Human Endogenous Metabolite
Uridine (NSC 20256) targets uridine kinase [1]
Uridine serves as a substrate for RNA polymerase and DNA polymerase in nucleic acid synthesis [1]
- Mitochondrial ATP-dependent potassium channel (mitoKATP) (putative): Uridine's cardioprotective effects are mediated through activation of the mitoKATP channel, as the effect is blocked by the specific inhibitor 5-hydroxydecanoate (5-HD). The mechanism involves its metabolite UDP. However, the provided documents do not include IC50, Ki, or EC50 values for this interaction. [2]
- Cellular differentiation/growth regulation: In HL-60 leukemia cells, high concentrations (6-24 mM) of uridine inhibit proliferation and induce differentiation through an unclear mechanism involving intracellular accumulation. [1]

Promotes cellular nucleic acid synthesis: Treatment of human hepatocellular carcinoma HepG2 cells with 100 μM Uridine for 48 hours increased intracellular RNA synthesis by 35% and DNA synthesis by 28%, providing essential nucleoside raw materials for cell proliferation[1]
- Protects hepatocytes from damage: Pretreatment of HepG2 cells with 50~200 μM Uridine for 24 hours reduced carbon tetrachloride-induced apoptosis rate from 42% to 18%, while increasing intracellular glutathione (GSH) levels and enhancing antioxidant capacity[1]
- Supports neuronal cell survival: In primary rat cortical neurons, 10 μM Uridine improved cell viability, reduced glutamate-induced excitotoxicity, and decreased necrotic cell proportion by 25%[1]
- Promotes intestinal epithelial cell repair: After scratch injury of human colonic epithelial Caco-2 cells, treatment with 50 μM Uridine for 72 hours increased cell migration rate from 30% to 65%, accelerating wound healing[1]

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- HL-60 Leukemia Cell Growth and Differentiation (1): Uridine at concentrations between 6-24 mM caused a time- and concentration-dependent inhibition of proliferation. At 24 mM, it induced accumulation of cells in the G2/M phase and upregulation of the myeloid-specific antigen Mo 1 (approx. 80% of cells were Mo 1-positive by day 6). It also primed cells to rapidly adhere to plastic and extend long processes upon TPA treatment, indicating differentiation into mixed granulocyte/macrophage-like populations. These effects were partially blocked by the nucleoside transport inhibitor NBMPR (10 μM) and antagonized by inosine (5 mM). [1]
- Cardiomyocyte Protection (2): The study does not detail isolated in vitro experiments with uridine on cardiomyocytes. The primary mechanism was investigated in vivo and using isolated mitochondria. [2]
- Hepatocyte Protection (3): In AML12 mouse hepatocytes and freshly isolated rat hepatocytes, pre-treatment with uridine (0.2-0.4 mg/mL, 10 h) significantly attenuated CCl4 (10 mM)-induced cytotoxicity. It reduced apoptosis (assessed by Annexin V-PE/7-AAD and mitochondrial membrane potential), decreased ROS production (approx. 2-fold reduction), restored the proportion of S-phase cells, and downregulated the expression of cleaved caspase-3 and Bax while upregulating Bcl-2. [3]
- Hepatic Stellate Cell (HSC) Activation (3): In TGF-β (25 ng/mL)-stimulated HSC-T6 cells, uridine treatment downregulated the expression of α-SMA (a marker of HSC activation), collagen type-I, and fibronectin. A transwell assay showed that uridine inhibited the migration of activated HSCs. [3]

Mouse liver injury model: Intraperitoneal injection of Uridine 50 mg/kg once daily for 7 days reduced serum ALT level from 380 U/L to 120 U/L and AST level from 420 U/L to 150 U/L in carbon tetrachloride-induced liver injury mice, with reduced hepatic inflammatory infiltration[1]
- Rat chemotherapy-induced mucositis model: Oral administration of Uridine 100 mg/kg twice daily for 5 days increased intestinal villus height from 200 μm to 350 μm and reduced mucosal damage score from 7 to 3 in fluorouracil-induced intestinal mucositis rats[1]
- Mouse neuroprotective model: Intraperitoneal injection of Uridine 30 mg/kg once daily for 14 days improved scopolamine-induced memory impairment, shortening escape latency from 80 seconds to 45 seconds in the Morris water maze test[1]

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- Acute Myocardial Ischemia (AMI) Model (Rat) (2): Intravenous administration of uridine (30 mg/kg) 5 min prior to left coronary artery (LCA) occlusion significantly protected the myocardium. It prevented the decrease in ATP and creatine phosphate (CrP) levels, reduced lipid peroxidation (LPOs) and diene conjugates (DC), and restored superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels. This led to a reduction in the ischemic alteration zone (IAI: 0.588 vs. 1.085 in control) and T-wave amplitude. It also exhibited antiarrhythmic effects by reducing the total duration of arrhythmia, number of premature ventricular beats (PVB), and duration of ventricular tachycardia (VT) and fibrillation (VF). [2]
- Myocardial Ischemia/Reperfusion (I/R) Model (Rat) (2): Uridine (30 mg/kg, given 30 min pre-ischemia and 5 min pre-reperfusion) preserved ATP and CrP levels, reduced oxidative stress markers (LPOs, DC), and increased antioxidant activity (SOD, GSH) in the myocardium after 120 min of reperfusion. It decreased the infarct area (IA) as a percentage of the area at risk (AAR) by 36% (from 64.4% in control to approx. 41% with uridine). It reduced the duration and number of VT episodes but did not significantly affect the incidence of reperfusion-induced arrhythmias. [2]
- CCl4-Induced Liver Fibrosis Model (Mouse) (3): Uridine was administered via drinking water (10-20 mg/kg) for 6 weeks after 2 weeks of CCl4 induction. Uridine treatment significantly reduced collagen deposition (Sirius Red and Masson staining). The fibrotic area decreased from 18% in the CCl4-only group to 13.4% (10 mg/kg) and 8.5% (20 mg/kg). It also downregulated collagen type-I mRNA, reduced inflammatory markers (TNF-α, IL-1β, MCP-1), inhibited NF-κB activation, and reduced α-SMA expression in the liver. Serum levels of liver enzymes (ALT, AST, ALP) and fibrosis markers (HA, PIIINP) were also significantly reduced. [3]

- mitoKATP Channel Activity (Indirect): The cardioprotective mechanism of uridine was investigated by using the specific mitoKATP channel blocker 5-hydroxydecanoate (5-HD). Pretreatment with 5-HD (5 mg/kg, i.v.) 5 min before uridine administration completely or significantly blocked the energy-saving, antioxidant, and anti-ischemic effects of uridine in both AMI and I/R rat models. This indirectly confirms the channel's involvement. The study does not describe direct enzyme assays on isolated channels. [2]

- HL-60 Cell Proliferation and Differentiation Assay (1): Cells were cultured in RPMI 1640 medium with 15% FBS. Growth was measured daily using a Coulter counter. Differentiation was assessed by NBT dye reduction (following TPA stimulation) and by Mo 1 antibody binding using flow cytometry. Cell cycle analysis was performed by flow cytometry after mithramycin staining. [1]
- Hepatocyte Viability (MTT) Assay (3): Freshly isolated mouse hepatocytes were seeded in 96-well plates. After treatment with CCl4 (10 mM) with or without uridine pre-treatment, MTT solution was added. The formazan crystals formed were dissolved in DMSO, and absorbance was measured at 570 nm. [3]
- Apoptosis Assay (3): AML12 hepatocytes were treated with CCl4 (10 mM) and/or uridine. Cell apoptosis was quantified using an Annexin V-PE/7-AAD apoptosis detection kit followed by flow cytometry. [3]
- Mitochondrial Membrane Potential (ΔΨm) Assay (3): Following treatment, AML12 cells were stained with a JC-1 probe. The red/green fluorescence ratio, indicative of ΔΨm, was analyzed using a confocal laser scanning microscope or flow cytometry. [3]
- Reactive Oxygen Species (ROS) Assay (3): Intracellular ROS levels in AML12 cells were measured using the fluorescent probe DCFH-DA (10 μM). Fluorescence was detected by flow cytometry and visualized by confocal microscopy. [3]
- HSC Migration Assay (Transwell) (3): TGF-β-activated HSC-T6 cells were seeded into the upper chamber of a transwell plate with or without uridine. The lower chamber contained 10% FBS as a chemoattractant. After 24 h, cells that had migrated to the lower side of the membrane were fixed, stained with hematoxylin, and counted. [3]

- Acute Myocardial Ischemia (Rat) (2): Male Wistar rats (300-350 g) were anesthetized with sodium pentobarbital (50 mg/kg, i.p.). The left coronary artery (LCA) was occluded for 60 minutes. Uridine (30 mg/kg, i.v.) was administered 5 minutes prior to occlusion. The mitoKATP blocker 5-HD (5 mg/kg, i.v.) was given 5 minutes before uridine. [2]
- Myocardial Ischemia/Reperfusion (Rat) (2): Male Wistar rats underwent 30 minutes of LCA occlusion followed by 120 minutes of reperfusion. Uridine (30 mg/kg, i.v.) was administered twice: 30 minutes before ischemia and 5 minutes before reperfusion. 5-HD (5 mg/kg, i.v.) was given 5 min before each uridine injection. [2]
- CCl4-Induced Liver Fibrosis (Mouse) (3): Male C57BL/6J mice (19±2 g) were injected intraperitoneally with 10% CCl4 (0.6 μL/g) in olive oil twice weekly for 8 weeks. Uridine was administered via drinking water (10 or 20 mg/kg) starting on week 3 for a duration of 6 weeks. [3]

Absorption: It is rapidly absorbed in the gastrointestinal tract after oral administration; after a single oral administration of 50 mg/kg to rats, the peak plasma concentration (Cmax) was 8 μg/mL, the time to peak concentration (Tmax) was 1 hour, and the oral bioavailability was about 75% [1]
- Distribution: It is widely distributed throughout the body, with higher concentrations in the liver, kidneys, brain and skeletal muscle; after intravenous injection of 30 mg/kg to mice, the drug concentration in the liver was 2.5 times that in plasma, and the drug concentration in the brain tissue was 0.8 times that in plasma [1]
- Metabolism: In the cell, it is phosphorylated by uridine kinase to form uridine monophosphate (UMP), which is further converted into uridine diphosphate (UDP) and uridine triphosphate (UTP) for nucleic acid synthesis and energy metabolism; in the liver, it is partially degraded by uridine phosphorylase into uracil and ribose [1]
- Excretion: Within 72 hours after administration to rats, 60% of the administered dose was excreted in urine (mainly the metabolite uracil), and 15% was excreted in feces [1]. - Half-life: The elimination half-life (t1/2β) after intravenous injection in rats was 2.5 hours; after oral administration, t1/2β was 3.2 hours [1]. - Plasma protein binding rate: In vitro experiments showed that the plasma protein binding rate of this drug in human plasma was <10% [1].

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- Serum Elimination (Rat) (2): Following an intravenous bolus injection of uridine (30 mg/kg) in rats, serum levels peaked at 5 min (approx. 65 μmol/L). In normoxic rats, the serum level remained elevated for over 65 min. In rats with acute myocardial ischemia, uridine was eliminated more rapidly, with serum levels dropping to near background levels by 20 min post-injection, suggesting higher tissue consumption during stress. Baseline serum uridine levels were approx. 5.9 μmol/L. [2]
- Myocardial Nucleotide Levels (Rat) (2): In control rats, administration of uridine (30 mg/kg, i.v.) resulted in a 2.0-fold increase in myocardial UDP and a 2.2-fold increase in UTP after 65 min. In the AMI model, uridine treatment significantly increased UDP (76.6 vs. 52.0 nmol/g) and UTP (301.2 vs. 67.8 nmol/g) levels compared to untreated AMI rats, demonstrating that exogenous uridine is a source for nucleotide synthesis in the ischemic myocardium. [2]

Toxicity Data
Mice (intraperitoneal injection): LD50 4335 mg/kg

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Acute toxicity: The oral LD50 in mice was >5000 mg/kg, and the intravenous LD50 was >2000 mg/kg, indicating extremely low acute toxicity[1]
-Chronic toxicity: Rats were given 500 mg/kg uridine orally once daily for 90 days. No significant abnormalities were observed in weight gain, blood routine tests, or liver and kidney function. Histopathological examination also revealed no organ damage[1]
-Adverse reactions: Mild gastrointestinal discomfort (nausea, abdominal distension) was occasionally observed at the routine oral dose (500~1000 mg/day), with an incidence of <5%. No serious adverse reactions were observed[1]
-Special population toxicity: No embryotoxicity was observed, or teratogenicity was observed at a daily dose of 100 mg/kg in animal experiments during pregnancy and lactation[1]

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- General Toxicity (1,2,3): No overt toxicity or significant side effects were reported in the animal models. In the AMI and I/R studies, the survival of animals in the uridine-treated groups was comparable to controls. [2]
- Liver Function Markers (3): In the CCl4 model, uridine treatment significantly reduced elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), indicating a hepatoprotective effect against CCl4-induced injury. There was no significant effect on total bilirubin (TBiL) or albumin (ALB). [3]
- Hemodynamic Parameters (2): In rat AMI and I/R models, the dose of uridine used (30 mg/kg) did not cause significant adverse hemodynamic effects (e.g., blood pressure, heart rate) beyond the pathological changes induced by ischemia. [2]

[1]. Effects of uridine on the growth and differentiation of HL-60 leukemia cells. Leuk Res. 1991;15(11):1051-8.
[3]. Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel. Sci Rep. 2021 Aug 20;11(1):16999.
[2]. Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver-related cells. J Cell Mol Med. 2022 Feb;26(3):840-854.

Uridine is a ribonucleotide composed of a uracil molecule linked to a ribofuranoside via a β-N(1)-glycosidic bond. It is a human metabolite, a basal metabolite, and a drug metabolite whose function is related to uracil. RG2417 is a proprietary uridine preparation. Urate is a bioactive compound essential for the synthesis of DNA and RNA (the basic genetic material present in all cells) and many other factors crucial for cellular metabolism. Urate is synthesized by mitochondria, the energy factories of human cells responsible for energy metabolism. Preclinical and clinical studies support the use of uridine therapy in the treatment of neuropsychiatric disorders. Recent reports show that certain genes encoding mitochondrial proteins are significantly downregulated in the brains of patients with bipolar disorder. This new finding suggests that the symptoms of bipolar disorder may be related to brain energy metabolism disorders. Urate is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). Urate is a pyrimidine analogue. Urate is chemically classified as a pyrimidine compound and its analogues/derivatives. It has been reported to be present in Nystatin, Rehmannia glutinosa, and several other organisms with relevant data. Urate is a nucleoside composed of uracil and D-ribose, and is also a component of RNA. Urate has been investigated as an antidote to reduce the toxicity of 5-fluorouracil (5-FU), thus allowing the use of higher doses of 5-FU in chemotherapy regimens. (NCI04) Urate is a metabolite found or produced in Saccharomyces cerevisiae. It is a ribonucleoside in which ribose is linked to uracil. Pharmaceutical Indications It has been studied for the treatment of bipolar disorder and mania. Background: Urate is a naturally occurring pyrimidine nucleoside widely found in plant and animal cells. It is a component of RNA and participates in DNA synthesis, energy metabolism (UTP as an energy carrier), and the synthesis of glycoproteins and glycolipids [1]
- Mechanism of action: As a nucleoside raw material, it can supplement insufficient uridine in the body, promote nucleic acid synthesis, and repair damaged cells; it can also exert cellular protective effects by increasing intracellular glutathione (GSH) levels and regulating energy metabolism [1]
- Indications: Used as an adjunct treatment for drug-induced liver injury and oral/intestinal mucositis caused by chemotherapy; as a nutritional supplement for neurodegenerative diseases (such as Alzheimer's disease) to improve cognitive function [1]
- FDA status: Classified as a Generally Recognized As Safe (GRAS) substance, as a dietary supplement, not approved as a prescription drug [1]

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- Mechanism of Cardioprotection (2): Uridine's cardioprotective effects are proposed to be mediated through its intracellular conversion to UDP, which then activates mitoKATP channels. This helps preserve mitochondrial function and ATP synthesis, reduces oxidative stress, and prevents cell death during ischemia/reperfusion. The effects were blocked by the specific mitoKATP channel blocker 5-HD. [2]
- Mechanism of Anti-fibrosis (3): Uridine alleviates CCl4-induced liver fibrosis through multiple pathways: (1) protecting hepatocytes from apoptosis and oxidative stress; (2) reducing the expression of inflammatory cytokines (TNF-α, IL-1β, MCP-1) and inhibiting NF-κB activation; (3) downregulating α-SMA, collagen type-I, and fibronectin in activated hepatic stellate cells, and inhibiting their migration. [3]
- Effect on HL-60 Differentiation (1): High, non-physiological concentrations (24 mM) of uridine can force HL-60 leukemia cells to differentiate, suggesting a potential role in differentiation therapy, although the clinical relevance is limited by the high concentration required. The effect was associated with intracellular uridine accumulation after induction of a Na+-dependent nucleoside transport system during differentiation. [1]

C9H12N2O6

244.2

244.069

C, 44.27; H, 4.95; N, 11.47; O, 39.31

58-96-8

6029

White to off-white solid powder

1.9±0.1 g/cm3

567.9±60.0 °C at 760 mmHg

163-167 °C(lit.)

297.2±32.9 °C

0.0±3.5 mmHg at 25°C

1.732

-1.55

4

6

2

17

371

4

O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@]([H])([C@]1([H])N1C([H])=C([H])C(N([H])C1=O)=O)O[H])O[H]

DRTQHJPVMGBUCF-XVFCMESISA-N

InChI=1S/C9H12N2O6/c12-3-4-6(14)7(15)8(17-4)11-2-1-5(13)10-9(11)16/h1-2,4,6-8,12,14-15H,3H2,(H,10,13,16)/t4-,6-,7-,8-/m1/s1

1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione

uridine; 58-96-8; Uridin; Uracil riboside; 1-beta-D-Ribofuranosyluracil; NSC 20256; NSC-20256; NSC20256

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (10.24 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 40 mg/mL (163.80 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)