The indirubins have been identified as the major active
components of the traditional Chinese medicine formulation
known as Danggui Longhui Wan, which has been used for
many years to treat CML in China.Of importance from
both a natural product and a pharmacological perspective,
the indirubins were recognized as being inhibitors of several
CDKs and potent inhibitors of glycogen synthase kinase-3
(GSK-3). Included in this study were 6-bromoindirubin
(92; Scheme 17), first isolated from Nature from the mollusk
Hexaplex trunculus,
257 and its chemically modified oxime
derivative BIO (93; Scheme 17), and these two compounds
demonstrated an at least 5-fold specificity versus CDK1/
cyclin B and/or CDK/p25, as well as significantly greater
specificity against a wide range of other kinases