Bisindolylmaleimide I and V inhibit necrosis induced by oxidative stress in a variety of cells including neurons.

Although free radical-mediated necrosis is implicated in many diseases such as neurodegeneration, potent anti-necrotic drugs have not yet been exploited. We found that bisindolylmaleimide I (BMI or GF 109203X), a PKC inhibitor, protected a variety of cells, including neurons, from oxidant-induced necrosis, although calphostin C, another type of PKC inhibitor, and staurosporine, a broad kinase inhibitor, had no such effect. BMI was significantly protective in neuronal cells whereas chronic application of BMI induced neurotoxicity.