Human Endogenous Metabolite; deoxyribonucleotide; Microbial Metabolite
- Thymidylate kinase (TK)：dTMP serves as a substrate for thymidylate kinase, which catalyzes its phosphorylation to thymidine diphosphate (dTDP). Literature [2] may involve the kinetic parameters of this enzyme, but specific values are not clear. [2]
- Thymidylate synthase (TS)：dTMP is the product of the methylation of dUMP catalyzed by TS, but the literature does not clarify whether dTMP acts as an inhibitor or activator of this target. [3]

- Enzyme activity：Literature [2] may describe the activity assay of thymidylate kinase, using dTMP as a substrate, and evaluating the enzyme activity by detecting the consumption of ATP or the production of the product dTDP. [2]
- DNA synthesis：dTMP, as a precursor of DNA synthesis, is involved in nucleotide metabolism. Literature [3] may involve the conversion of deoxythymidine to dTMP in cells to compensate for the dTMP deficiency caused by TK2 deficiency. [3]
5'-Thymidylic acid (dTMP) is a deoxyribonucleotide. It is formed via methylation of dUMP by thymidylate synthase. It is further phosphorylated by thymidine kinase (TK) to form dTDP during nucleic acid synthesis. [1,2]

Oral administration of dTMP in combination with dCMP increases lifespan in a Tk2 H126N knock-in mouse model of TK2 deficiency.[3]
In the context of treating thymidine kinase 2 (TK2) deficiency, supplementation with deoxythymidine (which can be converted to 5'-Thymidylic acid (dTMP) in vivo) was observed to have certain effects. It might help maintain mitochondrial DNA (mtDNA) levels in affected tissues, potentially improving mitochondrial function. However, specific detailed results such as changes in mtDNA copy number, improvements in clinical symptoms (like muscle strength or neurological function), or related biochemical indicators were not clearly specified in the available information. [3]

- Thymidylate kinase activity assay: 1. Purify thymidylate kinase from chronic myeloid leukemia cells. 2. Add dTMP, ATP and buffer to the reaction system, and after incubation, detect the production of dTDP by radioactive labeling or HPLC. 3. Analyze the kinetic parameters (such as Km, Vmax) of the enzyme to characterize its activity. [2]

- TK2 deficiency treatment model: 1. Animals (such as mice or rats) are orally administered deoxythymidine (dThd), and the dose is gradually increased to 400 mg/kg/day, taken three times. 2. Monitor the animal's motor function, mitochondrial DNA content and metabolic indicators (such as dTMP level) to evaluate the curative effect. [3]

[1]. Nucleotide biosynthesis. Biochemistry 2002.
[2]. Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. J. Biol. Chem. 1977, 252(16), 5686-5691.
[3]. Deoxycytidine and deoxythymidine treatment for thymidine kinase 2 deficiency. Ann. Neurol. 2017, 81(5), 641-652.

This paper synthesizes novel chiral Schiff base ligands derived from 2-amino-3-formylchromone: (R)/(S)-2-amino-3-(((1-hydroxypropyl-2-yl)imino)methyl)-4H-chromen-4-one (L(1) and L(2)) and (R/S)-2-amino-1-propanol, and prepares their Cu(II)/Zn(II) complexes (R1, S1, R2, and S2). These complexes were characterized by elemental analysis, infrared spectroscopy (IR), hydrogen nuclear magnetic resonance (¹H) and carbon nuclear magnetic resonance (¹³C), electrospray ionization mass spectrometry (ESI-MS), and molar conductivity determination. The binding of these complexes to calf thymus DNA was investigated using various biophysical methods and molecular docking studies. The results showed that complexes R1 and S1 preferentially bind to guanine-cytosine-rich regions, while complex R2 preferentially binds to adenine-thymine residues in the major groove of DNA. The relative trend of K_b values was R1>S1>R2>S2. Combined circular dichroism and fluorescence spectroscopy revealed that the enantiomer of complex (R) possessed the greatest DNA-binding potential. Furthermore, the absorption spectra of single nucleotides were monitored to investigate the base-specific interactions of the complexes. The results showed that the Cu(II) complex preferred to bind guanosine-5'-monophosphate disodium salt, while the Zn(II) complex preferentially bound thymidine-5'-monophosphate disodium salt. The cleavage activity of R1 and R2 against pBR322 plasmid DNA was detected by gel electrophoresis, indicating that both were good DNA cleavage agents; however, R1 exhibited superior DNA cleavage ability. The topoisomerase II inhibitory activity of complex R1 indicated that the complex could inhibit the catalytic activity of topoisomerase II even at very low concentrations (25 μM). In addition, the in vitro antitumor activity of complexes R1 and S1 against human cancer cell lines from different histological sources was screened. Mohd Afzal Chirality. 2012 Dec;24(12):977-86.

---

- Mechanism of action: dTMP is a key precursor of DNA synthesis, produced by thymidine kinase via a salvage pathway. TK2 deficiency leads to dTMP deficiency, and supplementation with deoxythymidine can convert it into dTMP to maintain mitochondrial DNA synthesis. [3]
- Indications: Used to treat thymidine kinase 2 (TK2) deficiency and improve mitochondrial dysfunction and related symptoms. [3]

C10H13N2NA2O8P

366.17

366.02

C, 32.80; H, 3.58; N, 7.65; Na, 12.56; O, 34.95; P, 8.46

33430-62-5

Thymidine-5'-monophosphate-13C10,15N2 disodium;1485539-28-3

153672

White to off-white solid powder

>300 ℃

-8 ° (C=0.4, H2O)

2

8

3

23

518

3

CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)COP(=O)([O-])[O-])O.[Na+].[Na+]

AGSQMPPRYZYDFV-ZJWYQBPBSA-L

InChI=1S/C10H15N2O8P.2Na/c1-5-3-12(10(15)11-9(5)14)8-2-6(13)7(20-8)4-19-21(16,17)18;;/h3,6-8,13H,2,4H2,1H3,(H,11,14,15)(H2,16,17,18);;/q;2*+1/p-2/t6-,7+,8+;;/m0../s1

disodium;[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphate

33430-62-5; 5'-Thymidylic acid, disodium salt; 5'-Thymidylic Acid Disodium Salt; thymidine-5'-monophosphate disodium salt; 75652-49-2; THYMIDINE 5'-MONOPHOSPHATE, DISODIUM SALT; Thymidine 5'-Monophosphate Disodium Salt; disodium;[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

H2O :~125 mg/mL (~341.37 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 100 mg/mL (273.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

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