‘We are actively progressing this new drug type towards clinical trials in people…’
Researchers have found that the action of enzymes called metallo-beta-lactamases (MBLs), which break down carbapenem antibiotics, can be blocked by the use of indole carboxylates, a new class of enzyme blocker.
The work, which has been published in the journal Nature Chemistry, has been carried out by researchers from the Ineos Oxford Institute for Antimicrobial Research, at the University of Oxford, in collaboration with several institutions across Europe. The research was funded by the Innovative Medicines Initiative, through the European Lead Factory and the European Gram-Negative Antibacterial Engine programmes.
The researchers said that they screened ‘hundreds of thousands of chemicals’ to see which would attach tightly to MBLs to stop them working, and which didn’t react with human proteins, leading to the discovery of the indole carboxylates as promising new candidates. Following work to make drugs as effective as possible, and testing in combination with carbapenems against multi-drug resistance bacteria, the potential new drugs were found to be five times more potent at treating severe bacterial infections than carbapenems alone. The researchers noted that the drugs showed only mild side effects in mice.
Professor Christopher Schofield, Academic Lead (Chemistry), Ineos Oxford Institute at the University of Oxford said; ‘The collaborative efforts of academics and industry scientists have discovered a brand new class of drug that can shut down one of the ways bacteria fight back against antibiotics. The research is the culmination of years of work, from screening huge libraries of chemicals, through to testing the best drug candidates in pre-clinical studies in lab. We are actively progressing this new drug type towards clinical trials in people, most importantly in lower and middle income countries where resistance to carbapenem antibiotics is widespread.’
DOI: 10.1038/s41557-021-00831-x
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