10 results about "BRAF Protein" patented technology

The present invention provides compounds or their pharmaceutically acceptable salts and their pharmaceutical compositions that can be administered to a host such as a human in need thereof for the treatment of a disorder, such as cancer, mediated by mutant BRAF. The compounds efficiently degrade Class I, II and III mutant BRAF proteins.

The invention relates to the technical field of biological medicines, and provides a polypeptide targeting a BRAF dimer and an application of the polypeptide in tumor resistance, the polypeptide takes a straight-chain peptide TRHVNILLFM-OH as a peptide chain template, the straight-chain peptide is constructed through specific amino acid replacement, the C terminal is gradually truncated and cyclized to construct a cyclic peptide, and a specific sequence is coupled to develop a composite peptide strategy for modification, so that the polypeptide targeting the BRAF dimer is obtained. The cyclic peptide CBF-2, the cyclic peptide CBF-2-2 and the cyclic peptide SCBF-2-2 are obtained. Experiments prove that the polypeptide can effectively inhibit proliferation and invasion of tumor cells; the serum protein has high stability and excellent cell penetrating capability, and can penetrate through a cell membrane to enter cytoplasm, so that target protein in cells can be better targeted to exert biological functions of the target protein. Therefore, the multi-functional composite peptide can be developed through a polypeptide modification strategy, the membrane permeability and the stability of the multi-functional composite peptide are improved, the binding force of the multi-functional composite peptide and the BRAF protein is further improved, and the effects of inhibiting proliferation of tumor cells and resisting invasion are achieved at the same time.

The present invention provides compounds or their pharmaceutically acceptable salts and their pharmaceutical compositions that can be administered to a host such as a human in need thereof for the treatment of a disorder, such as cancer, mediated by mutant BRAF. The compounds efficiently degrade Class I, II and III mutant BRAF proteins.

The invention provides a bicyclic heteroaryl BRAF negative allosteric modulator and a preparation method and application thereof.The structural general formula of the bicyclic heteroaryl BRAF negative allosteric modulator or pharmaceutically acceptable salt of the bicyclic heteroaryl BRAF negative allosteric modulator is shown as I. The bicyclic heteroaryl BRAF negative allosteric modulator targeting BRAF kinase is high in effect and good in druggability and can be used for preparing BRAF kinase. The drug resistance phenomenon caused by BRAF protein dimerization is overcome. A test example verifies that the compound synthesized by the invention shows remarkable cell proliferation inhibition activity on BRAFWT, BRAFV600E and a p61-BRAFV600E tumor drug-resistant cell line constructed by slow virus transient transfer, has remarkable kinase inhibition activity, and has a good application prospect; and # imgabs0 # I is adopted.

This invention provides compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which can be applied to a host in need, such as humans, to treat conditions mediated by mutant BRAF, such as cancer. These compounds effectively degrade class I, II, and III mutant BRAF proteins.

The present invention provides compounds or their pharmaceutically acceptable salts and their pharmaceutical compositions that can be administered to a host such as a human in need thereof for the treatment of a disorder, such as cancer, mediated by mutant BRAF. The compounds efficiently degrade Class I, II and III mutant BRAF proteins.

The invention discloses a polymer composition and application thereof in preparation of a medicine taking a Braf protein degradation agent as an active component. The polymer composition is prepared from the following raw materials: fucoidan, hydroxyethyl cellulose and polyvinyl alcohol, according to the high-molecular composition, fucoidan, hydroxyethyl cellulose and polyvinyl alcohol with different molecular weights are adopted, a cross-linked network structure is formed through the strong hydrogen-bond interaction among molecules, the good slow-release effect on the Braf protein degradation agent is achieved, and the stability of the Braf protein degradation agent can be effectively improved; in addition, the invention also provides a pharmaceutical composition, and the pharmaceutical composition has good inhibitory activity on SK-MEL-28 human melanoma cells, has a good degradation effect on Braf protein in the SK-MEL-28 human melanoma cells, and has a good potential treatment effect on solid tumors such as melanoma.

The present invention provides bicyclic heteroaryl BRAF negative allosteric modulators, their preparation methods and uses. The general structural formula of the bicyclic heteroaryl BRAF negative allosteric modulators or their pharmaceutically acceptable salts is shown as Ⅰ. The present invention synthesizes bicyclic heteroaryl BRAF negative allosteric modulators that are potent and have good drug-likeness and target the BRAF kinase, overcoming the drug resistance phenomenon caused by BRAF protein dimerization. Verified by test examples, the compounds synthesized by the present invention have significant cell proliferation inhibitory activity against BRAF WT , BRAF V600E and the p61-BRAF V600E tumor drug-resistant cell lines constructed by lentivirus transient transfection, and at the same time have significant kinase inhibitory activity, showing good application prospects; Ⅰ.

The invention discloses a protein function prediction method based on a graph neural network and a GO term hierarchical relationship and a related device. The method comprises the following steps: obtaining protein sequence data, protein PPI data corresponding to the protein sequence data and protein GO term data corresponding to the protein sequence data; performing feature extraction processing based on the protein sequence data and the protein PPI data to obtain a protein feature vector; performing term feature extraction processing based on protein GO term data corresponding to the protein sequence data to obtain a term feature vector corresponding to each piece of protein GO term data; and mapping the protein feature vector and the term feature vector corresponding to each piece of protein GO term data into the same semantic space, and performing protein function prediction processing in the semantic space. In the embodiment of the invention, better protein prediction performance is achieved, and compared with a traditional prediction method, the performance is greatly improved.

The invention relates to a protein degradation targeting chimera compound with degradation and / or inhibition activity on mutant BRAF, and also relates to a pharmaceutical composition containing the protein degradation targeting chimera compound, and a preparation method and application of the protein degradation targeting chimera compound.