MKLP-2 Inhibitor, Paprotrain

A cell-permeable acrylonitrile compound that inhibits the kinesin-6 family member MKLP-2 (Mitotic kinesin-like protein 2; IC₅₀ against basal and microtubule-/MT-stimulated ATPase activity = 1.35 and 0.83 µM, respectively) in a reversible, ATP-uncompetitive (K_i = 3.36 µM), and MT-noncompetitive (K_i = 1.6 µM) manner, with little effect against the ATPase activity of 12 other kinesins (≤20% inhibition at 50 µM), including the close related MKLP-1 and MPP1 (M-phase phosphoprotein 1). Shown to inhibit cellular Aurora B and Survivin anaphase centromere-to-spindle midzone relocation in HeLa cultures (50 µM for 8 h), but not MKLP-1- or Kif4-mediated PRC1 relocation, resulting in misaligned chromosomes (70% of total metaphase cells), multipolar spindles (14% of total metaphase cells), and eventual apoptosis.

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Tcherniuk, S., et al. 2010. Angew. Chem. Int. Ed.49, 8228.

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

Toxicity: Regulatory Review (Z)