Bisindolylmaleimide V (BIM V, Ro 31-6045) is a negative control for protein kinase C (PKC)-inhibitory activity with Kd value of 100 ?M [1]. Ro 31-6045 also inhibited S6K activity with IC50 value of 8 ?M [4].
Protein kinase C plays an important role in the transduction of signals from a variety of mediators across the cell membrane. PKC regulates cell proliferation, secretion, and gene expression. Inhibition of PKC may provide therapy for diseases such as rheumatoid arthritis, cancer and AIDS [2][3].
Bisindolylmaleimide V is the inactive analogue of the protein kinase C inhibitor Ro 31-8220. Bisindolylmaleimide IV was very weak and inhibited [3H] N-methyl scopolamine binding only at the highest concentration used [1]. Ro 31-6045 also inhibited mitogen-stimulated protein kinase p70s6k/p85s6k (S6K) activity. In fibroblasts, Ro 31-6045 inhibited S6K with IC50 value of 8 ?M [4].
References:
Lazareno S, Popham A, Birdsall NJ. Muscarinic interactions of bisindolylmaleimide analogues. Eur J Pharmacol. 1998 Nov 6;360(2-3):281-4.
Toullec D, Pianetti P, Coste H, et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771-81.
Davis PD, Hill CH, Lawton G, et al. Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
Marmy-Conus N, Hannan KM, Pearson RB. Ro 31-6045, the inactive analogue of the protein kinase C inhibitor Ro 31-8220, blocks in vivo activation of p70(s6k)/p85(s6k): implications for the analysis of S6K signalling. FEBS Lett. 2002 May 22;519(1-3):135-40.
