788 results about "Protein degradation" patented technology

The invention provides a KRAS G12D protein degradation agent and application thereof in medicine, and particularly provides a compound with a structure as shown in a formula (I) and application of a stereoisomer or a prodrug molecule containing the compound or pharmaceutically acceptable salt of the compound as medicine. The compound can degrade KRAS G12D protein in a targeted manner through a ubiquitin-proteasome way, so that the compound can be used for treating indications mediated by abnormal expression of the KRAS G12D protein. Wherein each group in the formula (I) is defined in the specification. # imgabs0 #

The present disclosure relates to methods of co-administering PROTAC (proteolysis targeting chimera) compounds that can promote ubiquitination and degradation of a target protein. The present disclosure also relates to antibody drug conjugates of PROTAC compounds Also disclosed herein are pharmaceutical compositions that can include a compound of Formula (V), the use and preparation thereof.

Provided herein are SOS1 protein degraders, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of an SOS1-mediated disorder, disease, or condition.

Disclosed are a compound targeting a protein modulator and a use thereof. The compound is a compound represented by formula (I), or a pharmaceutically acceptable salt thereof. The compound of the present invention has a good inhibition effect or protein degradation effect on a KRAS mutant.

A compound targeting a KRAS protein degradation agent, and a use thereof. The compound is a compound having an F-L-M structure, or a tautomer, racemate, enantiomer, or diastereomer thereof, or a mixture thereof or a pharmaceutically acceptable salt thereof, wherein F is a KRAS protein binding fragment, L is a linking unit for linking F and M, and M is a VHL binding fragment. The compound can be used for treating diseases caused by KRAS mutation or amplification.

The invention discloses a modified Trim 21 (delta Trim 21)-based target protein degradation control system, which takes a modified protein delta Trim 21 degradation system as a basis, takes blue light, abscisic acid, Danoprevir and / or MK-5172 as inductors, controls the combination of target protein and delta Trim 21 by introducing and modifying a controllable protein dimerization system on the basis of the modified protein delta Trim 21 degradation system, and improves the target protein degradation control system. The protein targeted degradation capable of being modularly regulated and controlled is carried out. Two regulation and control modules, namely a target protein recognition module and a degradation module based on E3 ubiquitinase, are constructed by splitting and recombining a controllable protein dimerization system and a delta Trim 21 structural domain. The invention also discloses a degradation device comprising the system. The invention also discloses a method for accurately regulating endogenous proteins (degradation of proteins related to tumorigenesis) by using the programmable regulation type modular protein degradation device, so as to achieve the effect of specifically killing tumors. The invention also provides a eukaryotic expression vector and a regulation method of the programmable regulation type protein targeted degradation device.

The invention provides a construction method and application of a pichia pastoris strain capable of efficiently secreting and expressing recombinant human-derived protein, and relates to the technical field of synthetic biology. According to the invention, pichia pastoris is used as a chassis strain, a ku70 gene and / or a pep4 gene in a pichia pastoris genome are / is knocked out through a gene editing technology, and a new signal peptide O factor signal is introduced, so that the secretion efficiency of the pichia pastoris for secreting and expressing recombinant human-derived protein can be remarkably improved, the problem of protein degradation is effectively improved, and the recombinant human-derived protein can be obtained. And meanwhile, a high-copy pichia pastoris strain is efficiently obtained, so that the expression quantity of recombinant human protein is improved, and powerful support is provided for research and development of related drugs and biological manufacturing.

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrade and / or otherwise modulate (e.g., inhibit) NIMA Related Kinase 7 (NEK7). Said chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having one or more disorders or diseases associated with NLRP3 inflammasome activation. Said disorders or diseases include but are not limited to, autoinflammatory and autoimmune disorders (e.g., gout, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease), cardiovascular and metabolic disorders (eg. pericarditis, atherosclerosis, Type 2 diabetes, obesity, and metabolic syndrome), fibrotic disorders (e.g. interstitial lung disease, chronic kidney disease), hematology (eg. anemia of inflammation) and eye disorders (eg. macular degeneration). In embodiments, and while not wishing to be bound by theory, it is believed that the chemical entities described herein directly target (e.g., directly bind to) NEK7, thereby altering (e.g., attenuating) the inflammatory response modulated by the NLRP3 inflammasome. This disclosure also features compositions containing the same as well as methods of using and making the same.

The present invention provides a class of small molecule compounds for targeted degradation of a pan-KRAS protein, a preparation method therefor, and use thereof as a therapeutic agent for preventing and / or treating cancer. The compound of the present invention can effectively degrade and / or inhibit the pan-KRAS protein in cells, and can be used for preparing a drug for treating and / or preventing related diseases or disorders caused by pan-KRAS mediation.

The invention provides a compound as shown in a formula (I) and a racemate, a stereoisomer, a tautomer, an isotope label, a nitrogen oxide, a solvate, a polymorphic substance, a metabolite, ester, a prodrug or pharmaceutically acceptable salt thereof, which have better BRD4 inhibition and degradation effects as a drug, and can be used for preparing drugs related to BRD4 inhibition and degradation. And preventing and / or treating related diseases. # imgabs0 #

The invention provides a recombinant XVII type collagen and application thereof, and relates to the technical field of protein engineering. The novel recombinant human XVII type collagen is obtained by optimizing and screening collagen structural domain sequences of the human XVII type collagen and then combining the sequences. The recombinant human XVII type collagen is consistent with the corresponding part of the amino acid sequence of the human XVII type collagen, does not generate immunological rejection when being applied to a human body, and can be widely applied to the industries of surgical medical treatment and medical beauty. In addition, the recombinant human XVII type collagen is high in stability, and the problem of protein degradation in the process of expressing recombinant protein by pichia pastoris can be avoided. In addition, the recombinant human XVII type collagen also has the effects of high biological activity, high biological safety, promotion of cell proliferation and differentiation and promotion of hair growth, and can be applied to the field of cosmetics or medicines as a functional component.

This patent application discloses a self-assembled recombinant collagen, a preparation method and use thereof. The amino acid sequence of the self-assembled recombinant collagen of the present invention is shown in SEQ ID No. 1, and it can self-assemble in an aqueous solution to form a heptamer structure. The self-assembled recombinant collagen has excellent long-term storage stability, effectively avoiding the problem of protein degradation during storage.

The invention discloses a cationic polymer-based proteolysis targeting chimera as well as preparation and application thereof, and belongs to the fields of targeting protein degradation and nanotechnology. According to the chimera, a cationic polymer is used as a connecting arm to connect a target protein ligand and an E3 ubiquitin ligase ligand to form a ternary complex, so that efficient degradation of target protein is realized. By adjusting the ligand proportion, chimeras with different degradation efficiencies can be synthesized, and accurate regulation and control are realized. The pH-responsive nano-drug obtained by hydrolyzing the targeting chimera by using the targeting protein can respond to an acidic tumor microenvironment, specifically release the chimera, and improve the targeting property and the treatment effect of the drug. Compared with the traditional PROTACs, the compound has higher bioavailability and tumor permeation effect; the preparation method of the nano-drug is simple and easy to implement, provides possibility for preparation of high-performance nano-drugs, shows potential in preparation of anti-tumor cell drugs, provides new thoughts and methods for tumor treatment, and has important clinical application value.

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The present disclosure relates to compounds that elicit degradation of proteins directed against the protooncogene tyrosine protein kinase receptor (RET), which may be a wild-type RET or a mutant form of RET, including compounds of formula (I), for use in the treatment of diseases and conditions mediated by said proteins. # imgabs0 #

Provided are a cyanoquinoline-targeting protein degradation molecule, a preparation method therefor and a use thereof. Particularly, the present invention relates to a compound represented by general formula (I), a preparation method therefor, a pharmaceutical composition comprising the compound, and a use of the compound as a protein degradation targeting chimera of an androgen receptor in preparation of medicaments for treating related diseases (including prostate cancer, breast cancer, and spinal and bulbar muscular atrophy) controlled by the androgen receptor, wherein the definitions of the substituents in general formula (I) are the same as those in the description.

The invention discloses an enzyme response type KRAS targeted protein degradation chimera as well as a preparation method and application thereof, and belongs to the technical field of tumor targeted therapy. The enzyme response type KRAS targeted protein degradation chimera disclosed by the invention is obtained by covalently linking three parts, namely a KRAS targeted protein degradation chimera, an enzyme response type amino acid sequence and a cell penetrating peptide amino acid sequence, wherein the KRAS targeted protein degradation chimera is obtained by linking a KRAS targeted peptide and a VHL E3 ligase ligand through succinic acid. The enzyme response type KRAS targeted protein degradation chimera releases the KRAS targeted protein degradation chimera under the action of ATG4 enzyme shearing, and shows a relatively strong lung cancer resisting effect in vitro and in vivo. The invention has significant advantages in the aspect of antitumor drugs, and opens up a new field for the development of targeted protein degradation chimera drugs. Enzyme response type KRAS targeted protein degradation chimera molecular structural formula as follows: # imgabs0 #

According to the GPX4 protein degradation agent and the application, the degradation agent serves as molecular glue to induce tumor cell ferroptosis and is different from an existing PROTAC technology, and the molecular glue can induce interaction between E3 ubiquitin ligase and target protein GPX4 and promote ubiquitination of the E3 ubiquitin ligase and the target protein GPX4. Compared with the existing GPX4 degradation agent, the molecular glue has the advantages of small molecular weight, high cell permeability and better druggability. The GPX4 molecular glue disclosed by the invention can be used for effectively degrading GPX4 and has a killing effect on various tumor cell lines. The preparation method is simple in synthesis route and mild in reaction condition, can be used for being developed into a new generation of GPX4 targeting drugs, and has great clinical application value and considerable market potential.

The invention discloses an E3 ubiquitin enzyme mutant as well as modification and a protein targeted degradation system and application thereof, and particularly relates to a series of targeted protein degradation enhanced E3 ubiquitin enzymes (Trim21-N) and a modification method thereof, the E3 ubiquitin enzymes (Trim21-N) are obtained by modifying a wild type Trim21 (wtTrim21) protein structural domain, and the E3 ubiquitin enzymes comprise Trim21-a, Trim21-b, Trim21-c, Trim21-d, Trim21-e and Trim21-f. The efficiency of degrading the target protein through the ubiquitin proteasome is remarkably improved, and the method has the characteristics of strong endogenous and exogenous universality, high specificity, ubiquitin proteasome dependence, low cytotoxicity, strong cell compatibility and the like on the degradation of the target protein. The invention provides E3 ubiquitin enzyme (Trim21-N) based on a targeted protein degradation enhancement version and an exogenous fluorescence report degradation system of the E3 ubiquitin enzyme (Trim21-N), preferably Trim21-e with the optimal degradation effect, and the E3 ubiquitin enzyme (Trim21-N) is named as delta Trim21. The invention further provides an endogenous protein degradation system based on the delta Trim21. The method has the characteristics of high specificity, rapidness and small module, so that the method can be used for researching various biological and disease mechanisms, including the fields of cell targeted therapy, cell mechanism exploration, genetic engineering and the like.

The invention provides a bifunctional compound for targeting androgen receptor protein degradation and application thereof, and belongs to the field of medicines. Specifically, the invention discloses a compound as shown in a formula I, a preparation method thereof, a pharmaceutical composition containing the compound, and application of the compound in preparation of drugs for preventing or treating androgen-mediated diseases.

The present invention relates to compounds of formula I. The compounds of the present invention are SMARCA4 protein degradation agents for the treatment of cancer. # imgabs0 #

The invention discloses a composition for treating diseases through protein degradation in a novel degradation way, and relates to the technical field of medicines. Comprising a mandolin-based androgen receptor degradation chimeric peptide (MbTACs), the mandolin-based androgen receptor degradation chimeric peptide (MbTACs) contains a targeting module YLCSSNNRERDKFRR combined with AR and a module combined with midnolin, a KLVFF sequence and a cell penetrating peptide PKKKPKV are added to the C end of the peptide, and a polypeptide molecule MbAD is formed. According to the invention, a midnolin-based MbTACs platform is developed, and the midnolin-based MbTACs platform is used for degrading specific proteins. The bifunctional molecules form a midnolin-MbTACs-target protein ternary complex between the target protein and the midnolin, and then the protein is degraded through a midnolin-proteasome way. The MbTACs can effectively degrade c-Myc and androgen antibodies in vitro and in vivo, and play an anti-tumor role. The MbTACs molecule represents a first midnolin-based target chimera, and the MbTACs molecule represents a first midnolin-based target chimera.

The invention discloses a PARP1 selective protein degradation agent and an application of the PARP1 selective protein degradation agent in tumor resistance. The degradation agent has the following structural formula. Wherein the 3-ethyl-7-((4-(pyridine-3-yl) piperazine-1-yl) methyl) quinoxaline-2 (1H)-ketone part is a PARP1 target protein ligand, and L is a connecting unit; and B is an E3 ubiquitin ligase ligand. The PARP1 selective protein degradation agent prepared by the preparation method disclosed by the invention can be used for effectively degrading PARP1 protein, inhibiting cell proliferation and inducing tumor cell apoptosis. Meanwhile, when the compound is combined with chemotherapeutic drugs, the effect of enhancing the chemotherapeutic effect is achieved, almost no physiological toxicity exists, and the compound is expected to provide an ideal way for improving treatment of various diseases caused by PARP1 excessive activation. # imgabs0 #

The invention belongs to the field of food processing, and particularly relates to an ostrich meat preservative and a preservation method. The ostrich meat preservative provided by the invention is prepared by matching and mixing the chitosan, the nisin and the tea polyphenol according to a specific proportion, so that the refrigeration refreshing time of the ostrich meat treated by the preservative can be effectively prolonged, the ostrich meat can maintain a relatively high L * value and a * value within 16 days of storage, the deterioration of meat color is delayed, the water-retaining property is remarkably improved, and the quality of the ostrich meat is improved. The content of thiobarbituric acid reactants and volatile basic nitrogen is obviously reduced, and fat oxidation and protein degradation are inhibited; the total number of bacterial colonies and the number of microorganisms such as coliform bacteria, pseudomonas, mould and saccharomycetes are obviously reduced. The growth and reproduction of putrefying bacteria can be effectively inhibited, and the cold fresh shelf life is prolonged.

The invention discloses a covalent lysosome targeting chimera based on a nucleic acid aptamer and application of the covalent lysosome targeting chimera in protein degradation and immunotherapy, and belongs to the technical field of biology. The invention designs a covalent lysosome targeting chimera with click chemical reaction activity, and the simple and efficient covalent lysosome targeting chimera is used for realizing efficient protein degradation at the levels of cells and living bodies. When the tool is used for targeted degradation of immunotherapy biomarkers, immunogenic apoptosis of tumor cells can be caused, so that killing of an immune system to tumors is more efficiently activated. Meanwhile, the covalent lysosome targeting chimera overcomes the problem of immune-related side effects confronted by existing antibodies and polysaccharide peptide drugs, and can effectively avoid the potential occurrence risk of the immune-related side effects while efficiently degrading the target protein.

Targeting liposomes for protein degrader delivery. In one embodiments, the targeting liposome including a phospholipid, a cholesterol or cholesterol derivative, a PEG lipid, a targeting lipid; and a protein degrader. In other embodiments, the targeting liposome including a phospholipid, a cholesterol or cholesterol derivative, a PEG lipid, a targeting lipid; and a protein degrader- ligase complex. Also provided are kits for preparing targeting liposomes for protein degrader and / or protein degrader-ligase complexes. Also provided are methods for preparing such targeting liposomes.

The invention belongs to the technical field of medicines, and particularly relates to a protein degradation targeting chimera and application thereof. The protein degradation targeting chimera has a structure as shown in a formula (I), and the definition of each group in the formula is shown in the specification. The compound shown in the formula (I) has better inhibitory activity on CDK2. # imgabs0 #

The invention provides an NSD protein degradation agent and application thereof, and particularly provides a compound with a structure as shown in a formula (I) or pharmaceutically acceptable salt thereof, or a stereoisomer or a prodrug molecule thereof. The compound can degrade proteins such as NSD2, NSD1, NSD3, c-MYC, KLK3 / PSA, AR, NKX3.1, GSPT1 and the like in a targeted ubiquitination manner, so that the compound can be used for treating indications related to abnormal expression of the proteins such as NSD2, NSD1, NSD3, c-MYC, KLK3 / PSA, AR, NKX3.1, GSPT1 and the like. # imgabs0 #

This disclosure provides compounds of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)), or pharmaceutically acceptable salts thereof, that induce degradation of a BCL6 protein. These compounds are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same

The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.