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- 文献和实验
- 技术资料
- 保存条件：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 保质期：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 英文名：
A-485
- 库存：
999
- 供应商：
北京索莱宝科技有限公司
- CAS号：
1889279-16-6
- 规格：
1mg/5mg/10mg
| 规格： | 1mg | 产品价格： | ¥1090.00 |
|---|---|---|---|
| 规格： | 5mg | 产品价格： | ¥3290.00 |
| 规格： | 10mg | 产品价格： | ¥4990.00 |
| CAS | 1889279-16-6 |
| 英文名称 | A-485 |
| 别名 | (1R)-N-[(4-Fluorophenyl)methyl]-2,3-dihydro-5-[[(methylamino)carbonyl]amino]-2',4'-dioxo-N-[(1S)-2,2,2-trifluoro-1-methylethyl]spiro[1H-indene-1,5'-oxazolidine]-3'-acetamide; |
| 分子式 | C25H24F4N4O5 |
| 分子量 | 536.48 |
| 规格 | 1mg ; 5mg ; 10mg |
| 溶解性 | Soluble in DMSO≥10mg/mL |
| 纯度 | ≥98% |
| 级别 | Cell Culture |
| 外观(性状) | White to off-white Solid |
| 储存条件 | Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 | 冷藏运输 |
| MDL | MFCD31619258 |
| SMILES | O=C(N1CC(N([C@@H](C)C(F)(F)F)CC2=CC=C(F)C=C2)=O)[C@]3(OC1=O)C4=CC=C(NC(NC)=O)C=C4CC3 |
| 靶点 | p300/CBP |
| 通路 | Epigenetics |
| 背景说明 | A-485是一种有效的、选择性的p300/CBP催化抑制剂。 |
| 生物活性 | A-485 is a potent and selective catalytic inhibitor of p300/CBP with IC50s of 9.8nM and 2.6nM for p300 and CBP histone acetyltransferase (HAT), respectively[1]. |
| IC50 | 9.8nM(p300)，2.6nM(CBP)[1] |
| 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[1]. |
| 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[1]. |
| 细胞实验 | The LuCap-77 CR prostate PDX model is used in this study. Donor tumors are dissociated and injected as a brie(1:2)into the right flank of 16 week old male C.B.-17 SCID mice on day 0 in a volume of 0.2 mL. Tumors are size matched on day 26 post-inoculation with a mean tumor volume of 211±3(SEM)mm3 with dosing beginning on day 28. Mice are randomized into treatment groups using Studylog software based on tumor volume. LuCap-77 CR xenograft tumors are established in SCID mice and animals are dosed with A-485 as for 7 days. Three hours post the final dose，tumors are harvested and snap frozen on dry ice[1]. |
| 动物实验 | Cell lines are plated in 96 well or 384 well plates and allowed to adhere for 24 h. The cells are then treated with A-485 for 3，4，or 5 days. Experiments are run in triplicate and the fraction of viable cells is determined using the Cell Viability Assay according to the manufacturer’s recommendations. For Thymidine incorporation assays，cells are treated with A-485 for 1，2，3，or 4 days. Twenty four hours prior to the time point，tritiated thymidine is added and cells are incubated for an additional 24 h. Genomic DNA is then isolated on filter plates[1]. |
| 数据来源文献 | [1]. Lasko LM， et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct 5;550(7674):128-132. |
| 单位 | 瓶 |
| 表格1 | |*|1mg|5mg|10mg|$$|1mM|1.864mL|9.32mL|18.64mL|$$|5mM|0.3728mL|1.864mL|3.728mL|$$|10mM|0.1864mL|0.932mL|1.864mL| |
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文献和实验3.552 3.850 21 0.686 1.323 1.721 2.080 2.518 2.831 3.135 3.527 3.819 22 0.686 1.321 1.717 2.074 2.508 2.819 3.119 3.505 3.792 23 0.685 1.319 1.714 2.069 2.500 2.807 3.104 3.485 3.768 24 0.685 1.318 1.711 2.064 2.492 2.797 3.091
标准曲线的制作吸取0.25ml 0.4%TTC溶液放入10ml容量瓶，加少许Na2S2O4粉末，摇匀后立即产生红色的TTF。再用乙酸乙酯定容至刻度，摇匀。然后分别取此液0.25ml、0.5ml、1.00ml、1.50ml、2.00ml置10ml容量瓶中，用乙酸乙酯定容至刻度，即得到含TTF25μg、50μg、100μg、150μg、200μg的标准比色系列，以空白作参比，在485nm波长下测定光密度，绘制标准曲线。（2）称取根样品0.5g，放入小培养皿（空白试验先加硫酸再加入根样品，其他操作相同
（达8通道）。 （6）有485通讯功能。 缺点包括： （1）软管容易破裂。 （2）仪器及软管容易堵塞，需要定期清洗。 （3）仪器工作时噪声比较大。 6、【仪器外观描述或者图片】： 7、【说明书或者操作规范】： （1）安装泵头和软管 （2）启/停操作：在正常状态按一下启/停键，泵开始运行，再按一下泵就停止。 （3）方向控制：在正常状态按动方向键可以改变泵的工作方向。 （4）调速：顺时针转动旋钮则流量增加，反之减少。 （5）设置显示模式：可以进行流量和转速的显示，厂家默认
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