only select combinations of monomers from our library were able to demonstrate an inhibition of the Myc:Max interaction, suggesting that NBI-56418 connector and linker properties are critical for the formation of an 1009820-21-6 active dimer. It should be noted that this minimizes the possibility that non-specific binding of a large dimer is responsible for the inhibitory effects we observe, as pairs with similar capacity to form a dimer do not show any inhibition of the Myc:Max interaction. Fourthly, we observe anti-proliferative effects with dimers in two Myc over-expressing cell lines but not in a BCR-Abl dependent line. The anti-proliferative effects are correlated with selective decreases in the level of Myc protein, an effect that has previously been observed with 10058-F4 and 10074-G5 like molecules . Finally, we observe an impact on Myc-dependent gene expression with the dimeric inhibitor but not the non-dimerizable control combination, confirming the expected functional consequences of directly targeting the Myc protein. Taken together these data strongly suggest that modifying and reversibly linking these two parents molecules has generated a selective dimeric inhibitor of Myc with enhanced potency over the component monomeric inhibitors. These first steps in identifying a dimeric inhibitor of Myc provide a good starting point for further optimization to develop an inhibitor that may have the correct attributes to move into clinical testing. As well as modifications in the core ligands to improve target binding properties, as is done with traditional medicinal chemistry approaches, optimization of the connector and linker groups could significantly improve dimerization constants, cell permeability, and the metabolic profile of these inhibitors. Once optimized, there are a large number of indications where these inhibitors may find clinical utility. Many hematological cancers exhibit functional deregulation of Myc through genomic amplification or translocation of the Myc gene while many solid tumors, such as colorectal and lung cancer are also reported to have aberrant function of MYC, primarily caused by genomic amplification . In addition, the Myc family member N-Myc has be