Category: 459420-09-8

Hanaoka, Kenjiro published the artcileDiscovery and Mechanistic Characterization of Selective Inhibitors of H₂S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide, Safety of 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one, the publication is Scientific Reports (2017), 40227, database is CAplus and MEDLINE.

Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiol. processes previously considered to be regulated by hydrogen sulfide (H₂S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H₂S-producing enzymes, was also recently shown to produce sulfane sulfur (H₂S_n). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chem. library (174,118 compounds) with our H₂S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H₂S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theor. calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the pos. charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the exptl. support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism.

Scientific Reports published new progress about 459420-09-8. 459420-09-8 belongs to pyrimidines, auxiliary class Metabolic Enzyme,3MST, name is 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one, and the molecular formula is C17H14N2O2S, Safety of 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Augsburger, Fiona published the artcileRole of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation, migration, and bioenergetics in murine colon cancer cells, Category: pyrimidines, the publication is Biomolecules (2020), 10(3), 447, database is CAplus and MEDLINE.

The current study was designed to investigate the functional role of 3-MST’s catalytic activity in the murine colon cancer cell line CT26. The novel pharmacol. 3-MST inhibitor HMPSNE was used to assess cancer cell proliferation, migration and bioenergetics in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux anal.). 3-MST expression was detected by Western blotting; H₂S production was measured by the fluorescent dye AzMC. The results show that CT26 cells express 3-MST protein and mRNA, as well as several enzymes involved in H₂S degradation (TST, ETHE1). HMPSNE exerted a bell-shaped effect on several cellular bioenergetic parameters related to oxidative phosphorylation, while other bioenergeticparameterswereeitherunaffectedorinhibitedatthehighestconcentrationoftheinhibitor tested (300μM). In contrast to 3-MST, the expression of CBS (another H₂S producing enzyme which has been previously implicated in the regulation of various biol. parameters in other tumor cells) was not detectable in CT26 cells and pharmacol. inhibition of CBS exerted no significant effects on CT26 proliferation or bioenergetics. In summary, 3-MST catalytic activity significantly contributes to the regulation of cellular proliferation, migration and bioenergetics in CT26 murine colon cancer cells.

Biomolecules published new progress about 459420-09-8. 459420-09-8 belongs to pyrimidines, auxiliary class Metabolic Enzyme,3MST, name is 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one, and the molecular formula is C17H14N2O2S, Category: pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia