Generation of potent and selective kinase inhibitors by combinatorial biosynthesis of glycosylated indolocarbazoles

摘要

We report the generation of novel glycosylated indolocarbazoles by combinatorial biosynthesis, and the identification of two novel potent and selective compounds inhibitors of JAK2 and Ikkb kinases.rnIndolocarbazole alkaloids constitute a group of natural products isolated mainly from actinomycetes that show therapeutic promise. A number of indolocarbazole analogs have entered clinical trials for cancer treatment, Parkinson's disease or diabetic retinopathy. Rebeccamycin 1 and staurosporine 2 (Fig. 1) are the lead representative members of this family.