Researchers from the University of Minnesota have presented the discovery and preclinical characterization of a novel potent inhibitor of multidrug resistance-associated protein 1 (MRP1), ZW-1226, that is being developed as a therapeutic candidate for the treatment of multidrug resistant (MDR) cancers.
A study on the posttranslational modification through lactylation of non-histone proteins revealed a mechanism that participates in genome stability and provides resistance to chemotherapy. Scientists from The Second and The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU) identified the lactation of the Nijmegen breakage syndrome 1 (NBS1) protein and the enzymes that participate in this process as a strategic point in cancer therapy.
The adaptation of cancer cells to therapies limits the effectiveness of treatments. However, understanding the mechanisms they use to do it could help reverse them or be used to design more powerful drugs. Scientists at New York University (NYU) have studied the transitions causing resistance and have observed how it develops through a gradual process they have called the “resistance continuum.”
Researchers from Contrafect Corp. have reported on the bactericidal activity of CF-370, a novel engineered lysin with broad-spectrum activity against gram-negative organisms, which are usually more resistant to antibacterial agents than gram-positive bacteria.
Bruton tyrosine kinase (BTK) enzyme inhibitors used to treat B-cell cancers, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma, also produce resistance by causing mutations in the protein. Now, a study on the BTK degrader NX-2127 showed the compound could be effective in eliminating BTK regardless of its mutations.
Researchers have identified a new class of antibiotics that works by blocking the transportation of lipopolysaccharide (LPS) to the outer membrane of the gram-negative bacterium Acinetobacter baumannii. The most advanced member of the class, zosurabalpin (RG-6006, Roche AG), was effective against multiple A. baumannii strains, including carbapenem-resistant and multidrug-resistant strains.
Researchers have used explainable artificial intelligence (explainable AI) to find structurally new antibiotics with minimal toxicity. They reported their findings online in Nature on Dec. 20, 2023. In animal testing, compounds identified via the method showed that they had activity against drug-resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), one of the most serious bacterial public health threats.
A newly discovered antibiotic has been shown to block the synthesis of bacterial cell walls via immutable targets, raising the prospect of a class of drugs that will not lose effect through the development of antimicrobial resistance. Clovibactin, isolated from soil bacteria, targets the cell wall precursor molecules lipid II, lipid III and undecaprenyl phosphate (C55PP), all of which have a pyrophosphate group in common.
Researchers from the U.S. National Institutes of Health and collaborators recently conducted a study investigating the mechanisms of HIV-1 resistance to integrase strand transfer inhibitors (INSTIs), such as the approved drug dolutegravir (DTG). They focused on understanding the mechanisms of resistance caused by mutations at positions 138, 140, and 148 and analyzed combinations of the mutations E138K, G140A/S, and Q148H/K/R, all conferring resistance to INSTIs.
A different class of antibiotics could ease the increasing resistance triggered by some gram-negative bacteria. LpxC inhibitors are not new, but all attempts to develop them have failed due to cardiovascular toxicity or ineffectiveness. A modification of the structure of these compounds may have solved the problem. Duke University scientists demonstrated the preclinical safety and efficacy of an LpxC inhibitor candidate against a wide selection of these pathogens.
RSS
