Zhu, Hu published the artcileIdentification of Activators of Human Fumarate Hydratase by Quantitative High-Throughput Screening, Safety of (S)-2-hydroxysuccinic acid, the main research area is fumarate hydratase antioxidant hereditary leiomyomatosis renal cell cancer; automation; enzyme assays; enzyme kinetics; fluorescence methods; robotics; ultra-high-throughput screening.
Fumarate hydratase (FH) is a metabolic enzyme that is part of the Krebs cycle and reversibly catalyzes the hydration of fumarate to malate. Mutations of the FH gene have been associated with fumarate hydratase deficiency (FHD), hereditary leiomyomatosis and renal cell cancer (HLRCC), and other diseases. Currently, there are no high-quality small-mol. probes for studying human FH. To address this, we developed a quant. high-throughput screening (qHTS) FH assay and screened a total of 57,037 compounds from inhouse libraries in dose-response. While no inhibitors of FH were confirmed, a series of phenyl-pyrrolo-pyrimidine-diones were identified as activators of human FH. These compounds were not substrates of FH, were inactive in a malate dehydrogenase counterscreen, and showed no detectable reduction-oxidation activity. The binding of two compounds from the series to human FH was confirmed by microscale thermophoresis. The low hit rate in this screening campaign confirmed that FH is a “”tough target”” to modulate, and the small-mol. activators of human FH reported here may serve as a starting point for further optimization and development into cellular probes of human FH and potential drug candidates.
SLAS Discovery published new progress about Enzyme kinetics. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Safety of (S)-2-hydroxysuccinic acid.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts