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.

Novel chiral Schiff base ligands (R)/(S)-2-amino-3-(((1-hydroxypropan-2-yl)imino)methyl)-4H-chromen-4-one (L(1) and L(2)) derived from 2-amino-3-formylchromone and (R/S)-2-amino-1-propanol and their Cu(II)/Zn(II) complexes (R1, S1, R2, and S2) were synthesized. The complexes were characterized by elemental analysis, infrared (IR), hydrogen ((1) H) and carbon ((13)C) nuclear magnetic resonance (NMR), electrospray ionization-mass spectra (ESI-MS), and molar conductance measurements. The DNA binding studies of the complexes with calf thymus were carried out by employing different biophysical methods and molecular docking studies that revealed that complexes R1 and S1 prefers the guanine-cytosine-rich region, whereas R2 and prefers the adenine-thymine residues in the major groove of DNA. The relative trend in K(b) values followed the order R1>S1>R2>S2. This observation together with the findings of circular dichroic and fluorescence studies revealed maximal potential of (R)-enantiomeric form of complexes to bind DNA. Furthermore, the absorption studies with mononucleotides were also monitored to examine the base-specific interactions of the complexes that revealed a higher propensity of Cu(II) complexes for guanosine-5'-monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine-5'-monophosphate disodium salt. The cleavage activity of R1 and R2 with pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage ability. Topoisomerase II inhibitory activity of complex R1 revealed that the complex inhibits topoisomerase II catalytic activity at a very low concentration (25 μM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin. Mohd Afzal Chirality . 2012 Dec;24(12):977-86.

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- Mechanism of action：dTMP is a key precursor of DNA synthesis, which is generated by the catalysis of thymidine kinase through the salvage - synthesis pathway. TK2 deficiency leads to dTMP deficiency, and the supplementation of deoxythymidine can be converted into dTMP to maintain mitochondrial DNA synthesis. [3]
- Indications：It is 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.

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