C646
C646 是一种histone acetyltransferase抑制剂，抑制p300，无细胞试验中Ki为400 nM，相比于其它乙酰转移酶，优先作用于p300。C646 可诱导细胞周期阻滞、细胞凋亡与自噬。
C646 Chemical Structure
CAS: 328968-36-1
产品质控
批次：
纯度：
99.77%
99.77
C646相关产品
| 相关靶点 | HAT MYST GNAT p300/CBP | 点击展开 |
|---|---|---|
| 相关产品 | Curcumin Anacardic Acid MG149 A-485 WM-1119 YF-2 CPTH2 | 点击展开 |
| 相关化合物库 | 激酶抑制剂库 FDA药物库 天然产物库 已知活性药物库-I 高选择性抑制剂库 | 点击展开 |
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| Kasumi-1 | Growth inhibition assay | 10, 25 and 50 μM | 0, 24, 48, 72 h | cellular growth and colony formation were dramatically suppressed upon C646 treatment. | 23390536 |
| SKNO-1 | Growth inhibition assay | 10, 25 and 50 μM | 0, 24, 48, 72 h | cellular growth and colony formation were dramatically suppressed upon C646 treatment. | 23390536 |
| WM983B | Function assay | 10 μM and 20 μM | 24 h | a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 | 23698071 |
| WM35 | Function assay | 10 μM and 20 μM | 24 h | a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 | 23698071 |
| 1205Lu | Function assay | 10 μM and 20 μM | 24 h | a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 | 23698071 |
| Raw246.7 | Function assay | 1, 5, 10, 15, 20, 25, or 30 μM | 16 h | results in significant inhibition of LPS and IFNγ induced NF-κB promoter activity at 15 μM or higher concentrations | 26718586 |
| KATO III | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| BGC-823 | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| MGC-803 | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| SGC-7901 | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| MKN45 | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| GES-1 | Function assay | 10 μM | 6 h | C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) | 29075795 |
| SH-SY5Y | Function assay | 20 μM | 24 h | Co-treatment with 20 µM C646 suppressed the effect of TSA treatment on Alox15 mRNA expression by 65.7% | 29235036 |
| NE-4C cells | Function assay | 0-5 μM | high glucose induced increases of H4K5ac and H4K5/8/12/16ac levels in NE-4C cells are inhibited by addition of a selective CBP/p300 inhibitor C646 in a dose-dependent way (from 0 to 5 μM) | 30114346 | |
| BL21-CodonPlus(DE3)-RIL | Function assay | 10 mins | Inhibition of FLAG-tagged p300 (1195 to 1673 residues) (unknown origin) expressed in competent Escherichia coli BL21-CodonPlus(DE3)-RIL cells using histone H4 substrate incubated for 10 mins by scintillation counting method in presence of [14C]acetyl-CoA, IC50 = 9 μM. | 26701186 | |
| BL21(RIL)-DE3 | Function assay | 10 mins | Inhibition of synthetic VMA-tagged p300 (1287 to 1652 residues) (unknown origin) expressed in Escherichia coli BL21(RIL)-DE3 cells using H4-15 peptide substrate incubated for 10 mins by radiometric filter binding assay in presence of [14C]acetyl-CoA, IC50 = 1.6 μM. | 26701186 | |
| BL21(RIL)-DE3 | Function assay | 10 mins | Inhibition of synthetic VMA-tagged p300 (1287 to 1652 residues) (unknown origin) expressed in Escherichia coli BL21(RIL)-DE3 cells using H4-15 peptide substrate incubated for 10 mins by radiometric filter binding assay in presence of [14C]acetyl-CoA, Ki = 0.4 μM. | 26701186 | |
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | C646 是一种histone acetyltransferase抑制剂，抑制p300，无细胞试验中Ki为400 nM，相比于其它乙酰转移酶，优先作用于p300。C646 可诱导细胞周期阻滞、细胞凋亡与自噬。 | ||
|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | C646是一种组蛋白乙酰转移酶抑制剂，抑制p300，Ki为400 nM，选择性作用于其他乙酰转移酶。10 μM C646在体外抑制86% p300。C646是传统的，可逆p300抑制剂。C646(25μM)作用于细胞，降低组蛋白 H3 和 H4 乙酰化水平，且废除TSA诱导的乙酰化。[1]C646(20μM)作用于对雄激素敏感的阉割性前列腺癌细胞系，通过干扰AR和NF-kB通路，而诱导细胞凋亡。[2]C646作用于小鼠细胞，抑制全部H3K4me3动态乙酰化，且局部横跨启动子和诱导基因的起始位点，从而干扰RNA聚合酶II相互作用和这些基因的激活。[3] | |||
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| 激酶实验 | 放射性检测 | |||
| 使用直接放射性测定法测定对假定的p300 HAT抑制剂的IC50值。反应在20 mM HEPES (pH 7.9)中进行，包含5 mM DTT, 80μM EDTA, 40μg/ml BSA, 100μM H4-15, 和 5 nM p300。加入在一个浓度范围内的假定抑制剂，DMSO 浓度保持不变(<5%)。反应在30°C 下温育10分钟, 然后加入1:1 12C-acetyl-CoA 和 14C-acetyl-CoA 的混合物到 20 mM，开始反应。在30°C下进行10分钟后，使用14% SDS (w/v) 淬火。所有浓度按一式两份筛选。跑胶，洗涤，干燥，暴露于PhosphorImager板上，对产生的Ac-H4-15进行量化，得到IC50值。 | ||||
| 细胞实验 | 细胞系 | C3H10T1/2 | ||
| 浓度 | ~25 μM | |||
| 孵育时间 | 1 到3小时 | |||
| 方法 | 在小鼠细胞中测定组蛋白乙酰化。C3H10T1/2小鼠成纤维细胞在含10% FCS的DMEM 培养基中 在37°C下含6% CO2的环境中生长。铺满培养物在含0.5% FCS 的DMEM 培养基中静置18-20小时，然后再处理。使用如下化合物处理细胞：TSA (10 ng/ml [33 nM]), C646 (25 μM), C37 (25 μM)。使用如下浓度的抗体: 总H3 (1:10000); H4K12ac (1:2500)。兔anti-H3K9ac(1:10000)抗体内部产生。通过酸提取从细胞中分离组蛋白，经SDS和酸-尿素聚丙烯酰胺凝胶电泳分离，并通过免疫印迹分析。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | α-c-Myc Cyclin A1/2 / Cyclin E2 / p53 / p21 H3K27Ac |
|
28630312 | |
| Immunofluorescence | BRD4 / p300 |
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28630312 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | 弱灭绝训练后，C646立即注入到ILPFC，增强恐惧消退记忆的整合。[4]C646处理脊髓，衰减机械痛和热痛觉过敏，伴随着抑制COX-2表达。[5] | |
|---|---|---|
| 动物实验 | Animal Models | 小鼠 |
| Dosages | 每种情况下2×0.75 μl 注射体积, 1.5 μg, 处理 超过2分钟 | |
| Administration | 注入 ILPFC | |
化学信息&溶解度
| 分子量 | 445.42 | 分子式 | C24H19N3O6 |
| CAS号 | 328968-36-1 | SDF | Download C646 SDF |
| Smiles | CC1=CC(=C(C=C1C)[N+](=O)[O-])C2=CC=C(O2)C=C3C(=NN(C3=O)C4=CC=C(C=C4)C(=O)O)C | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 11 mg/mL ( (24.69 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 1:
I am planning to conduct IP studies in mice, any specific vehicle that you can recommend to me?
回答：
We found it can be dissolved in 5% DMSO+30% PEG 300+ddH2O at 1 mg/ml as a clear solution. It should be ok for i.p. injection.
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