A-485

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、选择性的、细胞和体内活性的 p300/CBP 催化抑制剂，IC50 为 9.8/2.6 nM。

A potent, selective and, cell and in vivo active p300/CBP catalytic inhibitor with IC50 of 9.8/2.6 nM; displays selectivity for p300/CBP over other HATs and histone methyltransferases in cells; dose-dependently decreases H3K27Ac in prostate adenocarcinoma PC-3 cells with EC50 of 73 nM; selectively inhibits proliferation in lineage-specific tumour types; inhibits the AR transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibits tumour growth in a castration-resistant xenograft model.(In Vitro):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. Treatment with A-485 does not alter p300 or CBP protein levels.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. A-485 induces a comparable decrease in H3K27Ac in all five prostate cancer cell lines.(In Vivo):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). In addition, 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. However, 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. A-485 induces a moderate 9% body weight loss, and the animals recover rapidly upon completion of the A-485 dosing regimen.

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. Treatment with A-485 does not alter p300 or CBP protein levels.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. A-485 induces a comparable decrease in H3K27Ac in all five prostate cancer cell lines.

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). In addition, 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. However, 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.A-485 induces a moderate 9% body weight loss, and the animals recover rapidly upon completion of the A-485 dosing regimen.

A485 | A 485

Chromatin/Epigenetic

HAT

HAT

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1889279-16-6

536.484

C25H24F4N4O5

>98% (HPLC)

10 mM in DMSO

O=C(N1CC(N([C@H](C(F)(F)F)C)CC2=CC=C(F)C=C2)=O)[C@@]3(OC1=O)CCC4=CC(NC(NC)=O)=CC=C43

N-(4-fluorobenzyl)-2-((R)-5-(3-methylureido)-2',4'-dioxo-2,3-dihydrospiro[indene-1,5'-oxazolidin]-3'-yl)-N-((S)-1,1,1-trifluoropropan-2-yl)acetamide

(-20℃)

With Ice Pack

≥ 2 years