In a fluorescence polarization screen for the MYC-MAX interaction, we have 
identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke 
pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 ± 1.0 nM, as 
determined by backscattering interferometry; KJ-Pyr-9 also interferes with 
MYC-MAX complex formation in the cell, as shown in a protein fragment 
complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic 
transformation in cell culture; it has no or only weak effects on the oncogenic 
activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes 
with the proliferation of MYC-overexpressing human and avian cells and 
specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 
effectively blocks the growth of a xenotransplant of MYC-amplified human cancer 
cells.