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

13,952

Literatures (Medical) associated with Uridine

31 Dec 2025·Future Science OA

Evaluating cytidine, uridine, and gabapentin combinations for pain modulation and p-CREB expression in neuropathic model

Article

Author: Alzaghari, Lujain F. ; Qnais, Esam Y. ; Barakat, Muna ; Al-Najjar, Mohammad A. A. ; Chellappan, Dinesh Kumar ; Alqudah, Abdelrahim ; Athamneh, Rabaa Y.

AIMS:

To evaluate the analgesic and neuroprotective effects of cytidine, uridine, and gabapentin-administered alone and in combination-in models of diabetic neuropathy and formalin-induced acute and inflammatory pain.

MATERIALS & METHODS:

Oral doses of cytidine, uridine, and gabapentin (100 mg/kg each) were administered to rats with streptozotocin-induced diabetic neuropathy and in a formalin test model. Behavioral responses were recorded at 30, 60, and 120 minutes following treatment after five weeks of diabetes induction. Spinal cord p-CREB expression was measured to assess molecular changes, and pretreatments with naloxone, yohimbine, and methysergide were employed to explore opioid, adrenergic, and serotonergic contributions.

RESULTS:

All treatments significantly reduced formalin-induced pain in both acute and inflammatory phases (p < 0.05; p < 0.001) and increased mechanical pain thresholds in the diabetic neuropathy model at all-time points (p < 0.05). Combination therapy proved more effective than gabapentin alone (p < 0.05) and was associated with decreased spinal p-CREB levels, indicating altered anti-nociceptive signaling.

CONCLUSIONS:

The combined use of cytidine, uridine, and gabapentin enhances analgesia and neuroprotection compared to monotherapy, supporting its potential as a novel, analgesic-free treatment strategy for diabetic neuropathy.

01 Sep 2025·TALANTA

One-stop solution for wide polar range compounds: Preparation and application of quaternary ammonium salt molecular cage stationary phase

Article

Author: Li, Zhen ; Lan, Tao ; Liu, Sheng ; Pei, Dong ; Zhu, He ; Ding, Ruifang ; Lv, Mei ; Wang, Litao ; Zhang, Yangyang ; Zuo, Ying ; Hu, Jinxia

The separation and analysis of complex samples with wide polar range on a singular column is always a difficult problem in separation and analysis science. In this study, the RCC3-R molecular cage modified with the quaternary ammonium salt stationary phase (RCC3-GQ@silica) was successfully prepared and applicated in the separation of wide polar range compounds. In the Reverse Phase Liquid Chromatography (RPLC) mode, due to the hydrophobicity and π-π interactions provided by the cyclohexane and benzene rings in the molecular cage structure, this stationary phase demonstrated effective separation capabilities for alkylbenzenes, polycyclic aromatic hydrocarbons, phenols, and anilines. In the Hydrophilic Interaction Liquid Chromatography (HILIC) mode, the study explored the separation performance of this stationary phase for sugars and inorganic salts. Utilizing a mixed mode of HILIC/RPLC/Ion Exchange Chromatography (IEC), effective separation was achieved for sulfonamides, nucleosides, acids, and amino acids, indicating good separation effects for medium to strongly polar compounds as well as various hydrophilic compounds. Combining various separation modes, the RCC3-GQ@silica stationary phase successfully separated 91 compounds across 15 categories. These results not only demonstrate the potential of the stationary phase in expanding the range of polarities of analyzable compounds and achieving multipurpose use on a single column, but also confirm its effective separation of nucleosides in pure water systems, further emphasizing the significant application potential of RCC3-GQ@silica stationary phase in the field of green chemistry.

01 Sep 2025·TALANTA

Protein-inorganic hybrid flowers with a two-stage accelerated strategy for stimulated activation of CRISPR/Cas12a enhance polynucleotide kinase biosensing

Article

Author: Wu, Hai ; Wang, Qi ; Xia, Juan ; Yang, Shuo ; Fan, Suhua ; Li, Yang ; Chen, Xiumei

Polynucleotide kinases (PNK) play a crucial role in DNA damage repair and are closely associated with specific diseases, making them promising targets for therapeutic intervention. In this study, we propose a two-stage accelerated strategy that utilizes protein-inorganic hybrid flowers (PHFs) to enhance the performance of the terminal deoxynucleotidyl transferase (TdT)-combined CRISPR/Cas12a system (TCS) for efficient detection of PNK activity. In TCS, the participation of PHFs confines the substrate probes (SPs) to a limited space, thereby significantly enhancing the local concentration of phosphorylated 3' termini of SPs and effectively promoting the enzymatic reaction kinetics as the first step in the accelerated strategy. Upon encountering the target PNK, the phosphorylated 3' termini were promptly recognized and dephosphorylated to 3'-OH termini. Subsequently, TdT catalyzed the assembly of deoxyadenosine triphosphates (dATPs) without a template, rapidly activating the CRISPR/Cas12a system by forming multiple polyadenine (poly-A) chains. PHF-fixed poly-A chains then substantially boosted the localized concentration of CRISPR/Cas12a systems and vastly enhanced their efficacy in cleaving reporter nucleic acids. Our findings indicated that the spatial confinement effect facilitated by PHFs promoted frequent molecular collisions and accelerated multiple enzymatic reactions. The developed sensing strategy allows for the detection of PNK activity within a linear range of 0.001-1 U/mL, with a detection limit of 1.82 × 10^-4 U/mL. Additionally, this strategy has been successfully applied to detect PNK activity in cell extracts and to screen for PNK inhibitors. Owing to these advantages, PNK can be rapidly and accurately detected with a high sensitivity, specificity, and biostability.

News (Medical) associated with Uridine

10 Nov 2023

·synapse.patsnap.com

Latest Research Progress on TLR Adjuvants

The TLR agonists used in vaccine formulations come in various forms, ranging from lipopeptides to single-stranded DNA and RNA. Below, we will introduce the main categories of TLR adjuvants. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs, indications, organizations, clinical trials, clinical results, and drug patents related to this target. TLR2TLR2 is expressed on the surface of various cells, including monocytes, macrophages, endothelial cells, epithelial cells, natural killer cells, dendritic cells, myeloid-derived suppressor cells, platelets, and mast cells. The PAMP library recognized by TLR2 is the most extensive, as it can form heterodimers with TLR1 and TLR6 (and TLR10 in humans). The range of TLR2 adjuvants is extensive, including synthetic lipopeptides (PAM3CSK4 and PAM2CSK4), arabino-mannose lipids, phospholipidic acid, GPI membrane anchors, yeast polysaccharides, and peptidoglycans. Recent trends in TLR2 research include the discovery of small synthetic TLR2 agonists, improvements in the characteristics of traditional TLR2 agonists, and the bio-conjugation of TLR2 with vaccine antigens. For example, XS15 (PAM3CS-GDPKHPKSF) is a new TLR-1/2 agonist based on PAM3CS, where the four lysines (K4) of PAM3CSK4 are replaced with a nonapeptide (GDPKHPKSF) to alter the solubility of the conjugate, promoting uptake and facilitating purification. Constraints of using TLR2 agonists as adjuvants include the size, complexity, and hydrophobicity of most ligands. TLR3TLR3 is an intracellular recognition system that reacts to viral nucleic acids (dsRNA, ssRNA, and ssDNA) and endogenous double-stranded RNA. Many TLR3 agonists have been developed, such as RGC100 and ARNAX, a synthetic DNA-RNA hybrid compound. However, in the past two years, researchers have returned to using traditional dsRNA analog ligands, such as poly IC, focusing on improving their delivery modes and new disease applications. TLR4TLR4 is the most studied member of the TLR family, recognizing lipopolysaccharides (LPS). TLR4 is located on the cell membrane, mainly expressed on myeloid cells, but not on plasmacytoid dendritic cells (pDCs) and immature B cells. TLR4 recognizes LPS through its co-receptors myeloid differentiation factor-2 (MD-2) and CD14. Recent works on TLR4 agonists concentrate on the development and evaluation of modified products, such as monophosphoryl lipid A (MPLA) and Glucopyranosyl lipid A (GLA), which are structurally related to LPS, but have no high pyrogenicity while maintaining strong immunoenhancing characteristics, thus increasing their clinical feasibility. TLR5TLR5 recognizes flagellin protein and is expressed on epithelial cells and immune cells (such as macrophages and immature DC), generating immune responses through the MyD88-dependent signaling pathway. Recent work on TLR5 agonists has mainly focused on enhancing tolerance. Unfortunately, flagellin can induce unnecessary hyperreactivity, as a protein, it can induce antibodies against itself, interfering with its function as an adjuvant. This issue has been solved by research through removing the B cell epitope region from flagellin, the deimmunized flagellin retains its TLR5 adjuvant activity. TLR7/8TLR7 and TLR8 are located on the endosomal membrane of immune cells. TLR7 is primarily expressed in pDC and B cells, while TLR8 is expressed in myeloid dendritic cells and monocytes, with lower expression in pDC. TLR7/8 recognizes single-strand ribonucleic acid (ssRNA), and signals through the MyD88-dependent pathway. Among natural ligands, oligonucleotides (ORNs) enriched with adenine and uridine can activate TLR8 without any effect on TLR7. However, ORNs enriched in guanine activate TLR7 and TLR8-dependent signal transduction. TLR7 exists as a monomer and dimerizes in the presence of ligand, while TLR8 exists as weakly dimerized in its natural state and undergoes conformational change when ligand binds. To date, more than15 novel heterocyclic molecules, such as imidazoquinoline, oxazine, pyrimidine, pyridopyrimidine, pyrrolopyrimidine and benzimidazole, have been identified as TLR7/8 agonists. A common drawback of TLR7/8 agonists is their reactogenicity, and in recent years, numerous studies have attempted to overcome these adverse effects. Encapsulating TLR7/8 agonists in nanoparticles based on cationic DOEPC liposome formulations, or covalently linking these small molecules to hyperbranched polymers, can avoid their harmful systemic reactions while preserving their impact on humoral immunity. TLR9TLR9 is located within the endosomal membrane in cells, recognizing the single-stranded unmethylated CpG oligonucleotides of bacteria and virus DNA. TLR9 is expressed on immune cells such as dendritic cells, macrophages, natural killer cells, and other APCs. Synthetic CpG sequences can be used as TLR9 agonists to enhance the immune response of vaccines, and each unique sequence variant combination has been proven to have different structural and biological characteristics. The latest developments in TLR9 agonists in the past two years have mainly focused on the efficient delivery and uptake of CpG to cells. For example, one study introduced a new method of conjugating CpG-ODN to novel cationic liposomes, this compound can induce a strong immune response at low antigen and adjuvant doses. Combined TLR AdjuvantsCombining different TLR agonists in a single vaccine can generate a synergistic effect, driving potent vaccine immune responses. For example, liposomal adjuvants containing 1V270 (TLR7 agonist) and 2B182C (TLR4 agonist) induced balanced anti-HA and anti-NA IgG1 and IgG2a responses against influenza, without the overreactivity commonly associated with Th1 proinflammatory responses. Similarly, one study assessed the co-encapsulation of ovalbumin (OVA) with ten unique combinations of two to three TLR ligands, including Pam3CSK4 (TLR2 agonist), MPLA (TLR4 agonist), imiquimod (TLR7/8 agonist) and CpG (TLR9 agonist), with triple combinations promoting antigen-specific antibody titers through a balanced overall Th1/Th2 response. Therefore, combinations of TLR adjuvants can offer broad customizability of immune responses. Combinations of TLR agonists with other PAMPs such as NOD2 and macrophage-inducible Ca²⁺-dependent lectin receptor (Mincle) ligands are also promising. Covalent linkage of CL239 (TLR7 agonist) and muramyl dipeptide (NOD2 agonist), and incorporation of the dual agonist as nanoparticles with the NP-p24 HIV vaccine, synergistically enhanced protection in mice. SummarizeTLR agonists utilize endogenous innate immune pathways to enhance vaccine adaptive immune responses. Over the past two years, the domain of adjuvants has been primarily governed by research into the COVID-19 vaccine. The driving force of this pandemic has rapidly promoted the development of the adjuvant field, and several novel adjuvants have now been incorporated into licensed vaccines for COVID-19. Beyond COVID-19, the demand for more effective adjuvants continues to grow, particularly in the areas of difficult-to-prevent infectious diseases such as cancer, malaria, tuberculosis, and HIV. Unraveling the mechanisms behind the action of TLR co-adjuvants, coupled with increased safety and efficacy research data, can help drive the development of the next generation of adjuvant platforms.

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".

100 Deals associated with Uridine

External Link

KEGG	Wiki	ATC	Drug Bank
D00342	Uridine	-	DB02745

R&D Status

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

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


5288 (AAN2020)	Not Applicable	Epileptic encephalopathy	-	Uridine supplementation	ohnrwusfpt(qwyyadscfu) = qflbccktpq degllatwlf (pqhjqoapmn )	-	14 Apr 2020
ACTG 5229 \| A5229 (Pubmed \| AIDS)	Not Applicable	Lipodystrophy	165	NucleomaxX	rmagpmzrih(zmslixkeac) = gsuyyekfle vfxhuhrnoq (cjijiopbff )	-	23 Oct 2010
				Placebo	rmagpmzrih(zmslixkeac) = bgvqiwslvv vfxhuhrnoq (cjijiopbff )
IAS2009	Not Applicable	Lipodystrophy	45	Uridine	aozbmrcjpg(sgafhlrxvv) = horyobiukl uztrgcaqwz (pecfprffit ) View more	-	01 Jan 2009
				Pravastatin	aozbmrcjpg(sgafhlrxvv) = pjzzudkilh uztrgcaqwz (pecfprffit )
SFN2008	Not Applicable	Brain Injuries, Traumatic	-	Uridine 16mg/kg	eyrnnmpnuf(oodvoxcvxw) = wbaidcfqme xpyipvsvft (rqfthwsemw )	-	18 Nov 2008
				Uridine 32mg/kg	eyrnnmpnuf(oodvoxcvxw) = ahmxwfqhsm xpyipvsvft (rqfthwsemw )
EULAR2007	Not Applicable	Mitochondrial Myopathies	9	Mitocnol	kelkswyxis(woqlsbjsor) = xnajgjhpro hegvzgigel (jzzkrhvkvr ) View more	Positive	13 Jun 2007
				Zidovudine	kelkswyxis(woqlsbjsor) = ubhbxwiril hegvzgigel (jzzkrhvkvr ) View more
IAS2003	Not Applicable	-	-	Uridine	mhrlrglzmk(yejuszpffe) = fully restored szaabbmzur (xljbqkzaqq ) View more	-	01 Jan 2003

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