Hildyard, John C. W.’s team published research in Biochimica et Biophysica Acta, Bioenergetics in 1707 | CAS: 853953-65-8

Hildyard, John C. W. published the artcileIdentification and characterization of a new class of highly specific and potent inhibitors of the mitochondrial pyruvate carrier, COA of Formula: C21H18FN5O5S, the publication is Biochimica et Biophysica Acta, Bioenergetics (2005), 1707(2-3), 221-230, database is CAplus and MEDLINE.

Two novel thiazolidine compounds, GW604714X and GW450863X, were found to be potent inhibitors of mitochondrial respiration supported by pyruvate but not other substrates. Direct measurement of pyruvate transport into rat liver and yeast mitochondria confirmed that these agents inhibited the mitochondrial pyruvate carrier (MPC) with K_i values <0.1 μM. Inhibitor titrations of pyruvate-dependent respiration by heart mitochondria gave values (±S.E.) for the concentration of inhibitor binding sites (pmol per mg protein) and their K_i (nM) of 56.0±0.9 and 0.057±0.010 nM for the more hydrophobic GW604714X; for GW450863X the values were 59.9±4.6 and 0.60±0.12 nM. [³H]-methoxy-GW450863X binding was also used to determine the MPC content of the heart, kidney, liver and brain mitochondria giving values of 56, 40, 26 and 20 pmol per mg protein resp. Binding to yeast mitochondria was <10% of that in rat liver mitochondria, consistent with the slow rate of pyruvate transport into yeast mitochondria. [³H]-methoxy-GW450863X binding was inhibited by GW604714X and by the established MPC inhibitor, UK5099. The absorbance spectra of GW450863X and GW604714X were markedly changed by the addition of β-mercaptoethanol suggesting that the novel inhibitors, like α-cyanocinnamate, possess an activated double bond that attacks a critical cysteine residue on the MPC. However, no labeled protein was detected following SDS-PAGE suggesting that the covalent modification is reversible. GW604714X and GW450863X inhibited L-lactate transport by the plasma membrane monocarboxylate transporter MCT1, but at concentrations more than four orders of magnitude greater than the MPC.

Biochimica et Biophysica Acta, Bioenergetics published new progress about 853953-65-8. 853953-65-8 belongs to thiazolidine, auxiliary class Metabolic Enzyme,MPC, name is 5-(5-(6-(4-Acetylpiperazin-1-yl)-3-nitropyridin-2-yl)-2-fluorobenzylidene)thiazolidine-2,4-dione, and the molecular formula is C21H18FN5O5S, COA of Formula: C21H18FN5O5S.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com