PKM2 Activator III-Calbiochem

C₂₇H₂₆N₄O₄S

502.58

A cell-permeable quinoline-sulfonamide that acts as a potent allosteric PKM2 activator both in cell-free enzymatic assays (AC₅₀ = 17 nM with 40 ng recombinant PKM2/200 µL) and in cultures (AC₅₀ = 45 nM in A549 cells) via a high affinity (no dissociation in >1.5 h), 2:1 (compound to PKM2 tetramer) stoichiometric binding, effectively locking PKM2 in an active tetrameric state that is resistant to known intracellular negative regulators of PKM2 tetramer induced by the natural activator FBP (fructose 1,6-bisphosphate). PKM2 stimulation by compound treatment is shown to result in decreased serine biosynthesis (by 56%; 500 nM for 24 h) with concomitant increase in serine influx as a compensating mechanism for maintaining cellular serine level necessary for supporting A549 proliferation. Simultaneous PKM2 activation by drug treatment and culture serine withdrawal results in depletion of cellular serine pool (by ~70% in 24 h) and induction of cytostatic A549 growth arrest (by 56%; 72 h 1 µM drug treatment in BME + NEAA - Ser), but not apoptosis. Serine-dependent proliferation inhibition upon PKM2 activation is reported to be cell-specific, while it is observed in A549 and H460 cultures, SW480 and H522 are not affected.
A cell-permeable quinoline-sulfonamide that acts as a potent allosteric PKM2 activator both in cell-free enzymatic assays (AC₅₀ = 17 nM with 40 ng PKM2/200 µL) and in cultures (AC₅₀ = 45 nM 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%; 500 nM for 24 h) 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.

Cell permeable: yes
Primary Target
PKM2
Reversible: no

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Kung, C., et al. 2012. Chem. Biol.19, 1187.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

≥99% (HPLC)

100

powder

Calbiochem^®

OK to freeze
protect from light

off-white

DMSO: 5 mg/mL

2-8℃

Packaged under inert gas

11 - Combustible Solids

WGK 3