PIM Kinase Inhibitor VIII, R8-T198wt

The human p27^Kip1 C-terminus PIM-1 phosphorylation site- (Thr¹⁹⁸) containing sequence is synthesized with an N-terminal Arg octamer/R8-containing sequence to facilitate its use as a cell-permeable, substrate-competitive PIM-1 inhibitor. Reported to retard human prostate carcinoma DU145-derived tumor growth in mice (100% vs 257% tumor growth on day 14 with or without 0.5 µmol/animal dosing on days 0 & 3; intratumoral injection) in vivo and completely prevents tumor expansion for up to 17 days (0.5 µmol/animal on days 0 & 5; intratumoral injection) when combined with a single Taxol (Cat. No. 580555) dosage (60 mg/kg; i.p.) on day zero. Studies using FITC-conjugated R8-T198wt confirms cellular delivery and PIM-1 interaction (K_D = 323 nM), demonstrating also that R8-T198wt-induced cell cycle arrest and apoptosis in PIM-1-expressing DU145 cells are direct consequences of inhibition of PIM-1-mediated p27^Kip1 Thr¹⁹⁸ and Bad Ser¹¹² phosphorylation, respectively.

Packaged under inert gas

Supplied as a trifluoroacetate salt

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 1 month at -20°C.

H-Gly-Gly-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Gly-Cys-Lys-Lys-Pro-Gly-Leu-Arg-Arg-Arg-Gln-Thr-OH

Morishita, D., et al. 2011. J. Biol. Chem.286, 2681.
Morishita, D., et al. 2008. Cancer Res.68, 5076.

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

Toxicity: Regulatory Review (Z)