Oncrasin-1

A cell-permeable indolecarboxaldehyde compound that selectively induces apoptosis in cells harboring mutant K-Ras both in vitro (IC₅₀ = 0.11, 0.25, 1.0, 1.58, and 4.81 µM in H2887, H460, H2122, A549, and T29Kt1 cultures, respectively) and in vivo (75% suppression of H460-derived tumor growth in mice; 100 mg/kg via daily i.p.), while exhibiting little or much reduced potency toward cells with wild-type Ras or mutant N-Ras (IC₅₀ ≥31 µM). Oncrasin-1 treatment is shown to induce PKCι aggregation with splicing factors in the nucleus and dissociation between PKCι and CDK9/Cyclin T1 in K-Ras mutant cultures, resulting in decreased RNA polymerase II phosphorylation and a suppression of RNA processing in general. Oncrasin-1-induced cell death requires the presence of both mutant K-Ras and PKCι, siRNA-mediated knockdown of either enzyme is demonstrated to abolish its cytotoxicity in H460 and T29Kt1 cultures.

Packaged under inert gas

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

Guo, W., et al. 2009. Mol. Cancer Ther.8, 441.
Guo, W., et al. 2008. Cancer Res.68, 7403.

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

Toxicity: Irritant (B)