A cell-permeable quinoline-sulfonamide that acts as a potent allosteric PKM2 activator both in cell-free enzymatic assays (AC50 = 17nM with 40ng PKM2/200ul) and in cultures (AC50 = 45nM in A549 cells) via a high affinity, 2:1 stoichiometric binding, effectively locking PKM2 in an active tetrameric state resistant to known intracellular negative regulators of FBP-activated PKM2 tetramer. PKM2 stimulation by compound treatment is shown to result in decreased serine biosynthesis (by 56%; 500nM for 24h) with concomitant increase in serine influx as a compensating mechanism for maintaining cellular serine level necessary for supporting A549 proliferation. Simultaneous PKM2 activation and culture serine withdrawal results in cytostatic A549 growth arrest, but not apoptosis.
Synonyms:Pyruvate Kinase M2 Activator III, N-(4-(4-(2-Methoxyphenyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide
Formula:C27H26N4O4S
Solubility:DMSO
Primary Target:PKM2
Storage and Stability:May be stored at 4°C. For long-term storage, aliquot and store at 4°C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.
