IZCZ-3
目录号 : GC65331
IZCZ-3 是有效的 c-MYC 转录抑制剂，具有抗肿瘤活性。
Cas No.:2223019-53-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IZCZ-3 is a potent c-MYC transcription inhibitor with antitumor activity[1].
IZCZ-3 (2.1 μM-15.9 μM; 24 hours) significantly inhibits SiHa, HeLa, Huh7, and A375 cancer cell proliferation (IC50s of 3.3, 2.1，4.1, and 4.2 μM, respectively). IZCZ-3 induces only weak growth inhibition in the BJ fibroblasts (IC50=15.9 μM) and mouse mesangial cells (IC50=15.6 μM), suggesting that IZCZ-3 is more effective against cancer cells than against c-MYC-independent normal cells[1]. IZCZ-3 (0-5 μM; 12 hours) induces an apparent accumulation of cells in the G0/G1 phase in SiHa cells in a dose-dependent manner[1].
IZCZ-3 (20, 10, and 5 mg/kg; intraperitoneally; every other day for 24 days) inhibits tumor growth in BALB/c nude mice with SiHa human cervical squamous cancer xenograft[1].
[1]. Hu MH, et al. Discovery of a New Four-Leaf Clover-Like Ligand as a Potent c-MYC Transcription Inhibitor Specifically Targeting the Promoter G-Quadruplex. J Med Chem. 2018 Mar 22;61(6):2447-2459.
| Cas No. | 2223019-53-0 | SDF | Download SDF |
| 分子式 | C46H49N7O | 分子量 | 715.93 |
| 溶解度 | DMSO : 5 mg/mL (6.98 mM; ultrasonic and warming and heat to 80°C) | 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 | 1.3968 mL | 6.9839 mL | 13.9678 mL |
| 5 mM | 0.2794 mL | 1.3968 mL | 2.7936 mL |
| 10 mM | 0.1397 mL | 0.6984 mL | 1.3968 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。
Insight Derived from Molecular Dynamics Simulation into the Selectivity Mechanism Targeting c-MYC G-Quadruplex
J Phys Chem B 2020 Nov 5;124(44):9773-9784.PMID:33089692DOI:10.1021/acs.jpcb.0c05029.
Stabilizing G-quadruplex (G4) structures formed in the c-MYC oncogene promoter represents a fundamental strategy for cancer therapy. However, most G4 stabilizers lack selectivity over various G4s in the genomes. By investigating the binding characteristics of a conjugated imidazole/carbazole (IZCZ-3) molecule with the G4s of c-MYC, c-KIT, and telomere through molecular docking and molecular dynamics simulations, the present study demonstrates that though the binding affinities between IZCZ-3 and the monomeric G4s are inconsistent with the experimental data, the dimeric c-MYC and c-KIT G4s can be targeted by IZCZ-3 through forming concomitant π-π stacking interactions with the intermolecular assembly producing significant contributions to the binding affinity. In the intermolecular dimeric G4-IZCZ-3 binding complexes, IZCZ-3 prefers the c-MYC G4 that has two exposed G-tetrads per monomer over the single G-tetrad-exposed c-KIT G4 by creating more aggregation effects. Taking the aggregation effects into account, the binding affinity order of IZCZ-3 follows c-MYC G4 > c-KIT G4 > telomeric G4, agreeing well with the experimental observation. Thus, the selectivity of IZCZ-3 for c-MYC G4 probably comes from its role in stabilizing the sandwichlike intermolecular aggregates, providing a framework for the development of selective stabilizers targeting c-MYC G4.
Discovery of a New Four-Leaf Clover-Like Ligand as a Potent c-MYC Transcription Inhibitor Specifically Targeting the Promoter G-Quadruplex
J Med Chem 2018 Mar 22;61(6):2447-2459.PMID:29474069DOI:10.1021/acs.jmedchem.7b01697.
Downregulating transcription of the oncogene c-MYC is a feasible strategy for cancer therapy. Stabilization of the G-quadruplex structure present in the c-MYC promoter can suppress c-MYC transcription. Thus, far, several ligands targeting this structure have been developed. However, most have shown no selectivity for the c-MYC G-quadruplex over other G-quadruplexes, leading to uncertain side effects. In this study, through structural modification of aryl-substituted imidazole/carbazole conjugates, a brand-new, four-leaf clover-like ligand called IZCZ-3 was found to preferentially bind and stabilize the c-MYC G-quadruplex. Further intracellular studies indicated that IZCZ-3 provoked cell cycle arrest and apoptosis and thus inhibited cell growth, primarily by blocking c-MYC transcription through specific targeting of the promoter G-quadruplex structure. Notably, IZCZ-3 effectively suppressed tumor growth in a mouse xenograft model. Accordingly, this work provides an encouraging example of a selective small molecule that can target one particular G-quadruplex structure, and the selective ligand might serve as an excellent anticancer agent.