From the Insoluble Dye Indirubin towards Highly Active, Soluble CDK2‐Inhibitors

In search of novel antitumor therapies. The natural product indirubin (1) is one of the class of indigo dyes, insoluble in aqueous systems, employed by mankind since the Bronze Age for textile coloring. In 1999 indirubin was reported to be a modest inhibitor of the enzyme CDK2, a key target in the ongoing search for novel antitumor therapies. With the guidance of X-ray structures, indirubin was transformed to yield novel, soluble, almost colorless, highly potent CDK2 inhibitors that strongly inhibit the growth of the MCF7 tumor cell line in vitro.