ANX-510 - CAS 3432-99-3
Catalog number: 3432-99-3
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
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ANX-510 is a folate-based biomodulator with potential antineoplastic activity. 5,10-methylenetetrahydrofolate (MTHF) stabilizes the covalent binding of the fluorouracil metabolite 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP) to its target enzyme, thymidylate synthase, which results in inhibition of thymidylate synthase, depletion of thymidine triphosphate (TTP), a necessary constituent of DNA, and tumor cell death.
5,10-methylenetetrahydrofolate; 5,10-Methylene-5,6,7,8-tetrahydrofolate; 5,10-MTHF; MTHF.
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Adventrx Pharmaceuticals Inc
1.Genetic polymorphisms and folate status.
Hiraoka M;Kagawa Y Congenit Anom (Kyoto). 2017 Sep;57(5):142-149. doi: 10.1111/cga.12232. Epub 2017 Jul 20.
Moderate hyperhomocysteinemia-induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one-carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10-methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status.
2.Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2.
Delk AS;Nagle DP Jr;Rabinowitz JC J Biol Chem. 1980 May 25;255(10):4387-90.
The methyl carbon of ribothymidine in Loop IV of the tRNA of Streptococcus faecalis, Bacillus subtilis, and some other microorganisms is derived directly from 5,10-methylenetetrahydrofolate, not S-adenosylmethionine. The pure enzyme from S. faecalis also requires FADH2. We have obtained evidence that tetrahydrofolate is a product of the reaction and demonstrated that label from [5-3H]5-deazaFMNH2 is incorporated into the methyl moiety of ribothymidine. These data indicate that the enzyme uses methylenetetrahydrofolate solely as a 1-carbon donor and employs FADH2 as a reducing agent in vitro according to the following reaction: tRNA(U psi C) + CH2 = THF + FADH2 leads to tRNA(T psi C) + THF + FAD.
3.Direct transfer of one-carbon units in the transformylations of de novo purine biosynthesis.
Smith GK;Mueller WT;Slieker LJ;DeBrosse CW;Benkovic SJ Biochemistry. 1982 Jun 8;21(12):2870-4.
It is shown that the transfer of formyl units in the de novo purine biosynthetic pathway as catalyzed by glycinamide ribonucleotide (GAR) transformylase and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase probably proceeds through a direct displacement mechanism involving only formyl donor (10-CHO-H4folate) and formyl acceptor (GAR or AICAR). The inability to observe enzyme-catalyzed solvent oxygen incorporation or uncoupling by hydroxylamine of 1:1 stoichiometry between formylated acceptor [formylglycinamide ribonucleotide or 5-(formylamino)imidazole-4-carboxamide ribonucleotide] and deformylated donor implies the absence of an amidine intermediate and suggests that either a formylated enzyme-bound intermediate is not formed or such an intermediate is not accessible to hydroxylamine.
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CAS 3432-99-3 ANX-510

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