C646

C646 is an inhibitor for histone acetyltransferase, and inhibits p300 with a Ki of 400 nM in a cell-free assay. Preferentially selective for p300 versus other acetyltransferases. (In Vitro) :C646 is a linear competitive inhibitor of p300 versus acetyl-CoA with a Ki of 400 nM. C646 shows a noncompetitive pattern of p300 inhibition versus H4-15 peptide substrate. C646 treatment reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. C646 has a more potent effect on cell growth than Lys-CoA-Tat does. C646 enhances mitotic catastrophe after IR and suppresses phosphorylation of CHK1 after IRin A549 cells. C646 attenuates the increased acetylation of GATA1 and the increased transcriptional activity of GATA1 induced by EDAG. (In Vivo) :Suppression of P300 by c646 (intraperitoneally injected, 30 nmol/g/d for 2 weeks) dramatically reduces the level of blood glucose in db/db mice.