67 results about "Proteasome inhibitor" patented technology

The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent).

The invention relates to an iRGD modified dual drug-loading liposome and an application of the iRGD modified dual drug-loading liposome in radiotherapy sensitization of targeted glioblastoma. The liposome is composed of HSPC, CHO-HP, DSPE-mPEG2000, and DSPE-PEG2000-MAL, and is loaded with Osimertinib (Osimertinib) and Bortezomib (Bortezomib) through a pH (Potential of Hydrogen) gradient method, and the preparation method of the liposome comprises the following steps: carrying out a reaction on the Osimertinib (Osimertinib) and the Bortezomib (Bortezomib) in the presence of a Osimertinib is used as an EGFR inhibitor, bortezomib is used as a proteasome inhibitor, and osimertinib and bortezomib synergistically enhance the radiotherapy sensitivity by weakening the DNA repair capability of tumor cells. The iRGD peptide on the surface of the liposome is combined with tumor cell specific receptors alpha v beta 3 and NRP1 in a targeting manner, so that the liposome is mediated to pass through tumor neovascularization and efficiently deliver drugs to tumor parts. Animal experiment results show that the enrichment of the liposome in tumor tissues is obviously higher than that of common liposome, and the drug release has good controllability. Compared with the prior art, the invention has obvious advantages in tumor targeting, drug delivery efficiency and radiotherapy sensitization effect, is suitable for combined treatment of radiotherapy drug-resistant glioblastoma, and has a wide clinical application prospect.

The present invention provides SETD2 protein inhibitors, as well as methods, compositions and kits for treating a disease, disorder or condition in a subject using a SETD2 protein inhibitor and optionally a second therapeutic agent, wherein the second therapeutic agent comprises one or more glycocortin receptor agonists, one or more immunomodulatory drugs, one or more proteasome inhibitors, one or more Bcl-2 inhibitors, one or more multi-effect pathway modulators, one or more XPO1 inhibitors, and one or more pharmaceutically acceptable salts thereof, one or more histone deacetylase inhibitors or one or more EZH2 inhibitors, or a combination thereof.

The invention belongs to the field of biomedical engineering, and particularly provides an application of a compound as a proteasome inhibitor, the compound is butein, the CAS number of the compound is 487-52-5, and the compound is a natural small molecule compound. Experiments prove that butein can obviously inhibit the proteasome function and is a novel proteasome inhibitor. The proteasome inhibitor screened by the invention may become a new generation of proteasome inhibitor which is better in effect, stronger in specificity, smaller in side effect and also plays a role in solid tumors; the proteasome inhibitor can be finally used for preparing drugs for inhibiting tumor cell proliferation and / or inducing tumor cell death, and has important drug and medical clinical values.

Provided herein are uses of T cells, e.g., chimeric antigen receptor (CAR) T cells, for treating a tumor or a cancer (such as B cell related cancer, e.g., multiple myeloma) wherein the subject being treated has previously received a topoisomerase inhibitor, a proteasome inhibitor, an anti-CD38 agent, an immunomodulatory agent, or an anti-SLAMF agent therapy.

The present invention provides a method of treating ALK-negative / LTK-positive cancer in a subject, comprising administering to the subject a pharmaceutically-effective dose of a linear inhibitor of ALK. The invention is of particular utility in treating multiple myeloma, including proteasome inhibitor-resistant multiple myeloma.

The present disclosure relates to methods and compositions for treating B-cell malignancies. Specifically, the present disclosure relates to a B-cell malignancy drug or composition comprising: (a) an antibody-drug conjugate (ADC) comprising an antibody or antigen-binding fragment thereof that binds to B-cell maturation antigen (BCMA) conjugated to a nucleic acid cross-linker; and (b) a proteasome inhibitor.

Provided are methods of treating a subject having a disease characterized by accumulation of FUS -associated aggregates by administering to the subject a therapeutically effective amount of a proteasome inhibitor, an agent which upregulates SAT1, or an agent which upregulates spermine, thereby treating the subject. Also provided are proteasome inhibitors, an agent which upregulates SAT1, or an agent which upregulates spermine for use in treating a subject having a disease characterized by accumulation of FUS-associated aggregates, and methods of reducing accumulation of FUS-associated aggregates in cells of a subject, the method comprising contacting the cells of the subject with a proteasome inhibitor an agent which upregulates SAT1, or an agent which upregulates spermine, thereby reducing the accumulation of FUS-associated aggregates in the cells of the subject.

The invention belongs to the field of biomedical engineering, and particularly provides application of a compound as a proteasome inhibitor, the compound is xanthohumol, the CAS number of the compound is 6754-58-1, and the compound is a natural small molecule compound. Experiments prove that xanthohumol can obviously inhibit the proteasome function and is a novel proteasome inhibitor. The proteasome inhibitor screened by the invention may become a new generation of proteasome inhibitor which is better in effect, stronger in specificity, smaller in side effect and also plays a role in solid tumors; the proteasome inhibitor can be finally used for preparing drugs for inhibiting tumor cell proliferation and / or inducing tumor cell death, and has important drug and medical clinical values.

The invention relates to application of a proteasome inhibitor in preparation of a medicine for treating tumors resistant to a tyrosine kinase inhibitor, and in the application, a plurality of strains of liver cancer cells with drug resistance to lenvatinib or regorafenib are constructed by utilizing a plurality of human liver cancer cell lines with different genetic backgrounds; a high-throughput CRISPR (clustered regularly interspaced short palindromic repeats) gene knockout screening technology and a patent medicine gene CRISPR library are utilized, and gene targets of which the gene knockout or inactivation can better kill drug-resistant cells are specifically identified from thousands of patent medicine genes. Wherein the function inactivation of a plurality of genes in the proteasome family shows more obvious cell killing activity in a plurality of drug-resistant cell models compared with non-drug-resistant cells. The invention discovers and verifies that the proteasome inhibitor has a specific killing effect on tyrosine kinase inhibitor drug-resistant liver cancer for the first time.

To provide a boronate ester compound useful as a proteasome inhibitor.SOLUTION: Provided is a compound of Formula (I) or a pharmaceutically acceptable salt thereof. (In the formula, A is 0, 1, or 2, P is hydrogen or an amino-blocking moiety, Ra, Ra1, and Ra2 are hydrogen, C1-6 aliphatic, C1-6 fluoroaliphatic, etc., and Z1 and Z2 together form a moiety derived from an α-hydroxycarboxylic acid, and in any case an atom bonded to boron is an oxygen atom, or Z1 and Z2 together form a moiety derived from a β-hydroxycarboxylic acid).SELECTED DRAWING: None

The present application belongs to the field of pharmaceutical chemistry, and specifically discloses a square amide proteasome inhibitor, a preparation method thereof and pharmaceutical application thereof.

The application discloses a kind of amide bond synthesis enzyme mutant and its application in catalyzing synthesis of drug intermediate, the mutant is P328A-T421L, and its amino acid sequence is as shown in SEQ ID NO:5.A kind of amide bond synthesis enzyme mutant in catalyzing synthesis of drug intermediate, with 2-methylthiazole-5-carboxylic acid and L-O-methyl serine as substrate, with mutant P328A-T421L or the mutant P328A shown in SEQ ID NO:3 as catalyst, drug intermediate is obtained in one step reaction, and the drug intermediate is O-methyl-N-(2-methylthiazole-5-formyl)-L-serine (MTCS).The performance of the mutant of the application compared with wild type, the performance of catalyzing synthesis of peptide epoxy ketone proteasome inhibitor oplazomib core chiral precursor MTCS is greatly improved, and conversion rate is increased from 26.8% of wild type to 76.1%.

Disclosed is a method for treating autoimmune diseases, wherein a therapeutically effective amount of a proteasome inhibitor or a pharmaceutically acceptable salt or pharmaceutical composition thereof is administered to a patient with autoimmune diseases. This method has a certain therapeutic effect on patients with autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis (LN), and autoimmune hepatitis. The proteasome inhibitor or the pharmaceutically acceptable salt or pharmaceutical composition thereof has low toxicity, thereby showing excellent clinical application prospects.

The present invention provides novel compounds useful as proteasome inhibitors. The present invention also provides pharmaceutical compositions comprising the compounds of the present invention, and methods of using the compositions to treat various diseases.

A combination comprising tasquinimod, or a pharmaceutically acceptable salt thereof, and at least one additional compound selected from a proteasome inhibitor, an immunomodulatory imide, and an antibody, for use in the treatment of multiple myeloma. A kit comprising tasquinimod and a package insert with instructions for using tasquinimod in combination with at least one additional compound selected from a proteasome inhibitor, an immunomodulatory imide, and an antibody, to treat multiple myeloma in an individual. Tasquinimod for use in the treatment of multiple myeloma, in combination with an additional compound selected from a proteasome inhibitor, an immunomodulatory imide, and an antibody.

The invention belongs to the field of biomedical engineering, and particularly provides an application of a compound as a proteasome inhibitor, the compound is lithospermum furan A, the CAS number of the compound is 85022-66-8, and the compound is a natural small molecule compound. Experiments prove that the lithospermum furan A can obviously inhibit the proteasome function and is a novel proteasome inhibitor. The proteasome inhibitor screened by the invention may become a new generation of proteasome inhibitor which is better in effect, stronger in specificity, smaller in side effect and also plays a role in solid tumors; the proteasome inhibitor can be finally used for preparing drugs for inhibiting tumor cell proliferation and / or inducing tumor cell death, and has important drug and medical clinical values.

Provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. Additionally, provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, in combination with a second active agent selected from the group consisting of an anti-CD20 antibody, an HDAC inhibitor, a proteasome inhibitor, an anti-CD38 antibody, an anti-SLAMF7 antibody, a nuclear export inhibitor, a BCL-2 inhibitor, and an immune checkpoint inhibitor. Also provided herein are combination therapies for treating and / or managing cancer, further comprising dexamethasone as a third active agent.

In a first aspect, the invention relates to a combination of at least one menin inhibitor with at least one immunoproteasome inhibitor for use as medicament, preferably for use in the treatment of leukemia. A second aspect of the invention is related to a pharmaceutical preparation comprising at least one menin inhibitor and at least one immunoproteasome inhibitor, optionally one or more pharmaceutically acceptable carrier(s) and optionally one or more pharmaceutically acceptable adjuvant(s).

The invention belongs to the field of biomedicine, and particularly relates to a screening method of a degradation signal peptide, a fusion protein and a proteasome inhibitor. The invention firstly provides a degradation signal peptide. The degradation signal peptide can mediate degradation of target protein directly or indirectly connected with the degradation signal peptide; the degradation signal peptide comprises a sequence which is the same as a sequence formed by 6-200 amino acids in TMEM8B protein, namely, the degradation signal peptide is of a polypeptide structure containing 6-200 amino acids. The degradation signal peptide provided by the invention is coupled with the target protein, so that the target protein can be completely degraded very efficiently; compared with a wild type full-length TMEM8B-a protein, the degradation signal peptide contains less amino acid, is a direct active site, and is not easy to cover due to space folding of the protein; meanwhile, due to the smaller size, in-vitro artificial synthesis is easier, and downstream application is facilitated.

The present invention relates to combination therapy of an anti-GPRC5D / anti-CD3 bispecific antibody with a proteasome inhibitor. The combination therapy may further include a glucocorticoid.

This disclosure provides combination therapies comprising an anti-BCMA antigen binding protein, such as belantamab mafodotin; an immunomodulatory imide drug (IMiD); a proteasome inhibitor; and a corticosteroid. This disclosure also provides combination therapies for treating newly diagnosed multiple myeloma.

The disclosure herein provides combination therapies for the treatment of cancers such as Leukemia, lymphoma and triple negative breast cancer. The disclosure provides combination therapies of CDK inhibitors, e.g., a CDK inhibitor represented by Formula I:or a pharmaceutically acceptable salt thereof together with a BCL-2 inhibitor or proteasome inhibitor for the treatment of cancer.

The invention belongs to the field of medicines, and discloses application of a reagent for inhibiting phosphorylation of STAT3 and / or reducing the expression level of a 20S proteasome beta 5 subunit in preparation of a sensitizer. The sensitizer is a reagent for improving the sensitivity of the proteasome inhibitor acting on solid tumor cells. A reagent for inhibiting the phosphorylation of STAT3 and / or for reducing the expression level of the 20S proteasome beta 5 subunit is used for preparing a sensitizer for assisting the proteasome inhibitor to improve the sensitivity, and the sensitizer can be used for improving the sensitivity of the proteasome inhibitor when acting on cancer cells. In addition, the invention also discloses a medicine containing the sensitizer.

Methods and corresponding uses are provided for treating disease in a patient, involving the use of sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] so as to ameliorate drug resistance, including resistance to proteasome inhibitors and immunomodulatory imide drugs. The disease may for example be relapsing / refractory multiple myeloma.

The present disclosure provides proteasome inhibitors of Formula (I), useful in treating cancer, such as multiple myeloma and mantle cell lymphoma.

The Artemisinin-Proteasome inhibitor conjugate compounds of the present application are represented by the following compounds having Formula (I) where the substituents R1-R5, X, Y, Y', and Z are defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders, infectious disease, or for providing immunosuppression for transplanted organs or tissues.

Proteasome inhibitors of formula (I), wherein the meanings for the various substituents are as disclosed in the description.

This application provides a pharmaceutical composition and its application for treating liver cancer, relating to the field of biomedical technology. The pharmaceutical composition includes active ingredients, namely the proteasome inhibitor Bortezomib and the Rev-Erb agonist SR9009. By combining the proteasome inhibitor Bortezomib with the Rev-Erb agonist SR9009, synergistic anti-liver cancer activity is observed both in vitro and in vivo, enhancing the mechanism of protein toxicity-induced apoptosis in liver cancer cells. The combined effect of Bortezomib and Rev-Erb agonist SR9009 is significantly superior to either Bortezomib or Rev-Erb agonist alone, overcoming the poor efficacy of Bortezomib monotherapy in liver cancer, and demonstrating significant synergistic effects and clinical application value.

The present disclosure provides a boric acid proteasome inhibitor compound represented by formula I and use thereof as a proteasome inhibitor.