88 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.

A composition is orally or topically administered to a patient susceptible to infection by an orthopoxvirus such as monkeypox (mpox). The composition includes inhibitors configured to bind to orthopoxvirus envelope proteins, e.g., MPXV A29 from mpox. The inhibitors can include sulfated polysaccharides or glycans such as heparin, chondroitin sulfate A, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate C, chondroitin sulfate D, chondroitin sulfate E, pentosan polysulfate, mucopolysaccharide polysulfate, or combinations thereof. Binding of the composition to the envelope proteins inhibits the interaction between the virions and heparan sulfate proteoglycans (HSPG) and thus the ability of the virions to enter the host cell. Limiting this transport across the host cell membrane inhibits initial viral infection, as well as limits spread of that infection from cell to cell even in the event viral infection is initially achieved, providing significantly improved patient treatment and recovery outcomes relating to orthopoxvirus infections such as mpox.

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.

The invention belongs to the technical field of biomedical technology, and particularly relates to application of BTN2A2 as an immune checkpoint in preparation of an anti-tumor product. The BTN2A2 is taken as an immune checkpoint, the BTN2A2 is found to have up-regulated expression in various tumor cells (including pancreatic cancer and glioma) and APC cells, and the BTN2A2 is combined with corresponding receptors on T cells to inhibit proliferation and activation of the T cells, so that the T cells are in an inactivated state, and finally immune escape is induced. By preparing the anti-BTN2A2 monoclonal antibody, the combination of BTN2A2 and a receptor can be blocked, the growth and proliferation of T cells can be up-regulated, the recognition of the T cells on tumor cells can be enhanced, the attacking and killing functions of the T cells can be activated, and the anti-tumor effect can be achieved.

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 present invention provides an anti-RBD single-chain antibody No.35 and the use of preparing an antibody-drug conjugate, wherein the DNA sequence of the anti-RBD single-chain antibody No.35 is shown in SEQ ID No.1, and the anti-RBD single-chain antibody No.35 comprises complete heavy chain and light chain variable region sequences, and can specifically bind to RBD. The single-chain antibody No.35 is connected to the N-glycosylation inhibitor tunicamycin (TM) through glutaraldehyde, binds to the RBD region of the new coronavirus S protein, is internalized by a cell line expressing ACE2, and the release of the small molecule drug tunicamycin can inhibit the glycosylation of the S protein and ACE2, block the binding of the new coronavirus to the receptor, and inhibit the further invasion of the coronavirus into the cell, thereby affecting the infection and proliferation of the progeny virus. It can be used for the development of coronavirus-targeted therapeutic antibody drugs, especially for the preparation of antibody-drug conjugates that inhibit new coronavirus infection.

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 belongs to the technical field of biological medicine, and particularly relates to application of a miR-21 inhibitor loaded and iRGD peptide modified 293T cell exosome and a method for treating osteosarcoma cis-platinum resistance based on the modified 293T cell source exosome and combining with the miR-21 inhibitor. The miR-21 inhibitor is loaded into the exosome by using an electroporation technology, tumor cells are accurately targeted, activation of ferroptosis signal channels is promoted, the treatment effect of cis-platinum is remarkably enhanced, and the drug resistance of cis-platinum is overcome. The technology provides a novel drug delivery platform for precise treatment of osteosarcoma.

An improved assay is required to measure the immunogenicity of vaccines while overcoming some limitations of current immunogenic biomarkers. Disclosed herein is an assay for measuring inhibition of binding between a SARS-CoV-2 spike (S) glycoprotein and hACE2. Also provided herein are methods of using the assay to evaluate the efficacy of a COVID-19 vaccine.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.

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.

The invention provides an STAT3 inhibiting polypeptide, an anti-tumor drug and application, and belongs to the technical field of biological medicine. The amino acid sequence of the STAT3 inhibiting polypeptide is at least one of SEQ ID NO: 1 to SEQ ID NO: 3. According to the invention, an SH2 structural domain in a negative regulatory protein SH2 adapter protein F (Shf) of STAT3 is taken as a template, the sequence of the template is as shown in SEQ.ID NO: 4-OH, the template is combined with active fragments for splicing, a STAT3 inhibition polypeptide is designed, the STAT3 inhibition polypeptide has excellent STAT3 affinity, can be combined with highly expressed STAT3 in tumor cells and inhibit the activity of the STAT3, the high selectivity of the template to the tumor cells is retained, and the application of the STAT3 inhibition polypeptide to the tumor cells is realized. And the tumor inhibition effect is enhanced. Therefore, the STAT3 inhibiting polypeptide or the pharmaceutical salt thereof has potential anti-tumor clinical application value and wide development prospect.

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 present invention relates to the field of biomedicine, and specifically provides an application of a selective TNFR1 antagonist peptide SN61‑4G in the treatment of non-alcoholic fatty liver disease. The selective TNFR1 antagonist peptide SN61‑4G has an amino acid sequence as shown in SEQ ID NO: 1. The present invention preliminarily verified its selective binding to TNFR1 and in vitro anti-inflammatory activity through in vitro experiments. The results showed that SN61‑4G may exhibit good anti-inflammatory activity by selectively binding to TNFR1 and inhibiting the interaction between TNF‑α and TNFR1. The present invention applies it to a mouse non-alcoholic fatty liver disease model induced by a high-fat and high-sugar diet (HFD), which is of great significance for the development of therapeutic drugs for non-alcoholic fatty liver disease.

The present invention relates to an antibody specifically binding to human leukocyte antigen G (HLA-G) or an antigen-binding fragment thereof, and use thereof. The antibody specifically binding to HLA-G or an antigen-binding fragment thereof can exhibit excellent anticancer effects such as that of inhibiting tumor growth by inhibiting the interaction between HLA-G and ILT-2 while specifically binding to HLA-G.

The present invention relates to a polypeptide derived from CAP1 and a pharmaceutical composition comprising the same as an effective ingredient and, more particularly, to a peptide including the amino acid sequence of SEQ ID NO: 1, any 0 to 20 amino acid residues added to the N terminus thereof, and any 0 to 75 amino acid residues added to the C terminus thereof, and a pharmaceutical composition comprising the peptide as an effective ingredient for the prevention and alleviation of inflammatory diseases, the inhibition of cancer and cancer metastasis, the prevention and alleviation of diabetes, fatty hepatitis, arteriosclerosis, cardiovascular diseases, and heart failure. Exhibiting the effect of suppressing the binding of resistin to CAP1 and inhibiting NF-kB activity, the method of the present invention can be useful for treating inflammatory diseases, cancer, diabetes, fatty hepatitis, arteriosclerosis, cardiovascular diseases, and heart failure which are caused by the activation of resistin and NF-kB.