Merck, 5336600001, Lactate Dehydrogenase Inhibitor II, GSK2837808A

General description
A cell-permeable quinolinesulfonamide compound that acts as potent and reversible inhibitor of lactate dehydrogenase A (IC₅₀ = 2.6 nM for human LDH-A). The inhibition appears to be competitive with respect to NADH and non-competitive with respect to pyruvate. Exhibits high selectivity over LDH-B (IC₅₀ = 43 nM) and does not affect the activity of 32 other enzymes, receptors, and ion-channels even at high concentration (~ 10 µM). Rapidly reduces lactate production in hepatocellular (EC₅₀ = 400 and 588 nM in Snu398 and HepG2 cells, respectively) and breast carcinoma cell lines, and induces PKM2 activation (EC₅₀ = 600 nM in Snu398 cells). Shown to increase mitochondrial oxygen consumption rate (EC₅₀ = 500 and 900 nM in Snu398 and HepG2 cells, respectively) and causes a diminution in extracellular acidification rates (EC₅₀ = 600 nM in both cell lines). Shown to downregulate the ability of A549 cells to form tumorspheres and diminishes the number of CD24/CD44-positive cells in HMLER system and in stem cells isolated from HMLER. Blocks the proliferation of Snu398 cells and induces apoptosis within 24 h of incubation.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
lactate dehydrogenase A
Reversible: yes
Target IC₅₀: 2.6 nM for human LDH-A
Packaging
Packaged under inert gas
Other Notes
Xie, H. 2014. Cell Metab.19, 795.
Billiard, J. 2013. Cancer Metab.1, 19.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)