KJ Pyr 9 is a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kr?hnke 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. KJ-Pyr-9 effectively inhibits the apoptosis-linked emergence of cleaved caspase 3. KJ-Pyr-9 is capable of binding to the disordered monomeric form of MYC and that it can dissociate the intact MYC-MAX complex.
KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells.