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).

Treating prostate adenocarcinoma PC-3 cells with A-485 for three hours leads to a dose-responsive reduction in H3K27Ac, achieving a half maximal effective concentration (EC50) of 73 nM. This compound shows its highest efficacy in hematological cancers, prominently inhibiting most multiple myeloma cell lines, as well as certain acute myeloid leukemia and non-Hodgkin’s lymphoma lines. Importantly, A-485 treatment does not affect the levels of p300 or CBP proteins but consistently decreases H3K27Ac across five different 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.