This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for suicidal ideation in veterans.
The investigators hypothesize that the administration of a naturally occurring dietary supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this study is to determine whether 4 weeks of uridine supplementation is an effective treatment for suicidal ideation in veterans, when compared to a group taking a placebo.

Start Date02 Apr 2018

Sponsor / Collaborator

VA Office of Research and Development

NL-OMON24695 / RecruitingNot Applicable

Bioequivalence of uridine bioavailability in healthy elderly after bolus intake of a nucleotide and an alternative ingredient.

Start Date20 Jul 2015

Sponsor / Collaborator-

100 Clinical Results associated with Uridine

100 Translational Medicine associated with Uridine

100 Patents (Medical) associated with Uridine

1,222

Literatures (Medical) associated with Uridine

01 Jan 2025·ANTIVIRAL RESEARCH

Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4′-fluorouridine

Article

Author: Scheibner, David ; Dobbelstein, Matthias ; Dickmanns, Antje ; Mühlberger, Elke ; Balkema-Buschmann, Anne ; Schrell, Leon ; Graaf-Rau, Annika ; Baumgärtner, Wolfgang ; Reineking, Wencke ; Müller, Martin ; Hume, Adam J ; Finke, Stefan ; Störk, Theresa ; Olejnik, Judith ; Fuchs, Hannah L ; Diederich, Sandra

RNA viruses present a constant threat to human health, often with limited options for vaccination or therapy. Notable examples include influenza viruses and coronaviruses, which have pandemic potential. Filo- and henipaviruses cause more limited outbreaks, but with high case fatality rates. All RNA viruses rely on the activity of a virus-encoded RNA-dependent RNA polymerase (RdRp). An antiviral nucleoside analogue, 4'-Fluorouridine (4'-FlU), targets RdRp and diminishes the replication of several RNA viruses, including influenza A virus and SARS-CoV-2, through incorporation into nascent viral RNA and delayed chain termination. However, the effective concentration of 4'-FlU varied among different viruses, raising the need to fortify its efficacy. Here we show that inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme essential for pyrimidine biosynthesis, can synergistically enhance the antiviral effect of 4'-FlU against influenza A viruses, SARS-CoV-2, henipaviruses, and Ebola virus. Even 4'-FlU-resistant mutant influenza A virus was re-sensitized towards 4'-FlU by DHODH inhibition. The addition of uridine rescued influenza A virus replication, strongly suggesting uridine depletion as a mechanism of this synergy. 4'-FlU was also highly effective against SARS-CoV-2 in a hamster model of COVID. We propose that the impairment of endogenous uridine synthesis by DHODH inhibition enhances the incorporation of 4'-FlU into viral RNAs. This strategy may be broadly applicable to enhance the efficacy of pyrimidine nucleoside analogues for antiviral therapy.

01 Dec 2024·EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Characterising and preventing the gut microbiota's inactivation of trifluridine, a colorectal cancer drug

Article

Author: Thomaidou, Stavrina ; Sangfuang, Nannapat ; Globisch, Daniel ; Favaron, Alessia ; McCoubrey, Laura E. ; Shen, Chenghao ; McCoubrey, Laura E ; Basit, Abdul W ; Mwasambu, Sydney ; Basit, Abdul W. ; Orlu, Mine

The gut microbiome can metabolise hundreds of drugs, potentially affecting their bioavailability and pharmacological effect. As most gut bacteria reside in the colon, drugs that reach the colon in significant proportions may be most impacted by microbiome metabolism. In this study the anti-colorectal cancer drug trifluridine was used as a model drug for characterising metabolism by the colonic microbiota, identifying correlations between bacterial species and individuals' rates of microbiome drug inactivation, and developing strategies to prevent drug inactivation following targeted colonic delivery. High performance liquid chromatography and ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry demonstrated trifluridine's variable and multi-route metabolism by the faecal microbiota sourced from six healthy humans. Here, four drug metabolites were linked to the microbiome for the first time. Metagenomic sequencing of the human microbiota samples revealed their composition, which facilitated prediction of individual donors' microbial trifluridine inactivation. Notably, the abundance of Clostridium perfringens strongly correlated with the extent of trifluridine inactivation by microbiota samples after 2 hours (R² = 0.8966). Finally, several strategies were trialled for the prevention of microbial trifluridine metabolism. It was shown that uridine, a safe and well-tolerated molecule, significantly reduced the microbiota's metabolism of trifluridine by acting as a competitive enzyme inhibitor. Further, uridine was found to provide prebiotic effects. The findings in this study greatly expand knowledge on trifluridine's interactions with the gut microbiome and provide valuable insights for investigating the microbiome metabolism of other drugs. The results demonstrate how protection strategies could enhance the colonic stability of microbiome-sensitive drugs.

01 Nov 2024·NEUROCHEMISTRY INTERNATIONAL

Traditionally used edible medicinal plants protect against rotenone induced toxicity in SH-SY5Y cells-a prospect for the development of herbal nutraceuticals

Article

Author: Meitei, Heikrujam Nilkanta ; Hijam, Aruna Chanu ; Haobam, Reena ; Koijam, Arunkumar Singh ; Nongthombam, Pooja Devi ; Tongbram, Yaiphabi Chanu ; Rajashekar, Yallapa

Plants are good sources of pharmacologically active compounds. The present study aimed to examine the neuroprotective potentials of the methanol extracts of Salix tetrasperma Roxb. leaf (STME) and Plantago asiatica L. (PAME), two edibles medicinal plants of Manipur, India against neurotoxicity induced by rotenone in SH-SY5Y cells. Free radical quenching activities were evaluated by ABTS and DPPH assays. The cytotoxicity of rotenone and the neuronal survival were assessed by MTT assay and MAP2 expression analysis. DCF-DA, Rhodamine 123 (Rh-123), and DAPI measured the intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and apoptotic nuclei, respectively. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were also assessed. LC-QTOF-MS analysis was performed for the identification of the compounds present in STME and PAME. The study showed that both the plant extracts (STME and PAME) showed antioxidant and neuroprotective capabilities in rotenone-induced neurotoxicity by preventing oxidative stress through the reduction of intracellular ROS levels and reversing the activities of GPx, SOD, and CAT caused by rotenone. Further, both plants prevented apoptotic cell death by normalizing the steady state of MMP and protecting nuclear DNA condensation. LC-QTOF-MS analysis shows the presence of known neuroprotective compounds like uridine and gabapentin in STME and PAME respectively. The two plants might be an important source of natural antioxidants and nutraceuticals with neuroprotective abilities. This could be investigated further to formulate herbal nutraceuticals for the treatment of neurodegenerative disease like Parkinson's disease.

News (Medical) associated with Uridine

25 Oct 2023

·www.biospace.com

EnginZyme Produces Key mRNA Vaccine Ingredient Using Biocatalysis

EnginZyme and Ajinomoto Bio-Pharma Services have developed a patented process to manufacture pseudouridine at industrial scale using biocatalysis in a sustainable, low-waste, patented process carried out in a cGMP* facility EnginZyme is in talks to help alleviate supply chain difficulties in low- and middle-income countries 2023 Nobel laureates discovered how pseudouridine could make mRNA suitable for vaccines STOCKHOLM--(BUSINESS WIRE)-- EnginZyme AB, a deep-tech company whose cell-free biomanufacturing technology uses the power of enzymes to create sustainable products and processes for a variety of industries, announced that it had patented a process to synthesize pseudouridine, a key ingredient in mRNA COVID-19 vaccines. EnginZyme and its CDMO partner, Ajinomoto Bio-Pharma Services, specialized in scale up and cGMP* manufacturing of small molecules and other high-value fine chemicals, said they could provide pseudouridine at a discount to buyers taking part in efforts to bolster the global supply chain of vaccine ingredients. The companies said they had already synthesized enough pseudouridine for more than half a billion doses of vaccine in a facility that is fully cGMP* compliant. The enzymatic process EnginZyme has perfected is cleaner and more efficient than the chemical synthesis methods currently used. A critical impurity, alpha-pseudouridine, which is a by-product of the chemical synthesis of beta-pseudouridine, is eliminated in EnginZyme's patented enzymatic synthesis. For more technical information, see our website. The 2023 Nobel Prize for Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman, the pair who discovered that changing a chemical building block of messenger RNA – substituting pseudouridine for uridine – eliminated an inflammatory side effect that stalled development of vaccines based on mRNA. They made this discovery more than 15 years before the COVID-19 pandemic. During the COVID-19 crisis, the World Health Organization found that low- and middle-income countries were suffering from a lack of vaccine doses amid production and supply constraints, hoarding by wealthy countries, and prioritization of sales to governments that could pay the highest prices. "Not long after we discovered the process for making pseudouridine, we realized that we could produce a pure version at scale for much less than it was going for on the market," said Karim Engelmark Cassimjee, CEO of EnginZyme. "We decided the right thing to do would be to use this discovery to help make the global healthcare supply chain more resilient." He added that academic and nonprofit organizations could apply to receive free samples for research purposes. Geert Schelkens, R&D Manager at Ajinomoto Bio-Pharma Services, said: "The scale-up of a biocatalytic process and a green workup results in a drastic reduction of the compound's footprint. This achievement nicely aligns with our sustainability ambitions. This project with EnginZyme has been particularly rewarding because of its potential to improve the global supply chain for vaccine ingredients.” N1-methylpseudouridine-5’-triphosphate, which is derived from pseudouridine, helps stabilize and reduce the immunogenicity of mRNA. Messenger RNA technology made headlines through the successful COVID-19 vaccines produced by Pfizer-BioNTech and Moderna, and since then, an increasing number of early-stage therapeutics and emerging vaccines have been based on the technology. "Synthesizing pseudouridine with enzymes is so much more efficient than the chemical synthesis that is common today," said Matthew Thompson, head of enzyme development and innovation at EnginZyme. "It's a perfect example of what we are striving for: zero waste, less energy, and a cleaner result. We want to apply this across the spectrum of chemical manufacturing." *Current Good Manufacturing Practice regulations, enforced by the U.S. FDA, provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. About EnginZyme EnginZyme is changing chemistry for good. We are enabling the shift to biomanufacturing by unlocking the power of enzymes for more cost-efficient and sustainable production of everyday products. Our patented enzyme immobilisation technology enables biomanufacturing without living organisms. It can be deployed using the same tools and techniques used in traditional chemical manufacturing, with lower costs and a much smaller environmental footprint. Based in Stockholm, EnginZyme is a growing company with a multidisciplinary team of experts in biocatalysis, organic chemistry, enzyme and process engineering, as well as AI and machine learning. This elite team is uniquely positioned to develop complete processes from techno-economic analysis all the way to industrial manufacture, incorporating a high degree of automation for safe, rapid, and reliable development. EnginZyme has been recognised as a Technology pioneer by the World Economic Forum and was selected to the Global Cleantech 100 list in 2022 and 2023. About Ajinomoto Bio-Pharma Services Ajinomoto Bio-Pharma Services is a fully integrated contract development and manufacturing organization with sites in Belgium, United States, Japan, and India, providing comprehensive development, cGMP manufacturing, and aseptic fill finish services for small and large molecule APIs and intermediates. Ajinomoto Bio-Pharma Services offers a broad range of innovative platforms and capabilities for pre-clinical and pilot programs to commercial quantities, including high potency APIs (HPAPI), biocatalysis, continuous flow manufacturing, Corynex® protein expression technology, oligonucleotide synthesis, antibody drug conjugations (ADC), and more. Ajinomoto Bio-Pharma Services is dedicated to providing a high level of quality and service to meet our client’s needs. Learn more: View source version on businesswire.com: Contacts Business development Karl Johan Tärbe karljohan@enginzyme.com Media Bogert-Magnier Communications James Connell jim@bogert-magnier.com +33 6 2152 1955 Elodie Doan Van elodie@bogert-magnier.com +33 6 8099 8881 Source: EnginZyme AB View this news release online at:

VaccinemRNA

22 May 2023

·www.pmlive.com

Researchers at ICR London discover new nutrient source for cancer growth

Researchers at the Institute of Cancer Research (ICR), London and the University of Michigan in the US have made a major discovery of the changing 'diet' within pancreatic cancer cells, enabling the growth of the cancer. The findings were published in Nature and funded by Pancreatic Cancer UK, the Ian Harty Charitable Trust and the National Institutes of Health (NIH) in the US. Pancreatic cancer is responsible for 5.2% of all cancer deaths in the UK, with the fifth highest cancer mortality rate, and is predicted to have the fourth highest cancer mortality rate by 2030. The newly discovered nutrient source, uridine, is a molecule that replaces glucose in pancreatic cancer cells to adapt as a fuel source, having the potential of becoming a new treatment strategy for the aggressive form of cancer. Researchers believe that uridine could also help fuel other cancers including lung, stomach and brain cancer. Uridine is found in the body and is required for a healthy metabolism. Despite this, uridine acts as a supply to pancreatic cancer cells once glucose is in short supply. Using uridine, the cancer cells are able to continue growing, even if their usual food source is insufficient. Phenotypic microarray, a new technique that allows the testing of thousands of cell characteristics at once, enabled researchers to find that uridine is broken down by the enzyme, uridine phosphorylase-1 (UPP1), to produce a new form of sugar, ribose, as fuel for cells. Team leader in systems and precision cancer medicine at the ICR, London, Dr Anguraj Sadanandam, said: “Next, we will explore ways to use uridine to monitor existing therapy responses in pancreatic cancer and hopefully develop new drugs targeting UPP1.” By removing the UPP1 gene in mice, researchers found it stopped pancreatic cells from accessing uridine and largely halted tumour growth. High levels of UPP1 were also linked to the poor survival of people with pancreatic cancer, as well as other types of cancer. Although there are no approved drugs used to block UPP1 in humans, the new findings increase the potential of finding a new treatment to combat it. Professor Kristian Helin, chief executive of the ICR, London, clarified that researchers are "using cancer's own growth tactics against it".

18 May 2023

·www.sciencedaily.com

Cancer cells use a new fuel in absence of sugar

Researchers have discovered a new nutrient source that pancreatic cancer cells use to grow. The molecule, uridine, offers insight into both biochemical processes and possible therapeutic pathways. The findings show that cancer cells can adapt when they don't have access to glucose. Researchers at the University of Michigan Rogel Cancer Center have discovered a new nutrient source that pancreatic cancer cells use to grow. The molecule, uridine, offers insight into both biochemical processes and possible therapeutic pathways. The findings, published in Nature, show that cancer cells can adapt when they don't have access to glucose. Researchers have previously identified other nutrients that serve as fuel sources for pancreatic cancer; this study adds uridine to the catalog. Pancreatic tumors have few functioning blood vessels and can't easily access nutrients that come from the bloodstream, like glucose. Costas Lyssiotis, Ph.D., Maisel Research Professor of Oncology and lead investigator of the study, explained that without the right nutrients, the cancer cells get hungry. "We know they still grow, obviously, but what are they using to grow?" he said. "These findings show that, under certain circumstances, uridine is one of those fuels." Asked about impact, Zeribe Nwosu, Ph.D., one of the co-first authors in the study, says "the ability of cancer to switch to alternative nutrients has fascinated me for a long time. Blocking such compensatory switches could lead us to new treatments and that's the door we hope this study will open." Uridine is present in the tumor microenvironment, but its exact source, and how cancer cells access it, remains a mystery. "Part of the picture is it's in the bloodstream, but we don't know where it's coming from specifically," said Lyssiotis. "Likely, it's coming from multiple places, and so far we haven't been able to pin it to a single source." Events that Lyssiotis refers to as "times of crisis" -- when cells don't have enough nutrients, because of limited blood access and/or intense competition between cells -- could be a clue as to why, and where, cells turn to uridine. "The cancer cells seem to be sensing the concentrations of glucose and uridine in the local environment to inform their adaptation," says Matt Ward, another co-first author. Lyssiotis' team recognize this unknown regulatory process, as well as a cancer-promoting mutation in the KRAS gene, which is common in pancreatic cancer, as two ways that cancer cells control their usage of uridine. Lyssiotis and his team have been working on this research for nearly a decade alongside their collaborators in the Sadanandam lab at the Institute for Cancer Research in London. They used a technology that screens hundreds of different nutrients to see which ones support pancreatic cancer growth. Typically, researchers look at standard nutrients like sugar, protein and fat, but Lyssiotis's team took an unbiased approach. "We used a large panel with over 20 pancreatic cell lines and around 200 different nutrients to assess different ways pancreatic cancer cells grow," he explained. "What do they actually metabolize? This method led us to discover uridine." This method offers therapeutic insight, too. The findings showed that uridine is metabolized by the enzyme uridine phoshorylase-1, or UPP1. Blocking UPP1 had a major impact on the growth of pancreatic tumors in mice, findings that suggest the importance of testing drugs that block uridine as possible new treatment options. "There's potential to better understand and treat pancreatic cancer with new drug targets and new therapeutic approaches," said Sadanandam, co-author on the study. More research is needed to determine the best way to move this discovery to the clinic.

100 Deals associated with Uridine

External Link

KEGG	Wiki	ATC	Drug Bank
D00342	Uridine	-	DB02745

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bipolar I disorder	Phase 2	US	Repligen Corp.	01 Mar 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


5288 (AAN2020)	Not Applicable	Epileptic encephalopathy	-	Uridine supplementation	ueygirfejy(sgxizecibv) = ljlilrbbyy aoyynexdos (opbawfbrme )	-	14 Apr 2020
ACTG 5229 \| A5229 (Pubmed \| AIDS)	Not Applicable	Lipodystrophy	165	NucleomaxX	gvcellzkbv(wjtfdzsvbe) = fytnnczrrj dttmlongdm (xoxaygeckh )	-	23 Oct 2010
				Placebo	gvcellzkbv(wjtfdzsvbe) = zrlozzuyyy dttmlongdm (xoxaygeckh )
IAS2009	Not Applicable	Lipodystrophy	45	Uridine	kzxpcyoffv(jrlmodjisp) = sardhedpez surordmigl (eknabnjbto ) View more	-	01 Jan 2009
				Pravastatin	kzxpcyoffv(jrlmodjisp) = mcirhhsylr surordmigl (eknabnjbto )
SFN2008	Not Applicable	Brain Injuries, Traumatic	-	Uridine 16mg/kg	jvupegmwxw(irzcntlpch) = aqbpdqyjxb ysthvpbonn (grogzzhett )	-	18 Nov 2008
				Uridine 32mg/kg	jvupegmwxw(irzcntlpch) = cwxxeypvjs ysthvpbonn (grogzzhett )
EULAR2007	Not Applicable	Mitochondrial Myopathies	9	Mitocnol	pvhmakhuum(bbpqmiutaf) = iyejqudeas xbmlnuzdkn (oeursqqbbf ) View more	Positive	13 Jun 2007
				Zidovudine	pvhmakhuum(bbpqmiutaf) = bmwouwhbyj xbmlnuzdkn (oeursqqbbf ) View more
IAS2003	Not Applicable	-	-	Uridine	laqlzqzfsk(rkxlxtngir) = fully restored mqqdquornw (wwhhvclhgh ) View more	-	01 Jan 2003

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