C646

C646 is a selective and competitive histone acetyltransferase p300 inhibitor with K_i of 400 nM, and is less potent for other acetyltransferases^[1]. IC50 & Target: Ki: 400 nM (histone acetyltransferase p300) In Vitro: C646 is a linear competitive inhibitor of p300 versus acetyl-CoA with a K_i 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^[1]. C646 enhances mitotic catastrophe after IR and suppresses phosphorylation of CHK1 after IRin A549 cells^[2]. C646 attenuates the increased acetylation of GATA1 and the increased transcriptional activity of GATA1 induced by EDAG^[3]. 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^[4].