Neomycin Sulfate

Maria Duca speaking at the ELRIG Drug Discovery conference in London, UK. Credit: Frankie Fattorini/ GlobalData As interest mounts in using RNA as a therapeutic target, a group at the Institute of Chemistry in Nice is overcoming the need for lengthy, expensive screening of candidate compounds with a rational design approach. Dr. Maria Duca, head of the Targeting of Nucleic Acids team, outlined her team’s novel approach to RNA-targeting drug discovery, in a presentation today (3 October) at the ELRIG Drug Discovery 2024 conference in London, UK. Duca pointed out, “If we look at currently marketed drugs, these mainly target proteins, but these proteins represent a very small percentage of what the human genome encodes. If we take into account non-coding RNAs as potential targets for drugs, we could really widen the landscape of current medicinal chemistry.” However, according to Duca, “The problem is that you don’t have many rational design methodologies in order to design your compound specific for a particular RNA target. So, everything is mostly based on screenings.” Instead of mass screenings, Duca and her team assemble and test novel molecular conjugates to be target-specific and therapeutically effective. Duca said some of the more promising candidates created using this approach have potential in oncological and infectious disease indications. See Also: Advancing Pharmaceutical Security: The Role of SECURtracers in On-Dose Authentication Healthcare Payers for the Pharmaceutical Industry Duca outlined the discovery process behind her team’s conjugate against microRNA-327 (miRNA-327), an oncogenic RNA implicated in gastric cancer. The team conjugated the aminoglycoside neomycin with different artificial nuclear bases. The conjugates produced were screened in vitro for their selectivity and inhibitive activity towards miRNA-327. Promising candidates from these screens could then be studied in vivo. In gastrinoma cancer cells, which are characterised by miRNA-327 overexpression, the team found the chosen candidates inhibited cell proliferation in a dose-dependent manner. Imaging the conjugate-RNA interactions allowed them to further refine these neomycin conjugates for their miRNA-327 affinity and inhibition. Through this same process of design, in vitro screening, in vivo testing, and further structural refinement of conjugates, Duca and her team have produced therapeutic candidates targeting other RNAs. For example, they built another library of candidates targeted against miRNA-21 which is overexpressed in glioblastoma, a type of brain cancer. Applying the same rational design process, researchers produced candidates that inhibited glioblastoma cell proliferation, in a way that was comparable with the efficacy of temozolomide, one of the few palliative treatments for glioblastoma, marketed as Kimozo / Kizfizo by Orphelia Pharma. mRNA vaccine coverage on Pharmaceutical Technology (Or Clinical Trials Arena) is supported by Trilink . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper mRNA capping: low cost, high reward Are you aware of the latest mRNA capping techniques? The success of mRNA-based Covid vaccines has seen the technology boom in popularity – but capping is an essential part of the manufacturing process, and pharmaceutical firms face a range of choices on how to do it. This free whitepaper assesses differences in price, time, complexity and availability for the methods on offer – and provides essential insights on TriLink’s trailblazing CleanCap® approach. Fill in your details to find out more. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Trilink Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Trilink Thematic and that your personal data will be used as described in their Privacy Policy

In a new study, researchers found that antibiotics have sex-specific effects on the gut microbiome makeup of male and female laboratory rats. The findings could have implications for using the drugs in humans to treat or prevent bacterial infection. In a new study, researchers at Cedars-Sinai found that antibiotics have sex-specific effects on the gut microbiome makeup of male and female laboratory rats. The findings, published in the journal Frontiers in Microbiology, could have implications for using the drugs in humans to treat or prevent bacterial infection. "We found that giving the rats a multidrug antibiotic cocktail resulted in significant and sex-specific changes in both the stool, or large intestine, and the small bowel. For example, greater loss of the diversity of the microbes in both stool and small bowel was observed in the male rodents than in the females," said Ruchi Mathur, MD, the study's principal investigator. "Changes in the diversity of the gut microbiome could have a negative impact. Previous studies of intestinal health have demonstrated that overall microbial diversity promotes vitality and resilience, often making for a healthier gut," said Mathur, an endocrinologist. In the controlled study, investigators from the Cedars-Sinai Medically Associated Science and Technology (MAST) Program compared the composition of the gut microbes of the male and female rats before, during and after treatment with broad-spectrum antibiotics, including vancomycin, ampicillin, metronidazole, and neomycin. "We followed the rats for a period after the antibiotics were stopped and found that many of the sex-specific changes we observed during treatment remained. The constellation of microbes in the gut did not return to their original, pre-antibiotic compositions in either sex during the duration of the study," said research associate Gonzalo Parodi, first author of the paper. Some studies have identified sex-specific effects of antibiotics on the large bowel (stool) microbiome in mice. But Cedars-Sinai investigators emphasize that this is the first study to also examine changes in the small bowel microbiome induced by antibiotics and to also use male and female rats that had no significant differences in microbiome composition prior to treatment. "It is difficult to tease out the impact of the drugs if the lab animals' gut microbiomes are different to begin with. We used rats with similar gut profiles right out of the gate. This allowed us to pinpoint changes in the microbiomes of the male and female rats that could be attributed specifically to the impact of the antibiotics during and after exposure to the medicines," said Mark Pimentel, MD, director of the MAST program and a co-author of the study. More studies are needed using different combinations of antibiotics and exposure times. Investigators say if these findings hold true for humans, the research could have implications for the way antibiotics are prescribed. "Sex is a biological variable, and like any variable, it needs to be taken into consideration in basic and medical research. Currently, we consider factors such as kidney function and weight when dosing medications for patients. Depending on the results of further research, specifically in humans, the sex of patients may one day be an important consideration when prescribing antibiotics," said Mathur.