Brief Description

C646 is a selective competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM; less potent for other acetyltransferases.
IC50 value: 400 nM(Ki)
Target: p300 inhibitor
in vitro: C646 treatment reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. The melanoma line WM35 and the lung cancer line H23 were quite susceptible to C646 treatment with Lys-CoA-Tat showing modest inhibitory effects in these cells. Notably, the immortalized murine fibroblast cell line, NIH3T3, was not inhibited by C646 at 20 μM suggesting a differential effect on the malignant cells evaluated.
C646 sensitized A549, H460 and H157 cells to IR with a dose enhancement ratio at 10% surviving fraction of 1.4, 1.2 and 1.2, respectively. C646 did not radiosensitize HFL-III cells. In A549 cells, but not in HFL-III cells, C646 (i) enhanced mitotic catastrophe but not apoptosis, necrosis, or senescence after IR; (ii) increased the hyperploid cell population after IR; and (iii) suppressed the phosphorylation of CHK1 after IR. In the presence of the specific inhibitor of p300 acetyltransferase activity, C646, EDAG was unable to accelerate erythroid differentiation, indicating an involvement of p300 acetyltransferase activity in EDAG-induced erythroid differentiation. C646 inhibited cellular proliferation, reduced colony formation, evoked partial cell cycle arrest in G1 phase, and induced apoptosis in AE-positive AML cell lines and primary blasts isolated from leukemic mice and AML patients.
in vivo: C646 infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord.

Solubility

DMSO 13 mg/ml; Water < 1 mg/ml

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Red solid