in blood cells.

A recombinant vector, a lentivirus, a lung-exempt MSLN CAR-T cell, and an anti-tumor agent are provided. The recombinant vector includes a first nucleotide sequence, a second nucleotide sequence, and a third nucleotide sequence, the first nucleotide sequence encodes a mesothelin (MSLN)-binding domain, the second nucleotide sequence encodes a leukocyte immunoglobulin-like receptor (LIR-1), and the third nucleotide sequence specifically binds to a lung-highly-expressed molecule. The lentivirus is constructed using the recombinant vector. The lung-exempt MSLN CAR-T cell is constructed using the recombinant vector or the lentivirus. When the lung-exempt MSLN CAR-T cell enters lung tissue, the second nucleotide sequence binds to the lung-highly-expressed molecule through the third nucleotide sequence, inhibiting the killing function of CAR-T to avoid pulmonary toxicity; when the lung-exempt MSLN CAR-T cell infiltrates tumor tissue, the second nucleotide sequence is inactivated, activating CAR-T cells to kill tumor cells, offering the advantages of precise therapy and low side effects.

The present disclosure pertains to compositions, methods, and kits for improving the rate of double-strand break (DSB) repair by homology directed repair (HDR) through inhibition of 53BP1 mediated DNA end protection in combination with inhibition of microhomology-mediated end joining (MMEJ), or alternatively in combination with inhibition of non-homologous end joining (NHEJ), or in combination with inhibition of both MMEJ and NHEJ

This disclosure relates to the discovery that a G12V mutant of KRAS (hereinafter KRAS G12V) binds to JAK1, i.e., the existence of a KRAS G12V and JAK1 binding interaction. In certain embodiments, this disclosure relates to methods of disrupting the KRAS G12V and JAK1 interaction reversing KRAS G12V induced immune escape by cancer cells utilizing agents that prevent the binding of JAK1 to KRAS G12V.

The present invention relates to a novel polypeptide that binds to MLH1 to inhibit its interaction with PMS2 and the formation of the MutLα complex, thereby enhancing prime editing efficiency, and uses thereof for prime editing. The polypeptide according to the present invention binds to MLH1 protein to inhibit the formation of a complex with PMS2, resulting in a significant improvement in prime editing efficiency while exhibiting remarkably low off-target editing and cellular toxicity. Furthermore, with a significantly smaller size compared to conventional dominant-negative MLH1 (MLH1dn), the polypeptide of the present invention can be easily integrated into various existing prime editing systems and one vector and is universally applicable. Therefore, the novel MLH1-binding polypeptide of the present invention and the nucleic acid encoding same can be advantageously used in the field of gene editing.

Disclosed is use of Raddeanoside R8 in the preparation of a DKK1 inhibitor and a cancer therapeutic drug. Raddeanoside R8 can bind to DKK1 and inhibit the activity of DKK1; moreover, Raddeanoside R8 can inhibit the viability or invasion ability of cancer cells expressing DKK1 proteins.

The present invention relates to an orally administered anti-inflammatory low-molecular-weight compound for treating inflammatory bowel disease, and use thereof. More specifically, the low-molecular-weight compound of the present invention can inhibit the activation of immune cells mediated using RAGE and TLR by targeting HMGB1 and directly binding thereto, and thus can inhibit the expression or secretion of inflammatory cytokines, enzymes and the like from immune cells, acts effectively even with respect to HMGB1 non-mediated inflammatory responses, effectively inhibits inflammatory responses in intestinal tissues when orally administered to inflammatory bowel disease animal models, and induces the regeneration of the intestinal mucosal layer by alleviating inflammatory responses, thereby being used the prevention or treatment of inflammatory bowel disease.