In an effort to facilitate the discovery of new, improved inhibitors of the metallo--lactamases (MBLs), a new, interactive website called MBLinhibitors.com was developed. Despite considerable efforts from the science community, there are no clinical inhibitors of the MBLs, which are now produced by human pathogens. The website, MBLinhibitors.com, contains a searchable database of known MBL inhibitors, and inhibitors can be searched by chemical name, chemical formula, chemical structure, Simplified Molecular-Input Line-Entry System (SMILES) format, and by the MBL on which studies were conducted. The site will also highlight a "MBL Inhibitor of the Month", and researchers are invited to submit compounds for this feature. Importantly, MBLinhibitors.com was designed to encourage collaboration, and researchers are invited to submit their new compounds, using the "Submit" function on the site, as well as their expertise using the "Collaboration" function. The intention is for this site to be interactive, and the site will be improved in the future as researchers use the site and suggest improvements. It is hoped that MBLinhibitors.com will serve as the one-stop site for any important information on MBL inhibitors and will aid in the discovery of a clinically useful MBL inhibitor.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175331 | PMC |
http://dx.doi.org/10.3390/biom10030459 | DOI Listing |
Antibiotics (Basel)
December 2024
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Metallo-β-lactamases (MBLs) in and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2024
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Previously, we reported that 3--alkyl difluoroquercetins (di-F-Q) potentiates the antimicrobial activity of aztreonam (ATM) against metallo-β-lactamase (MBL)-producing through simultaneous inhibition of MBLs and efflux pumps. However, the ATM-potentiating activity of the 3--alkyl di-F-Q was observed only at high and potentially toxic concentrations (32 mg/L). As both MBLs and efflux pumps reside in the periplasm of Gram-negative bacteria, their inhibitors should accumulate in the periplasmic space.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
December 2024
Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Fribourg, CH-1700, Switzerland.
To evaluate the in-vitro activity of the novel commercially-available drugs, including meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (IPR) as well as cefiderocol (FDC), against carbapenem-resistant Pseudomonas spp. (CRP) isolates. All CRP isolates collected at the Swiss National Reference Laboratory (NARA) over the year 2022 (n = 170) have been included.
View Article and Find Full Text PDFOncogene
December 2024
Department of Hematology, the Second Xiangya Hospital; School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, Hunan, 410011, China.
Multiple myeloma (MM), the world's second most common hematologic malignancy, poses considerable clinical challenges due to its aggressive progression and resistance to therapy. Addressing these challenges requires a detailed understanding of the mechanisms driving MM initiation, progression, and therapeutic resistance. This study identifies the pseudokinase tribble homolog 3 (TRIB3) as a high-risk factor that promotes MM malignancy in vitro and in vivo.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom.
While relative binding free energy (RBFE) calculations using alchemical methods are routinely carried out for many pharmaceutically relevant protein targets, challenges remain. For example, open-source tools do not support the easy setup and simulation of metalloproteins, particularly when ligands directly coordinate to the metal site. Here, we evaluate the performance of RBFE methods for KPC-2, a serine-β-lactamase (SBL), and two nonbonded metal parameter setups for VIM-2, a metallo-β-lactamase (MBL) with two active site zinc ions.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!