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title: Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors
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Read our recent article. Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa. Contact Evotec to learn more"
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# Science Pool

# Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors

Posted by [Evotec](https://news.cyprotex.com/sciencepool/author/evotec) on Sep 30, 2021 7:41:42 PM

*Alastair Parkes, Ph.D, Group Leader, Discovery Chemistry, Evotec UK*

As part of our ongoing efforts at Evotec to tackle AMR through the design of novel antibiotics we have been working with Boston-based X-Biotix in a collaboration focussed on targeting priority Gram-negative pathogens. We are now able to share the story of our work on inhibitors of UDP-N-Acetylglucosamine Acyltransferase (LpxA), a key enzyme in the biosynthetic pathway of the outer membrane lipopolysaccharide of Gram-negative bacteria. Building on hit-finding work at X-Biotix we put together a multi-disciplinary team including Medicinal Chemistry, Computational Chemistry, Structural Biology and DMPK at our Abingdon UK site, *in vitro *and *in vivo *Microbiology and PK at our Alderley Park UK site, and *in vitro* Biology at our site in Hamburg, Germany. Through structure and property-based optimisation we were able to design highly potent inhibitors of *Pseudomonas aeruginosa *LpxA that were active against multi-drug resistant clinical isolates. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against *P. aeruginosa *bacteria. In our paper in the Journal of Medicinal Chemistry we share the optimisation story, along with a significant quantity of activity data that we hope will be useful for other teams working on small molecule strategies to tackle *P. aeruginosa *and other Gram-negative bacteria.

[LEARN MORE](https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c00888)

 Tags: [Antibacterial](https://news.cyprotex.com/sciencepool/tag/antibacterial), [Medicinal Chemistry](https://news.cyprotex.com/sciencepool/tag/medicinal-chemistry), [Articles & Whitepapers](https://news.cyprotex.com/sciencepool/tag/articles-whitepapers), [ADME/DMPK](https://news.cyprotex.com/sciencepool/tag/adme-dmpk), [In vitro Biology](https://news.cyprotex.com/sciencepool/tag/in-vitro-biology), [In vivo Pharmacology](https://news.cyprotex.com/sciencepool/tag/in-vivo-pharmacology), [Anti-Infectives](https://news.cyprotex.com/sciencepool/tag/anti-infectives), [Antimicrobial resistance](https://news.cyprotex.com/sciencepool/tag/antimicrobial-resistance)