8 results about "Proteasome inhibitor" patented technology

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%.

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).

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 invention relates to the combination therapy of anti-GPRC5D / anti-CD3 bispecific antibodies with proteasome inhibitors. The combination therapy may further comprise a glucocorticosteroid.

The present disclosure relates to therapeutic combinations comprising an anti- KMA antibody and a proteasome inhibitor for the treatment of multiple myeloma. The present disclosure also relates to methods of treating multiple myeloma in subjects with high serum cytokine levels.

Compounds of formula (I), (II), and (III) having the structure shown below are presented: wherein R-R6 are defined herein. These molecules work as proteasome inhibitors and bind to the RPN13 subunit of the 19S regulatory particle, and can be used in methods of treating a condition or a disease, such as cancer, in a mammal.