379 results about "Arrestin" patented technology

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The invention discloses application of amantadine in inhibition of ITGAV in preparation of medicines for treating dry age-related macular degeneration, and belongs to the technical field of biological medicines. At present, no report for researching the ITGAV gene in the dry AMD exists, the specific action mechanism is not clear, and amantadine adaptation diseases do not include the dry AMD; according to the application disclosed by the invention, the gene target ITGAV is screened from mutual hair generation of microglial cells and RPE cells in a retina microenvironment, and amantadine is used for inhibiting ITGAV protein to relieve the progress of AMD, so that a new thought is provided for treating dry AMD. Experiments show that amantadine can inhibit ITGAV and delay EMT transformation of RPE cells. In a dry AMD mouse model induced by sodium iodate, RPE cell damage can be remarkably relieved by intraocular injection of amantadine, and the structure and function of a retina layer are improved. These results indicate that it may function in early intervention of dry AMD.

Provided in the present application are a composition and method useful for reducing the gene expression of LPA(Apo(a)) and for treating LPA-related diseases and conditions. Further provided are an LPA dsRNA agent, an LPA antisense polynucleotide agent, a composition comprising the LPA dsRNA agent and a composition comprising the LPA antisense polynucleotide agent, which are useful for reducing the expression of LPA in a cell and a subject.

Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Provided are a c-Myc protein inhibitor, and a preparation method therefor and use thereof. The c-Myc protein inhibitor selectively inhibits c-Myc protein. Therefore, the inhibitor can be used for prevention and treatment of diseases related to c-Myc protein disorders, such as cancers, cardiovascular and cerebrovascular diseases, diseases related to virus infection.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The application belongs to the technical field of biotechnology and gene therapy, and particularly relates to application of SNIP1 protein as a target in preparation or screening of an antitumor drug. The application finds that the SNIP1 protein is a non-histone substrate of lysine methyltransferase KMT5A, which promotes breast cancer cell growth, invasion and lung metastasis through KMT5A-mediated K301 monomethylation; therefore, the SNIP1 protein can be used as a target for screening of an antitumor drug, and a drug obtained by screening and inhibiting methylation of the K301 site of the SNIP1 protein can be used for antitumor; and the application provides a polypeptide specifically combined with the K301 site of the SNIP1 protein, the polypeptide is combined with the K301 site of the SNIP1 protein, inhibits methylation of the SNIP1 protein, and finally can inhibit tumor growth, proliferation, invasion and metastasis, and can be used as a new targeted antitumor drug.

The invention belongs to the field of biological medicine, particularly relates to application of a reagent for inhibiting IDO1 protein expression quantity in preparation of a medicine for preventing and treating calcified aortic valve diseases, discovers that mouse aortic valve calcification can be inhibited by knocking out IDO1 genes, and further provides a method for preventing and treating aortic valve calcification by inhibiting IDO1 protein expression level. And a new non-surgical treatment scheme is provided for prevention and treatment of calcified aortic valve diseases.

The invention relates to compounds of formula (I) which are inhibitors of MKK4 (mitogen-activated protein kinase kinase 4) and their use in promoting liver regeneration or reducing or preventing hepatocyte death. The compounds selectively inhibit protein kinase MKK4 over protein kinases JNK1 and MKK7. In formula (I), especially, Rw is —NR10SO2R12; either a) Rx and Ry are F and Rz and Rzz are H; or b) Rx, Ry and Rzz are independently halogen and Rz is H; R5 is substituted phenyl or pyrimidinyl.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The invention discloses application of an NR1D1 protein phosphorylation site in preparation of cerebral hemorrhage treatment drugs, and belongs to the technical field of molecular biology. According to the invention, the specific phosphorylation site and phosphorylation modification level of the NR1D1 protein are determined for the first time, and the NR1D1 protein can be used as a key marker for evaluating the secondary nerve injury degree of the hemorrhagic cerebral apoplexy and developing treatment and / or alleviation of the hemorrhagic cerebral apoplexy; a specific antigen peptide and an antibody for accurately detecting the NR1D1 protein phosphorylation site are further constructed, and an efficient tool is provided for molecular evaluation of hemorrhagic stroke secondary nerve injury; meanwhile, polypeptide molecules capable of inhibiting NR1D1 protein phosphorylation are researched and developed, through the dual effects of specifically blocking the phosphorylation process and reducing protein degradation, necrosis of brain tissues around hematoma after hemorrhagic cerebral apoplexy is relieved, secondary dyskinesia is improved, and the effect of inhibiting NR1D1 protein phosphorylation is achieved. And a brand new scheme is provided for molecular evaluation and targeted intervention of hemorrhagic stroke secondary nerve injury.

The invention discloses an (E)-6-(4-carbonyl phenyl) hex-2-ene-1-ketone compound as well as a preparation method and application thereof, the compound can be used as a palmitoyl transferase inhibitor, and the palmitoylation process of substrate protein is further inhibited by inhibiting DHHC protein, so that the inhibition effect on tumor cells is achieved. Embodiments show that the compounds have different degrees of anti-proliferative activity to different cancer cells and different degrees of enzyme inhibitory activity to DHHC proteins, and part of the compounds have better inhibitory activity to cancer cells and DHHC proteins than positive control drugs, and can be further developed into a new generation of antitumor drugs.

This disclosure provides compounds of Formula ( AA ) Formula ( A ), Formula ( I ) (e.g., Formula ( I-a1 )), Formula ( II ) (e.g., Formula ( II-1 ), ( II-a ), ( II-a1 ), ( II-a2 ), or ( II-a3 )), Formula ( III ) (e.g., Formula ( III-1 )), Formula ( IV ) (e.g., Formula ( IV-a ), ( IV-a1 ), ( IV-b ), ( IV-b1 ), or ( IV-c )), or Formula ( B ) (e.g., Formula ( B-1 )), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein. In some embodiments, the KRas protein has a dysregulation (e.g., the KRas protein is mutated or amplified). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) KRas activation, for example, KRas activation associated with a mutant KRas protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds as disclosed herein, or pharmaceutically acceptable salts thereof, and methods of using and making the same.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The invention belongs to the field of medicines, and discloses an SERPINE1 protein degradation agent and application thereof. The general formula of the SERPINE1 protein degradation agent is # imgabs0 # or # imgabs1 #. The research finds that a structural fragment for inhibiting SERPINE1 protein and a structural sheet or a hydrophobic label of an E3 protein ligand are coupled together through a linker, the length of the linker is adjusted, the obtained SERPINE1 protein degradation agent has an unexpected anti-tumor effect, the anti-tumor effect of the SERPINE1 protein degradation agent is superior to that of a single SERPINE1 inhibitor, and the SERPINE1 protein degradation agent has a good application prospect. The drug resistance of tumor cells can be overcome, and the drug-forming target property is good.

The invention discloses application of a small molecular compound secalonic acid B in inhibiting Skp2 protein and resisting prostate cancer cell metastasis, and belongs to the technical field of medicines. The research finds that secalonic acid B can obviously reduce the half-life period of Skp2, accelerate the degradation speed of Skp2 and reduce the protein level of Skp2 in DU145 cells by enhancing the polyubiquitination process on Skp2 protein. The secalonic acid B induces proteasome degradation of Skp2 through a multi-ubiquitination pathway of a K48 chain, so that tumor cell metastasis is inhibited, and the effect of resisting prostatic cancer is achieved. The invention discloses an action mechanism of secalonic acid B in inhibiting Skp2 protein and resisting prostate cancer cell metastasis, lays a theoretical foundation for research and development of drugs for inhibiting Skp2 protein and treating prostate cancer, and provides a new strategy for treatment of prostate cancer.

The invention discloses an antibody specifically bound with novel coronavirus nucleocapsid protein or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises a CDR1 of which the amino acid sequence is shown as SEQ ID NO: 5, a CDR2 of which the amino acid sequence is shown as SEQ ID NO: 6 and a CDR3 of which the amino acid sequence is shown as SEQ ID NO: 7; the light chain variable region comprises CDR1 of which the amino acid sequence is as shown in SEQ ID NO: 8, CDR2 of which the amino acid sequence is as shown in SEQ ID NO: 9 and CDR3 of which the amino acid sequence is as shown in SEQ ID NO: 10. The antibody provided by the scheme of the invention can specifically recognize the novel coronavirus nucleocapsid protein, and has the capability of inhibiting SARS-CoV-2 N protein from inducing excessive complement activation.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present invention provides a pharmaceutical composition for inhibiting the expression of the NFKBIZ gene and its application, belonging to the technical field of biomedicine. The present invention designs double-stranded nucleic acid molecules capable of targeting and regulating the expression of the NFKBIZ gene. By verifying the gene regulation efficiency of the nucleic acid molecules, multiple nucleic acid molecules are screened to be able to inhibit the expression of the NFKBIZ gene, and the purpose of efficiently inhibiting the expression of IκB-ζ protein is achieved at the protein level. At the same time, the present invention verifies the application of the pharmaceutical composition formed by coupling the above nucleic acid molecules and targeting ligand molecules in ophthalmic diseases. This pharmaceutical composition can solve the problems of low delivery efficiency and poor therapeutic effect of existing small molecule immunomodulatory drugs, endow small nucleic acid drugs with tissue-targeted delivery function, and has advantages such as long drug effect time and small side effects; in addition, the composition of the pharmaceutical composition is simple and easy to synthesize, and has good prospects for translational application.

To provide a composition for preventing, ameliorating or treating a disease caused by protein nitration comprising a peptide with terminal tyrosine as an effective component.SOLUTION: A peptide with terminal tyrosine has an excellent effect of inhibiting protein nitration and also an excellent effect of preventing, ameliorating or treating disease symptoms in chronic immobilization stress-induced depression / cognitive impairment model, Alzheimer's disease model, epileptic seizure model, stroke model, type 2 diabetes model, acute renal failure model, or hyperammonemia model.SELECTED DRAWING: None

The invention discloses a high-throughput screening method of an inhibitor targeting E6AP-E6 protein-protein interaction. The high-throughput screening method comprises the following steps: (1) incubating a solution of a compound to be detected with E6AP protein or E6 protein in vitro; (2) after incubation is completed, correspondingly adding E6 protein or E6AP protein into the mixed solution, uniformly mixing and then incubating; (3) after the incubation is completed, adding a fluorescence donor and a fluorescence receptor into the mixed solution, uniformly mixing and then incubating; and (4) after incubation is finished, detecting a fluorescence signal of the solution, and judging whether the compound to be detected can inhibit E6AP-E6 protein-protein interaction or not. The screening method has the advantages of convenience, rapidness, stability, high efficiency, low false positive rate, sample saving and the like.

The invention relates to a preparation method and application of a novel CDK12 / 13 covalent inhibitor substituted by a fused ring structure or a pharmaceutical composition of the novel CDK12 / 13 covalent inhibitor. The novel CDK12 / 13 covalent inhibitor with the substituted ring-fused structure has a structure as shown in a formula (I), can be used as a protein kinase inhibitor, can effectively and highly selectively inhibit the activity of CDK12 / 13 protein kinase, and can inhibit proliferation, migration and invasion of various tumor cells. # imgabs0 #