269 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.

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 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 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 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 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.

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 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.

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 present invention discloses a small molecule compound having a substituted phenylspiro[indoline-3,3'-pyrrolidine] structure, the structure of which is shown in General Formula I, and the definitions of each substituent as described in the specification and claims. The compound of the present invention can inhibit the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins. As a small molecule inhibitor of the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins, it is used in the preparation of a drug for preventing and / or treating diseases related to MDM2 and MDMX, particularly tumors.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The present invention relates to carbamate compounds of formula (I), as further detailed herein, for use in inhibiting the SARM1 protein, as well as compositions comprising these compounds and methods of treatment by administration of the compounds and compositions.

The present invention discloses an aromatic amine compound and its application. The aromatic amine compound can effectively inhibit the tyrosine kinase activity of Abelson protein (ABL1), Abelson-associated protein (ABL2) and related chimeric proteins, especially BCR-ABL1. The aromatic amine compound can be used to prepare inhibitors of Abelson protein (ABL1), Abelson-associated protein (ABL2) and related chimeric proteins, and can be used as a drug for treating diseases related to abnormal activity of BCR-ABL1 fusion protein.

To provide cross-species anti-latent TGF-β 1 antibodies which inhibit a protease mediated activation of latent TGF-β 1 without inhibiting integrin mediated activation of latent TGF-β 1.SOLUTION: To obtain the anti-latent TGF-β 1 antibodies of the present invention, anti-latent TGF-β 1 antibodies which inhibit a protease mediated activation of latent TGF-β 1 without inhibiting integrin mediated activation of latent TGF-β 1 are screened, and then humanized, and further optimized. The invention also provides combination therapies comprising an anti-latent TGF-β 1 antibody and one or more immune checkpoint inhibitors, preferably PD-1 axis binding antagonists.SELECTED DRAWING: None

The invention belongs to the technical field of biological medicine, and relates to a small molecule compound for targeted inhibition of STRAP protein and application of the small molecule compound in colorectal cancer treatment. The invention discovers that the compound Y502-6036 can inhibit STRAP protein expression or / and function for the first time; moreover, it is found through cellular level experiment research that the compound Y502-6036 can inhibit proliferation, migration or / and invasion of colorectal cancer cells, and also can inhibit tumor globular formation ability; in-vivo experimental research finds that the compound Y502-6036 can inhibit the growth of colorectal cancer tumors, so that the compound Y502-6036 can be used for preparing medicines for preventing, relieving or / and treating colorectal cancer. Besides, the compound Y502-6036 and the anti-PD-1 antibody are combined for administration, so that the synergistic interaction effect is achieved, and the inhibition effect on the colorectal cancer is remarkably improved.

The invention discloses application of a substance for inhibiting MED10 protein activity and / or expression quantity in treatment of liver cancer. Experiments prove that the expression quantity of the MED10 protein and the encoding gene thereof in liver tissues or plasma of liver cancer patients is obviously higher than that of healthy people; by inhibiting the activity and / or expression quantity of the MED10 protein, proliferation of liver cancer cells can be inhibited, growth of the liver cancer cells can be inhibited, apoptosis of the liver cancer cells can be promoted, diffusion of the liver cancer cells can be inhibited, and metastasis of the liver cancer cells can be inhibited, so that the liver cancer can be treated. The method has an important application value.

Respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are commonly treated with β2-adrenergic receptor agonists that activate intracellular signaling pathways to induce airway relaxation. However, current therapies are limited by progressive receptor desensitization, or tachyphylaxis, largely attributed to β-arrestin recruitment. This desensitization reduces therapeutic efficacy over time and complicates long-term disease management, resulting in suboptimal outcomes for patients who rely on bronchodilators for daily symptom control. Disclosed herein are pharmaceutical compositions comprising biased agonists and their methods of use, which minimally activate recruitment of beta-arrestin2.

Disclosed are inhibitors of a protein-protein interaction between protein arginine methyltransferase 5 (PRMT5) and methylosome protein 50 (MEP50) based on isoxazolyl methoxyphenyl derivatives. Further disclosed are pharmaceutical compositions comprising PRMT5:MEP50 inhibitors and methods of inhibiting protein arginine methyltransferase 5 (PRMT5) using PRMT5.MEP50 inhibitors or pharmaceutical compositions comprising PRMT5:MEP50 inhibitors.

Provided herein is a method of decreasing a-syn levels and / or decreasing a-syn toxicity in a cell, the method comprising contacting the cell with a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor and a method of inhibiting neural degeneration, the method comprising administering to a subject in need thereof a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor.

The present invention provides a spiroheterocyclic compound, its preparation method, and application. The spiroheterocyclic compound of the present invention is shown in Formula I. This compound has inhibitory activity against RORγt, effectively inhibiting the RORγt protein receptor, thereby regulating the differentiation of Th17 cells and inhibiting the production of IL-17, thereby treating RORγt-mediated autoimmune diseases. #imgabs0#

The application provides application of PAI-1 protein in detection and treatment of NEC patients and FNEC patients. The inventor of the application, in combination with years of experience and a large amount of research screening, obtains a biomarker capable of quickly assisting in diagnosis of NEC patients and identifying FNEC patients and Non-FNEC patients, and the biomarker is PAI-1 protein. The PAI-1 protein can be used for auxiliary diagnosis of NEC patients and early screening of FNEC patients, and FNEC patients are identified in time, so that intervention measures are taken in time, and mortality is reduced. Moreover, inhibition of expression of the PAI-1 protein can effectively relieve intestinal villus injury of a NEC model animal, and significantly reduce mortality. Therefore, the PAI-1 protein can be used as a potential target for treating NEC patients, and an agent for inhibiting expression of the PAI-1 protein can be used as a potential drug for treating NEC patients.

The present invention relates to a method of determining the responsiveness of a cancer patient to treatment with a compound that inhibits a KRAS protein or a KRAS protein mutant or treatment with a compound that inhibits the interaction between MDM2 and p53, the method comprising measuring the survivin level in a first sample obtained from the patient prior to treatment with the compound, measuring the level of survivin in a second sample obtained from the patient during or after treatment with the compound, comparing the level of survivin in the second sample to the level of survivin in the first sample, and determining the level of survivin in the second sample when compared to the level of survivin in the first sample. When the survivin level in the second sample decreases, it is determined that the patient is responsive to treatment with the compound. The invention further relates to the use of survivin in compounds for determining the inhibition of KRAS protein or KRAS protein mutants, or in compounds for inhibiting the interaction between MDM2 and p53, or a pharmaceutical formulation comprising said compound that inhibits a KRAS protein or a KRAS protein mutant or said compound that inhibits an interaction between MDM2 and p53 in a method of treating cancer.