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- 详细信息
- 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：
现询
- 供应商：
北京索莱宝科技有限公司
- CAS号：
1889279-16-6
- 规格：
10mg/5mg/1mg
| 规格： | 10mg | 产品价格： | ￥4990.0 |
|---|---|---|---|
| 规格： | 5mg | 产品价格： | ￥3290.0 |
| 规格： | 1mg | 产品价格： | ￥1090.0 |
| 基本信息 | |
| CAS | No.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 |
| 溶解性 | Soluble in DMSO |
| 纯度 | ≥98% |
| 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 |
| 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]. |
| 细胞实验 | 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 |
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