10074-A4
目录号 : GC63576
10074-A4 是一种 c-Myc 结合化合物，与 c-Myc370–409 结合，表现得像“蛋白质云”周围的“配体云”，具有与非结合配体截然不同的特征。具有抗癌作用
Cas No.:312631-87-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
10074-A4 is a c-Myc inhibitor. 10074-A4 could bind to c-Myc370-409 at different sites along the peptide chain. 10074-A4 has anticancer effects[1][2].
10074-A4 shows inhibitory activity of HL-60 cells with an IC50 of 15.1 μM[1].10074-A4 (25-50 μM; 24 hours) arrests the cell cycle at the S-phase in a dose-dependent manner in HL-60 cells. 10074-A4 inhibits the mRNA level of the c-Myc target genes, CCND2 and CDK4[1].10074-A4 could bind to c-Myc370-409 at different sites along the peptide chain and its binding behavior could be described as a ’ligand cloud’. Even in the bound state, the structure of the c-Myc370-409 peptide remained a dynamic ensemble. The 10074-A4 ligand bound at different sites throughout the c-Myc370-409 chain with different strength[2].
[1]. Chen Yu, et al. Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc. Sci Rep. 2016 Mar 2;6:22298.
[2]. Fan Jin, et al. Ligand clouds around protein clouds: a scenario of ligand binding with intrinsically disordered proteins. PLoS Comput Biol. 2013;9(10):e1003249.
| Cas No. | 312631-87-1 | SDF | |
| 分子式 | C18H14Cl2N2O3S | 分子量 | 409.29 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4433 mL | 12.2163 mL | 24.4326 mL |
| 5 mM | 0.4887 mL | 2.4433 mL | 4.8865 mL |
| 10 mM | 0.2443 mL | 1.2216 mL | 2.4433 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ligand clouds around protein clouds: a scenario of ligand binding with intrinsically disordered proteins
PLoS Comput Biol 2013;9(10):e1003249.PMID:24098099DOI:PMC3789766
Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets. However, drug design targeting IDPs is still in the very early stages. Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone. To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc₃₇₀₋₄₀₉ peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4. We found that the conformational space of the apo c-Myc₃₇₀₋₄₀₉ peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds. Under the binding of the ligand, c-Myc₃₇₀₋₄₀₉ remained disordered. The ligand was found to bind to c-Myc₃₇₀₋₄₀₉ at different sites along the chain and behaved like a 'ligand cloud'. In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds. Nevertheless, the binding of the ligand and a non-ligand to the c-Myc₃₇₀₋₄₀₉ target could be clearly distinguished. The present study provides insights that will help improve rational drug design that targets IDPs.