459 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.

Provided herein are compounds of Formula (IV-b), 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 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 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 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 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.

Provided herein are compounds, compositions, and methods useful for inhibiting protein tyrosine phosphatases, such as protein tyrosine phosphatase non-receptor type 2 (PTPN2) and / or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases, disorders, and conditions that respond favorably to PTPN1 or PTPN2 inhibitor treatment, such as cancer or metabolic 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 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 relates to a mutant of an RSV pre-fusion conformation F protein, the mutant comprises amino acid mutation relative to an amino acid sequence of a wild type RSV F protein, the amino acid mutation is that amino acids at positions 392 and 493 or near the 493 are substituted by C, and a disulfide bond is formed between mutated positions 392C and 493C or near the 493C. The invention also provides a related DNA (deoxyribonucleic acid) coding sequence, a recombinant plasmid, an mRNA (messenger ribonucleic acid) sequence and a corresponding RSV vaccine. By introducing disulfide bonds at proper positions and combining with cavity filling, electrostatic mutation, proline mutation and the like, the expression and stability of the F protein with conformations before and after fusion and trimerization conformations are remarkably improved, and the F protein is remarkably inhibited from being converted into conformations after fusion. The mutant is also applied to preparation of RSV vaccines and detection of respiratory syncytial virus infection.

The invention discloses an NF (nuclear factor)-kappa B inhibitor. The NF-kappa B inhibitor comprises N-trans-p-coumaroyl tyramine; the invention further discloses a preparation method of the NF-kappa B inhibitor. The invention also discloses an application of the NF-kappa B inhibitor in medicines for preventing or treating diseases related to body inflammation. According to the application disclosed by the invention, the influence of the N-trans-p-coumaroyl tyramine on a TLR4 / MyD88 / NF-kappa B inflammation signal channel is detected through an immunofluorescence technology, and a result shows that the N-trans-p-coumaroyl tyramine can be used for reducing the expression of TLR4 and MyD88 proteins and inhibiting the transfer of NF-kappa B proteins to cell nucleuses, so that the N-trans-p-coumaroyl tyramine can be used as an NF-kappa B inhibitor and can be used for preparing an anti-inflammatory drug. The composition is used for preventing or treating body inflammatory response.

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 belongs to the technical field of pharmacy, and particularly relates to a method for preparing a pyridazinone compound and application of the pyridazinone compound, and the method comprises the following steps: step 1, reacting a compound as shown in a formula V with a Grignard reagent to obtain a compound as shown in a formula IV; 2, reacting the compound shown in the formula IV with succinic anhydride to obtain a compound shown in a formula III; 3, reacting the compound shown in the formula III with hydrazine hydrate to obtain a compound shown in a formula II; 4, oxidizing the compound shown in the formula II to obtain a pyridazinone compound; the pyridazinone compound or the pharmaceutically acceptable salt or prodrug of the pyridazinone compound can be used for inhibiting the activity of MET protein kinase and the mutant form of the MET protein kinase, and especially can be used as a Tepotinib intermediate.

The invention discloses an application of a sulfanyl acetamide compound with a structure shown in a formula I in preparation of a medicine for preventing and / or treating tumors and idiopathic pulmonary fibrosis. The compound can be stably combined with key amino acid residues of DDR1 protein, has a remarkable inhibition effect on phosphorylation activation of the DDR1 protein and various tumor cells, plays an anti-tumor role by effectively inhibiting protein activity, and provides an effective lead compound for subsequent drug design. # imgabs0 #

Provided is a mutant of a respiratory syncytial virus (RSV) pre-fusion conformational F protein. The mutant comprises an amino acid mutation relative to the amino acid sequence of a wild-type RSV F protein, the amino acid mutation being amino acids at a position 392 and a position 493 or a position near the position 493 being substituted by C, and a disulfide bond being formed between a position 392C and a position 493C or a position near the position 493C after the mutation. Also provided are a related DNA coding sequence, recombinant plasmid and mRNA sequence and a corresponding RSV vaccine. By introducing a disulfide bond at a suitable position, and combining same with cavity filling, electrostatic mutation, proline mutation and the like, the expression and stability of an F protein having pre- and post-fusion conformations and a trimerized conformation are significantly improved, and the conformation of the F protein is significantly inhibited from being converted into the post-fusion conformation. The mutant is also applied to preparation of an RSV vaccine and RSV infection detection.

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.

Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

The invention provides a new application of luteoloside, and luteoloside inhibits mutual combination of IGF2BP3 protein and RNA, so that protein expression of IGF2BP3 target genes c-Myc, c-Met, CDK6 and the like is reduced, cell growth is remarkably inhibited, growth of 4T1 mouse transplanted tumors is inhibited, and the luteoloside can be used as a good targeting inhibitor for treatment of IGF2BP3 high-expression tumors.

Provided herein are compounds, compositions, and methods that are useful for inhibiting protein tyrosine phosphatases, such as protein tyrosine phosphatase non-receptor type 2 (PTPN2) and / or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and that are useful for treating related diseases, disorders, or conditions, such as cancer or metabolic diseases, that respond favorably to treatment with a PTPN1 or PTPN2 inhibitor.

This invention relates to carbamate compounds of Formula (I), as further detailed herein, which are used for inhibition of SARM1 proteins, as well as compositions comprising these compounds and methods of treatment by their administration.

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.