17 results about "Druggability" patented technology

The invention relates to the field of drug discovery and delivery collaboration, in particular to an autonomous evolutionary drug discovery and delivery collaboration method and system based on a large language model. The method comprises the following steps: aiming at a given biological target three-dimensional structure, generating a candidate molecular library which is complementary with a target pocket and gives consideration to druggability through an SE (3) isovariant hybrid generation model; according to a two-stage funnel type high-throughput virtual screening process, screening out the molecule with the highest comprehensive potential from the candidate molecule library; generating a customized delivery scheme through a three-stage process; in a digital twinborn model for simulating a real in-vivo tumor microenvironment, a targeted delivery process of a drug and carrier complex is simulated, and efficiency is evaluated; atomic-scale performance confirmation is carried out on a medicine, carrier and target point ternary system through molecular dynamics simulation. The invention is suitable for drug research and development.

Disclosed are a new interleukin-2 (IL-2) mutant protein and the use thereof. Compared with wild-type IL-2, the IL-2 mutant protein has improved properties, such as an improved IL-2 receptor binding property and improved druggability. Also provided are a fusion protein, dimer and immunoconjugate comprising the IL-2 mutant protein, nucleic acids encoding the IL-2 mutant protein, the dimer and the immunoconjugate, and a vector and host cell comprising the nucleic acid. Further provided are methods for preparing the IL-2 mutant protein, the fusion protein, the dimer and the immunoconjugate, a pharmaceutical composition containing same, and the therapeutic use thereof.

This invention relates to the field of chelating drug research, specifically to chelating ligand compounds, targeted chelating ligands and their complexes and applications. Compared with the prior art, the targeted molecule linking sites and linking methods disclosed in this invention have better targeting and in vivo stability. At the same time, the design of the targeted molecule linking sites in this invention can improve in vivo metabolism and distribution, thereby improving the druggability of preferred compounds and providing a better foundation for the clinical application of therapeutic radiopharmaceuticals.

The invention belongs to the technical field of recombinant adeno-associated virus production, and discloses an rAAV production method and application. The invention provides an rAAV production method. The rAAV production method comprises the following steps: adding a cell death regulation inhibitor into a cell culture solution during rAAV production; the cell death regulation and control inhibitor is a cell apoptosis (Apoptosis) inhibitor and / or a necroptosis (Necroptosis) inhibitor. The production efficiency of the rAAV and the quality and purity of the rAAV product can be remarkably improved, the purpose of improving the quality of the rAAV product is achieved, the safety and druggability of rAAV related gene therapy products are further improved, and low-cost and large-scale production of the rAAV can be effectively promoted.

Provided in the present invention are a compound for the targeted degradation of BTK and the anti-tumor use thereof. In particular, in the present invention, a series of compounds are prepared and screened, the inhibitory and degradation activities of said compounds against Bruton's tyrosine kinase (BTK) are verified, and finally a compound with good druggability is found. The compound can be used for treating diseases associated with the activity or the expression quantity of Bruton's tyrosine kinase (BTK).

The invention relates to application of peroxidase reductase 1 as a target spot in preparation of an IS treatment medicine, and belongs to the technical field of biological medicine. The method comprises the steps of high-sensitivity blood immune proteome map construction, large-scale independent queue longitudinal correlation verification, cross-racial and multi-tissue causal correlation verification, targeted experiment verification and mechanism exploration, target druggability evaluation, treatment potential confirmation and the like, and selects immune response proteins with significant differences between patients and controls. The immune response protein strongly related to the onset risk of the cerebral arterial thrombosis (IS) is further screened from plasma, cerebrospinal fluid and brain tissue samples, and finally the cerebral arterial thrombosis traditional Chinese medicine target peroxide reductase 1 (PRDX1) is found. A drug, such as a PRDX1 agonist or overexpression PRDX1, designed aiming at the drug target can effectively improve the progress of the IS disease.

The present invention is based on the discovery of a proteolysis targeting compound having tissue targeting capability and use thereof, relating to medicinal products, and to such a compound or a pharmaceutically acceptable salt thereof, a stereoisomer, a solvate, or a polymorph. The compound is a proteolysis targeting chimera (PROTAC) with specific tissue targeting ability. The compound structure comprises three parts, i.e., A-BD-CON, wherein the part A is a PROTAC, one end of the structure thereof is a target protein ‘binding ligand, and the other end is a ubiquitin ligase ligand; and the part CON is a ligand of an asialoglycoprotein receptor (ASGPR), enabling the specific tissue targeting function. The compound enriches in liver tissue and is able to target cells in the tissue. The invention achieves improved druggability of the PROTAC with higher solubility and cellular membrane permeability, therefore produces enhanced pharmaceutical effect on the specific target tissue.

The invention relates to a virus NSP12 protein degradation agent as well as a preparation method and application thereof. Specifically, the invention relates to a compound with a structure as shown in A-L-B (formula I) or a stereoisomer or pharmaceutically acceptable salt thereof. The compound disclosed by the invention can effectively degrade coronavirus NSP12 protein and inhibit coronavirus infection, and has good druggability.

The present application provides a compound or a pharmaceutically acceptable salt, ester, or solvate thereof. The compound provided in the present application has a structure represented by the following formula (I), wherein ring A is a benzene ring or a 5- or 6-membered heteroaromatic ring. Compared with a dual-motif CAIX inhibitor XYIMSR, the compound of formula (I) or the pharmaceutically acceptable salt, ester, or solvate thereof provided in the present application has relatively strong affinity for CAIX and a relatively small molecular volume. On the basis of the small-molecule structure, when the compound is used as a carrier for a radiopharmaceutical, the obtained small-molecule radiopharmaceutical has excellent pharmacokinetic properties and druggability, thereby providing a solution for clinical application.

The invention discloses a traditional Chinese medicine prescription effective small molecule identification method fusing EGA and PPO algorithms, and relates to the technical field of traditional Chinese medicine decoction small molecule identification, and the method comprises the following steps: constructing a molecular seed bank containing TPACD known components and phytochemicals with similar structures, simulating material selection, conversion and recombination mechanisms in a traditional Chinese medicine decoction process through EGA, and identifying the effective small molecules in the traditional Chinese medicine decoction process. Three parallel modules of a basic multi-objective genetic algorithm (BMGA), an enhanced multi-objective genetic algorithm (EMGA) and an intelligent multi-objective genetic algorithm (IMGA) are established by combining sequential decision optimization capability of PPO reinforcement learning, and anti-CRC lead molecules with effectiveness, stability and druggability are screened out through molecular evolution, targeted screening, iterative refining and closed-loop feedback. The molecules generated by the invention are obviously superior to the original component of TPACD in drug-likeness, structural stability and anti-CRC activity, the IMGA module has the best comprehensive performance, and an efficient and explainable new strategy is provided for excavation of active components of traditional Chinese medicine compounds.

The invention belongs to the technical field of recombinant adeno-associated virus production, and discloses an rAAV plasmid system of a high-yield cytotoxic gene and an application of the rAAV plasmid system. The rAAV plasmid system of the high-yield cytotoxic gene comprises a transgenic plasmid, a packaging plasmid and an auxiliary plasmid, the helper plasmid comprises a gene sequence of an apoptosis inhibition factor xIAP. According to the present invention, the target auxiliary gene can be highly expressed during the production of the rAAV containing the cytotoxic gene, such that the production efficiency of the rAAV is effectively improved, and the technical effects of improving the druggability of the rAAV and reducing the production cost are achieved.

The invention belongs to the technical field of polypeptide library construction, and particularly relates to a method for constructing a thiazole polypeptide library based on a phage display technology. The method comprises the following steps: firstly, introducing a thiazole group on a polypeptide chain by using thiazole synthetase, and determining the sequence preference of the enzyme through a model peptide so as to guide library design; and integrating a gene for coding the enzyme into a host bacterium genome by utilizing CRISPR-Cas9, and constructing a stably expressed chassis cell. Carrying out PCR (Polymerase Chain Reaction) amplification on a phage vector, carrying out NotI enzyme digestion and T4 connection to construct a DNA (Deoxyribose Nucleic Acid) library, and electrically transforming the DNA library to a chassis cell to obtain a phage library for displaying the thiazole modified polypeptide. The phage display of the skeleton modified polypeptide is realized for the first time, the structural diversity of the phage display polypeptide is obviously expanded by introducing the thiazole group with unique physicochemical properties, the polypeptide stability and membrane permeability are improved, and a new technical platform is provided for screening of high-affinity polypeptide and development of druggability lead compounds.

The present invention belongs to the field of biomedicine. Provided are a bispecific antibody and the use thereof. The bispecific antibody contains a first antigen-binding domain targeting PD-L1 and a second antigen-binding domain targeting 4-1BB. The antibody retains the activity of an anti-PD-L1 antibody, achieves a balance between activity and safety, and has an excellent druggability potential.

The invention belongs to the technical field of polypeptide preparation and biological medicine, and particularly relates to a pilose antler polypeptide, a virtual enzymolysis preparation method thereof and application of the pilose antler polypeptide in the anti-aging aspect. The eight pilose antler polypeptides provided by the invention are polypeptides which are screened from pilose antler proteins and have DRP1 inhibitory activity, and have relatively high anti-aging activity and clear action mechanism; through prediction, it is found that the compound is free of toxicity and sensitization, high in DRP1 target combining capacity, good in druggability and application safety and capable of being used for developing anti-aging products, and a new lead compound is provided for research and development of new drugs, health care products or cosmetics. Furthermore, the pilose antler polypeptide is obtained based on a virtual enzymolysis preparation method, a set of complete and efficient pilose antler anti-aging peptide computer screening process is established, virtual enzymolysis, activity prediction, safety evaluation and targeted molecular docking are organically combined, the blindness of a traditional separation technology is overcome, and the separation efficiency is improved. The screening efficiency and the success rate are obviously improved.

Disclosed are compounds represented by formula (1), or their tautomers, meso compounds, racemic compounds, enantiomers, diastereomers, mixtures thereof, or pharmaceutically acceptable salts, prodrugs, or solvates thereof. The structure of formula (1) is shown below. By introducing strongly hydrophilic sulfonic acid inner salts and / or phosphate inner salt side chains at the polypeptide (VC, VA, AAA, etc.)-PAB (self-destructing group) position of the linker, the compounds significantly improve the druggability (including hydrophilicity and stability) of the antibody-drug conjugates corresponding to the compounds, reduce drug clearance in the body, and enhance tumor therapeutic effects. JPEG2026523005000202.jpg3882

The invention relates to the technical field of drugs for treating diseases related to heavy metal exposure, in particular to application of a small molecule compound of a targeted phosphorylated ARMC10 serine 43 site in preparation of drugs for treating nervous system injury caused by tin exposure. According to the technical scheme, it is found for the first time that exposure of trimethyltin chloride can specifically induce abnormal phosphorylation of ARMC10, and then neuronal death and cognitive impairment are caused. On the basis of the mechanism, a small molecule compound targeting a specific phosphorylation site of ARMC10 is provided, and by blocking mitochondrial abnormal division and dysfunction mediated by the small molecule compound, nerve injury is effectively reversed, and the structure and function of neurons are protected. The scheme solves the problem that in the prior art, due to the lack of definite drug targets, no effective therapeutic drug is provided for tin exposure related nervous system injury, and has ideal application prospects. The small molecule compound is clear in structure, clear in action mechanism and easy to carry out subsequent development, and has good druggability and commercialization prospects.

The invention relates to a 3D molecule generation method and system based on dynamic conformation guidance. The 3D molecule generation method based on dynamic conformation guidance comprises the following steps: acquiring a dynamic conformation set of protein through molecular dynamics simulation; processing the dynamic conformation set of the protein by adopting a multi-level equilateral graph attention network architecture to obtain a dynamic condition vector; a 3D molecule is generated based on an isotropic diffusion trunk and the dynamic condition vector. The dynamic conformation set of the protein is obtained through molecular dynamics simulation, after the dynamic condition vector is obtained based on the dynamic conformation set, the 3D molecule is generated based on the dynamic condition vector, it can be ensured that the generated 3D molecule not only meets the static binding requirement, but also can adapt to the real dynamic environment of the target spot, and the application prospect is wide. The problem of static-dynamic performance difference in the prior art can be effectively solved, so that the druggability of generated molecules and the success rate of experimental verification are greatly improved, and the later elimination rate of drug research and development is reduced.