5.04537

PKM2 Activator III

• Synonym(s): PKM2 Activator III, Pyruvate Kinase M2 Activator III, N-(4-(4-(2-Methoxyphenyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide
• Empirical Formula (Hill Notation): C₂₇H₂₆N₄O₄S
• CAS Number: 1260074-86-9
• Molecular Weight: 502.58
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥99% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 5 mg/mL
• storage temp.: 2-8°C

Description

General description

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.

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
PKM2

Reversible: no

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable