LACTATE DEHYDROGENASE INHIBITOR II GSK2837808A (C15-1305-137)

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

Warning

Toxicity: Standard Handling (A)

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

Molecular Weight: 649.62. Empirical Formula: C₃₁H₂₅F₂N₅O₇S. Assay: ≥. 95% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: yellow. solubility: DMSO: 50 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.