Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections |
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Authors: | Wei-Chu Xu Michael H Silverman Xiang Yang Yu George Wright Neal Brown |
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Institution: | 1. Department of Chemistry, Worcester State University, 486 Chandler Street, Worcester, MA 01602, USA;2. Acurx Pharmaceuticals LLC, 22 Camelot Court, White Plains, NY 10603, USA |
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Abstract: | Despite the growing global crisis caused by antimicrobial drug resistance among pathogenic bacteria, the number of new antibiotics, especially new chemical class of antibiotics under development is insufficient to tackle the problem. Our review focuses on an emerging class of antibacterial therapeutic agents that holds a completely novel mechanism of action, namely, inhibition of bacterial DNA polymerase IIIC. The recent entry of this new class into human trials may herald the introduction of novel drugs whose novel molecular target precludes cross-resistance with existing antibiotic classes. This review therefore examines the evolution of DNA pol IIIC inhibitors from the discovery of 6-(p-hydroxyphenylazo)uracil (HPUra) in the 1960s to the development of current first-in-class N7-substituted guanine drug candidate ACX-362E, now under clinical development for the treatment of Clostridioides difficile infection. |
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Keywords: | Corresponding author Tel : +1 508 929 8294 fax: +1 508 929 8171 ACX-362E Antibiotic resistance DNA polymerase Gram(+) bacteria Pol IIIC |
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