178 results about "De ubiquitination" patented technology

The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

The invention discloses a universal construction method for a protein-targeting chimeric molecule compound. The objective of the invention is to provide a method for adjusting the level of proteins by degrading the proteins through targeted ubiquitination. The construction method mainly comprises the following steps: 1) locating and analyzing a three-dimensional structure of a target protein and predicting active sites; 2) selecting a compound database; 3) virtually screening ligand compounds having high degrees of adaption to the target protein by using a computer; 4) acquiring the screened ligand compounds and screening an optimal ligand compound of the target protein through detection of interaction between micromolecules and the proteins; 5) constructing a protein-targeting chimeric molecule compound composed of the optimal ligand compound of the target protein, ubiquitin ligase E3 identification ligand and Linker connecting the optimal ligand compound of the target protein to the ubiquitin ligase E3 identification ligand by using a combination manner simulated by the computer; and 6) chemically synthesizing the protein-targeting chimeric molecule compound. With the method provided by the invention, the protein-targeting chimeric molecule compound can be rapidly and highly efficiently prepared, and specific degradation of intracellular target proteins is realized.

This invention describes compounds and pharmaceutical compositions useful as ubiquitin agent inhibitors, particularly ubiquitin ligase inhibitors. The compounds and pharmaceutical compositions of the invention are useful as inhibitors of the biochemical pathways of organisms in which ubiquitination is involved, such as signal transduction pathways. The invention also comprises the use of the compounds and pharmaceutical compositions of the invention for the treatment of conditions that require inhibition of ubiquitination. Furthermore, the invention comprises methods of inhibiting ubiquitination in a cell comprising contacting a cell in which inhibition of ubiquitination is desired with a compound or pharmaceutical composition according to the invention. Particularly, the compounds and pharmaceutical compositions are useful to inhibit the ubiquitin ligase activity of MDM2.

The invention discloses a compound based on CRBN ligand inducing EGFR degradation as shown in the following formula I or a pharmacologically acceptable salt and hydrate. The invention further discloses a preparation method of the compound and a pharmaceutical composition of the compound, and application of the compound and the pharmaceutical composition to preparation of drugs for prevention or/and treatment of a cancer. The compound can carry out ubiquitination labeling on the EGFR, protein degradation can be induced with only less dosage, the process is similar to a catalytic reaction, drugswith same molar weight do not need, and the toxic and side effect on a human body can be reduced; and the excellent EGFR protein degradation effect and anticancer activity can be further shown, the anticancer effect of the compound is better than that of an EGFR inhibitor, the compound can be used for preventing or/and treating a variety of cancers, and has a great application prospect in the field of healing drugs.

The present invention relates to an isolated chimeric molecule comprising a degradation domain including a eukaryotic U-box motif and a targeting domain capable of immuno specifically directing the degradation domain to a substrate where the targeting domain is heterologous to the degradation domain. A linker couples the degradation domain to the targeting domain. Also disclosed are compositions as well as methods of treating a disease, substrate silencing, screening agents for therapeutic efficacy against a disease, and methods of screening for disease biomarkers.

The invention discloses small molecule degradation agents targeting at androgen receptors, belongs to the field of biological medicines, and particularly relates to a series of compounds for degradingandrogen receptor proteins in a targeted ubiquitination manner, a synthesis method and medical applications of the compounds, in particular in prevention or treatment of androgen receptor related diseases. Meanwhile, a series of in-vitro anti-tumor activity evaluation tests are carried out on the synthesized compounds by invertors of the invention, and the compounds have certain inhibitory activity on cancer cells.

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to the use of DUB or desumoylating inhibitors in the treatment of cancer. Described herein are compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R^1a, R^1b, R^1c and R^1d each independently represent hydrogen, optionally substituted C₁-C₆ alkyl or R^1a and R^1b together form an optionally substituted C₃-C₆ cycloalkyl ring, or R^1c and R^1d together form an optionally substituted C₃-C₆ cycloalkyl ring; A is a 5 membered nitrogen-containing aromatic ring and is substituted with at least one optionally substituted 5 to 10 membered monocyclic or bicyclic heteroaryl or aryl ring attached through an optional linker.

There is provided antibodies, epitopes and methods for detecting ubiquitinated polypeptides and ubiquitination sites in proteins. The antibodies recognize a fragment of ubiquitin that is created after samples are treated with the proteoloytical enzyme LysC (or LysN).

The invention relates to an ubiquitin E1 inhibitor and a preparation method thereof. Series compound Y-1-benzene pyrazole silane-3,5-diketone and relevant derivative (such as 4-(4-ethyoxyl-3-methoxybenzylidene)-1-benzene pyrazole silane-3,5-diketone, and the like) with different alternative groups are prepared by a liquid-phase organic synthesis method according to the structure of PRY-41(4(4-(5-nitro-furan group-methylene]-3,5-dioxo-pyrazolidine-1-radical)-ethyl benzoate). The ubiquitin E1 inhibitor can be used for inhibiting protein degradation mediated by ubiquitination and nondegradation of ubiquitination, and can kill transformed cells containing p53 in the process of blocking up the NFkB activity by the inhibitor, that is to say, the inhibitor possibly has the potential property of treating tumor and can be used as an important tool for researching ubiquitin proteinase system mechanism.

The invention relates to a proteolytic targeting chimera, and a preparation method and application thereof. The structure of the proteolytic targeting chimera is as in the description, wherein L is aconnecting group containing at least one heteroatom of N and O, and can be used to connect a pseudolaric acid part capable of being specifically combined with a target CD147 protein and a thalidomidepart capable of being connected with E3 ubiquitin ligase. Through simultaneous action on the target protein and the E3 ubiquitin ligase, activated ubiquitin is transferred to the target protein, so that selective ubiquitination on the target protein is realized, and finally the ubiquitinated target protein is recognized and degraded by a proteasome. The preparation method of the compound is simpleand is easy to realize, and the proteolytic targeting chimera can obviously reduce the level of the CD147 protein, and has high application value in preparation of medicaments for treating or preventing cancers, in particular in preparation of antitumor medicaments taking CD147 as a target point.

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

The invention discloses anti-tumor ubiquitinated protein which is mainly extracted from the following steps: (1) culture of tumor cells: resuscitating cryopreserved tumor cells and culturing the tumor cells according to a conventional culture method; (2) treatment of the tumor cells; and (3) extraction of the ubiquitinated protein. The invention further discloses an extraction method of the anti-tumor ubiquitinated protein as well as application of the anti-tumor ubiquitinated protein in preparing tumor therapeutic vaccines. Compared to the prior art, the protein disclosed by the invention can be used for greatly improving the effect of cross-immuno reaction and improving the inhibitory effect on different types of tumors to a great extent; in addition, the problem that ubiquitinated short-lived protein is fast to degrade is further overcome, and a lot of ubiquitinated protein can be quickly obtained. Finally, the asymmetry between the short-lived protein and the long-lived protein is overcome, the target spots for inducing specific effector cells are increased, and the defect that the anti-tumor vaccines are poor in anti-tumor effect based on the long-lived protein is remedied.

The present invention belongs to the field of virus immunology and particularly relates to new applications of Lpro protein and applications of an FMDV L gene deletion mutant strain. The present invention finds that the Lpro hinders JAK-STAT signal transduction in a dose-dependent manner. At the same time, a new function of the Lpro is discovered, i.e., intracellular components of a JAK-STAT pathway in cells are degraded in a lysosome-dependent manner through interaction with a specific region of STATs, rather than acting on the JAK-STAT signal transduction through classical protease activityof the Lpro. A protease activity center site of the Lpro of the FMDV is a key site participating in a lysosome degradation pathway. A protease activity center site of the Lpro is a key site of K48 ubiquitination of the Lpro. The new applications of the Lpro protein and the applications of the FMDV L gene deletion mutant strain provide new targets and theoretical supports for prevention and controland vaccine design of viruses of RNA viridae, such as viruses of foot-and-mouth diseases.

The present invention discloses application of Pt (1-oxidopyridin-2-thione) 2 in the manufacture of anti-tumor medicament, and application of Pt (1-oxidopyridine-2-thione)2 as a de-ubiquitination enzyme inhibitor in the manufacture of medicaments for control of inflammation, tissue ischemia-reperfusion injury and myocardial hypertrophy. The invention provides the medicaments with Pt (1-oxidopyridine-2-thione) 2 as an active ingredient for the control of inflammation, tissue ischemia-reperfusion injury and myocardial hypertrophy and provides more clinic choices.