Cyclin-dependent kinase 3 (CDK3), like CDK8, is a transcriptional regulator of the CDK family. Strikingly, CDK3 is apparently unneeded by any normal tissues, as indicated by spontaneous inactivation of CDK3 in laboratory mice. However, CDK3 is upregulated in many tumors and its inhibition selectively kills tumor cells. Senex has identified CDK3 as a tumor-specific target and has developed the first selective small-molecule inhibitors of CDK3. These inhibitors are undergoing chemical optimization in preparation to clinical development for colon cancer therapy.