The histone acetyltransferase p300/CBP is a transcriptional coactivator involved in many regulatory pathways during tumorigenesis. C646 is a selective and competitive p300 inhibitor with a Ki value of 400nM. Treatment of C3H 10T1/2 mouse fibroblasts with C646 (25μM) resulted in a reduction in the levels of histone H3 and H4 acetylation. C646 at a concentration of 25μM also inhibited TSA-induced acetylation in mouse fibroblasts. C646 at 10μM was capable of reducing 3H-thymidine incorporation in several human cancer cell lines. The IC50 value of C646 for the growth of melanoma cell line WM983A was 10-20μM[3] The suppression of P300 by C646 via intraperitoneal injection (30nmol/g/day for two weeks) reduced the level of blood glucose, rescued impaired autophagic flux, and resulted in an 18.5% increase in muscle mass in db/db mice.[4]
作用机制
C646 is a competitive, highly selective inhibitor of p300 versus other acetyltransferases.[3]
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