After years of research, scientists at Duke University have created a synthetic antibiotic known as LPC-233 that has shown significant effectiveness against gram-negative bacteria such as E. coli and Salmonella. This antibiotic disrupts the synthesis of the outer membrane lipid in these bacteria and has shown impressive results in animal tests, displaying the potential to tackle resistant urinary tract infections with minimal resistance mutation rates.
The journey towards this discovery spanned decades, involving numerous researchers, innovative patents, and the founding of a new startup. The development process focused on a unique approach to fight gram-negative bacteria that often cause urinary tract infections. The synthetic molecule LPC-233 acts rapidly and has proven to be enduring in animal testing.
The molecule functions by hindering a bacterium’s ability to create its outer lipid layer, effectively killing it. As per Pei Zhou, the lead investigator and biochemistry professor at Duke, LPC-233 has been highly potent against every gram-negative bacterium it was tested against. This was confirmed by co-authors at the University of Lille in France, who tested it on 285 bacterial strains, successfully killing them all.
The new compound can reduce bacterial viability by 100,000-fold in only four hours. Furthermore, it can survive all the way to the urinary tract after oral administration, making it a potential critical tool against persistent UTIs.
Studies revealed “exceedingly low rates of spontaneous resistance mutations” in these bacteria. In animal trials, the compound was effective when given orally and intravenously or injected into the abdomen, and even saved mice from a potentially lethal dose of multidrug-resistant bacteria.
The path to this compound was extensive, demanding precision and safety. The late Christian Raetz, former Duke Biochemistry Chair, initiated the search decades ago, proposing a blueprint in the 1980s that took over twenty years to fully identify.
The target of the new drug is an enzyme called LpxC, essential for creating the outer membrane lipid in gram-negative bacteria. Following previous failures at Merck & Co., the team at Duke worked on over 200 versions of the enzyme inhibitor, leading to the success of compound number 233, LPC-233.
This compound fits and blocks the LpxC enzyme, “jamming the system,” and works through a two-step process that makes it more stable and long-lasting, contributing to its potency. Zhou explained that the semi-permanent effect of the inhibitor on the enzyme enhances its effectiveness.
Multiple patents are being filed, and Zhou has co-founded Valanbio Therapeutics, Inc., to bring LPC-233 to phase 1 clinical trials to evaluate its safety and efficacy in humans. The cardiovascular safety of the compound still needs human testing.
David Gooden at the Duke Small Molecule Synthesis Facility accomplished the large-scale synthesis of LPC-233, with assistance from other researchers in in vivo studies, mass spectrometry, and pharmacokinetics analysis. The project was supported by grants from various institutions, including the National Institutes of Health, the North Carolina Biotechnology Center, and the National Cancer Institute Comprehensive Cancer Center Core Grant.
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Frequently Asked Questions (FAQs) about fokus keyword LPC-233
What is LPC-233, and who developed it?
LPC-233 is a synthetic antibiotic created by researchers at Duke University, designed to combat gram-negative bacteria like E. coli and Salmonella by disrupting their outer membrane lipid synthesis.
What types of bacteria can LPC-233 target?
LPC-233 can target gram-negative bacteria, including Salmonella, Pseudomonas, and E. coli, which are often responsible for urinary tract infections.
How does LPC-233 work against bacteria?
LPC-233 works by interfering with a bacterium’s ability to make its outer lipid layer. It fits a binding spot on the LpxC enzyme essential for lipid formation, inhibiting its function.
Has LPC-233 been tested on animals, and what were the results?
Yes, LPC-233 has been tested on animals, demonstrating remarkable efficacy. It reduced bacterial viability by 100,000-fold within four hours and showed potential to combat resistant urinary tract infections.
Who is leading the research on LPC-233?
The research on LPC-233 is led by Pei Zhou, a professor of biochemistry at the Duke School of Medicine.
What are the potential applications of LPC-233?
The compound may become a vital tool against stubborn urinary tract infections (UTIs) and could be effective against bacteria highly resistant to commercial antibiotics.
Are there any plans for human trials of LPC-233?
Yes, multiple patents are being filed, and a company called Valanbio Therapeutics, Inc. has been co-founded to bring LPC-233 through phase 1 clinical trials to assess safety and efficacy in humans.
How long did it take to develop LPC-233?
The search for this compound took decades, reflecting the specificity and safety required of the synthetic molecule. The research journey started in the 1980s and involved extensive work to reach this point.
More about fokus keyword LPC-233
- Science Translational Medicine
- Duke University School of Medicine
- National Institutes of Health
- North Carolina Biotechnology Center
- National Cancer Institute Comprehensive Cancer Center Core Grant
