A-485 是p300/CBP的一种选择性催化抑制剂，对p300和CBP组蛋白乙酰转移酶的IC50值分别为 9.8 和 2.6 nM。

A-485 is a potent and selective catalytic p300/CBP inhibitor(IC50s of 9.8 nM and 2.6 nM for p300 and CBP, respectively).

A three-hour treatment of prostate adenocarcinoma PC-3 cells with A-485 results in a dose-dependent decrease in H3K27Ac, with a half maximal effective concentration (EC50) of 73 nM. The broadest sensitivity is observed in haematological tumours, where A-485 exhibits potent activity in most multiple myeloma cell lines, and in a subset of acute myeloid leukaemia lines and non-Hodgkin’s lymphoma lines. Treatment with A-485 does not alter p300 or CBP protein levels, but it induces a comparable decrease in H3K27Ac in all five prostate cancer cell lines[1].

A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP.?A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer.?A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model.?After tumours are established in SCID male mice, twice daily intraperitoneal injections of A-485 induce 54% tumour growth inhibition after 21 days of dosing (P<0.005 as compare to vehicle control).?A-485 induces a moderate 9% body weight loss, and the animals recover rapidly upon completion of the A-485 dosing regimen[1].?In tumour-bearing animals, dosing with A-485 for seven days induces a decrease in the mRNA levels of MYC and the AR-dependent gene SLC45A3 at three hours post-dosing, and (for MYC) a decrease in the protein level, indicating that A-485 inhibits p300-mediated transcriptional activity in vivo.?But, at 16?hours post-dosing on the seventh day, A-485 drug levels in the plasma and tumour are decreased as compare to 3?hours.

1889279-16-6

C25H24F4N4O5

536.48

DMSO:100 mg/mL (186.40 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years