2'-Deoxycytidine, a deoxynucleoside, inhibits the bioactivity of Brdu. 英译中： On Nov. 3, 2025, UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that KYGEVVI™ has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of adults and pediatric patients living with thymidine kinase 2 deficiency (TK2d), with an age of symptom onset on or before 12 years. It is the first and only approved treatment for these patients living with TK2d. TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive (worsening over time) and severe muscle weakness (myopathy) with no approved treatment options beyond supportive care until now. It is often fatal, with those experiencing initial symptoms on or before the age of 12 years facing a high risk of premature death (often occurring within 3 years after symptom onset). It is estimated that the worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people

Physicochemical Properties

Molecular Formula	C9H13N3O4
Molecular Weight	227.22
Exact Mass	227.09
Elemental Analysis	C, 47.57; H, 5.77; N, 18.49; O, 28.16
CAS #	951-77-9
Related CAS #	3992-42-5 (HCl);951-77-9;
PubChem CID	13711
Appearance	White to off-white solid powder
Density	1.7±0.1 g/cm3
Boiling Point	482.1±55.0 °C at 760 mmHg
Melting Point	209-211 °C(lit.)
Flash Point	245.4±31.5 °C
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.720
LogP	-1.73
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	16
Complexity	355
Defined Atom Stereocenter Count	3
SMILES	C1[C@@H]([C@H](O[C@H]1N2C=CC(=NC2=O)N)CO)O
InChi Key	CKTSBUTUHBMZGZ-SHYZEUOFSA-N
InChi Code	InChI=1S/C9H13N3O4/c10-7-1-2-12(9(15)11-7)8-3-5(14)6(4-13)16-8/h1-2,5-6,8,13-14H,3-4H2,(H2,10,11,15)/t5-,6+,8+/m0/s1
Chemical Name	4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
Synonyms	Cytosine; Doxecitine; Deoxycytidine; SR-13668; Desoxycytidin; Cytosine deoxyriboside; SR13668; Deoxyribose cytidine; SR 13668; deoxyriboside; 2'-deoxycytidine; 951-77-9; deoxycytidine; CYTIDINE, 2'-DEOXY-; dCYD; Desoxycytidin
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Brdu; PI3K/Akt; Endogenous Metabolite; Microbial Metabolite
ln Vitro	The progressive, often fatal myopathy seen in Thymidine Kinase 2 deficiency (TK2d) is caused by mutations in the nuclear TK2 gene, leading to a dysfunctional or deficient mitochondrial TK2 enzyme. This enzyme is essential for phosphorylating the pyrimidine nucleosides doxecitine (dC) and thymidine (dT) into dCMP and dTMP, which are precursors for the deoxyribonucleotide triphosphates (dNTPs) required for mitochondrial DNA (mtDNA) maintenance and replication. The resulting metabolic block causes severe mtDNA depletion and dysfunction of the mitochondrial respiratory chain.[] Doxecitine, in combination with doxribtimine, functions as a nucleoside substrate enhancement therapy that successfully bypasses the defective mitochondrial pathway. The high concentrations of exogenous dC and dT are primarily phosphorylated by intact cytosolic salvage enzymes, specifically Deoxycytidine Kinase (dCK) and Thymidine Kinase 1 (TK1). The nucleosides are actively transported into cells and across the blood-brain barrier via equilibrative nucleoside transporters. The resulting phosphorylated dNTP precursors are then made available to the mitochondria. This replenishes the critically depleted dNTP pools, which facilitates the replication of mtDNA by the mitochondrial DNA Polymerase gamma.
ln Vivo	Doxecitine's primary action is a substrate enhancement therapy that corrects the nucleoside imbalance caused by TK2d deficiency. The goal is to provide a high systemic concentration of deoxycytidine and deoxythymidine that can be utilized by unaffected salvage pathways. This action restores the synthesis of mitochondrial DNA (mtDNA) precursors, leading to the restoration of mtDNA copy number and subsequent improvement in respiratory chain enzyme (RCE) activities in affected tissues. This systemic correction counteracts the relentless muscle weakness and respiratory failure characteristic of TK2d, resulting in the amelioration of myopathy, delay of disease onset, and significantly prolonged survival in both preclinical models and patients.
ADME/Pharmacokinetics	Absorption Doxecitine is administered orally, with rapid absorption and plasma concentrations returning to near baseline within 8 to 12 hours. The absolute bioavailability of doxecitine following oral administration has not been determined. The median time to peak plasma concentration (Tmax) was approximately two hours for doxecitine. Route of Elimination Urinary excretion of intact doxecitine and doxribtimine was <1% of the dose in healthy subjects following an oral administration of doxecitine and doxribtimine. Protein Binding In vitro plasma protein binding of doxecitine was less than 10% over the concentration range between 0.23 mcg/mL and 23 mcg/mL. Metabolism / Metabolites Doxecitine is primarily degraded by cytidine deaminase to its nucleobases and the 2-deoxy-α-D-ribose 1-phosphate moiety. Intermediate products of doxecitine catabolism are deoxyuridine, uracil, and dihydrouracil with the end products β-alanine, ammonia, and carbon dioxide (CO2). Biological Half-Life The mean half-life was approximately 1 hour for doxecitine following a single oral administration of 133 mg/kg doxecitine under fed conditions in healthy adult subjects.
Toxicity/Toxicokinetics	About KYGEVVI KYGEVVI is a combination of doxecitine and doxribtimine, both pyrimidine nucleosides, indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years. Administration of KYGEVVI is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial DNA.1 This action restores mitochondrial DNA copy number in TK2d mutant mice. Important safety information for KYGEVVI1 Increase in Liver Transaminases Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI. If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated. Gastrointestinal Adverse Reactions Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with KYGEVVI. Based on the severity of the diarrhea and/or vomiting, reduce the dosage of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider restarting KYGEVVI at the last tolerated dose, and increase the dose as tolerated. For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently and provide supportive care with electrolyte repletion as clinically indicated.
References	[1]. Inhibition of biological effects of bromodeoxyuridine by deoxycytidine: correlation with decreased incorporation of bromodeoxyuridine into DNA. Somatic Cell Genet. 1976 Sep;2(5):469-81. [2]. Intravenously administered 2'-deoxycytidine suppresses mouse myeloma tumor growth. Biol Pharm Bull. 2012;35(2):251-5.
Additional Infomation	2'-deoxycytidine is a pyrimidine 2'-deoxyribonucleoside having cytosine as the nucleobase. It has a role as a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is functionally related to a cytosine. Deoxycytidine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). 2'-Deoxycytidine has been reported in Homo sapiens, Isodictya erinacea, and other organisms with data available. Doxecitine is a nucleoside component of DNA, composed of cytosine and deoxyribose, with chemopreventive activity. 2'-Deoxycytidine is a metabolite found in or produced by Saccharomyces cerevisiae. A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~220.05 mM) H2O : ~50 mg/mL (~220.05 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.00 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (11.00 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. Solubility in Formulation 4: 110 mg/mL (484.11 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.4010 mL	22.0051 mL	44.0102 mL
	5 mM	0.8802 mL	4.4010 mL	8.8020 mL
	10 mM	0.4401 mL	2.2005 mL	4.4010 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.