c-Myb is a gene-specific transcription factor involved in the regulation of many target genes.As with other oncoproteins, an atypical function of the c-Myb may lead to uncontrolled cell growth and division that may cause many human cancers, where the c-Myb is over-expressed.Thus, it is observations like these that have established c-Myb as an attractive target for cancer therapy.
Halting expression of the c-Myb transcription factor was done by inhibition of the DNAbinding domain in c-Myb with small organic molecules. Compounds NSC87877 and NSC675460 (structures shown below) were previously identified as potential inhibitors of theDNA-binding domain in the c-Myb.
Five analogs of NSC87877 were synthesized. The abilities of the five compounds towards inhibition of the c-Myb transcription factor were tested both in silico and in biological assays.
In silico design of novel potential inhibitors based on the structure of NSC675460 was performed, resulting in 3 new lead compounds. Synthesis of compound NSC675460 was only partially completed.