ADTL-EI1712
目录号 : GC46808
A dual ERK1 and ERK5 inhibitor
Cas No.:2414916-45-1
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
ADTL-EI1712 is a dual inhibitor of ERK1 and ERK5 (IC50s = 40.43 and 64.5 nM, respectively).1 It reduces ERK1 and ERK5 activity by 93.5% and 89.4%, respectively, but also inhibits ERK2 activity by 92.7%, in a panel of 100 kinases at 1 µM. ADTL-EI1712 inhibits proliferation of HL-60 and MKN74, but not HeLa, cancer cells (IC50s = 1.26, 2.55, and >50 µM, respectively). It reduces tumor growth and intratumor phosphorylation of ERK1/2 and ERK5 in an MKN74 mouse xenograft model when administered at a dose of 50 mg/kg per day.
1.Wang, G., Zhao, Y., Liu, Y., et al.Discovery of a novel dual-target inhibitor of ERK1 and ERK5 that induces regulated cell death to overcome compensatory mechanism in specific tumor typesJ. Med. Chem.63(8)3976-3995(2020)
| Cas No. | 2414916-45-1 | SDF | |
| Canonical SMILES | O=C(C1=C(NC(C2=CC=CC=C2Cl)=O)SC3=C1CCN(C(NC4=CC=CC=C4Cl)=S)C3)N | ||
| 分子式 | C22H18Cl2N4O2S2 | 分子量 | 505.4 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml | 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 | 1.9786 mL | 9.8932 mL | 19.7863 mL |
| 5 mM | 0.3957 mL | 1.9786 mL | 3.9573 mL |
| 10 mM | 0.1979 mL | 0.9893 mL | 1.9786 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。
Discovery of a Novel Dual-Target Inhibitor of ERK1 and ERK5 That Induces Regulated Cell Death to Overcome Compensatory Mechanism in Specific Tumor Types
J Med Chem 2020 Apr 23;63(8):3976-3995.PMID:32078308DOI:10.1021/acs.jmedchem.9b01896
ERK1 and ERK5 are proposed to have pivotal roles in several types of cancer. Under some circumstance, ERK5 may provide a common bypass route, which rescues proliferation upon abrogation of ERK1 signaling. Thus, we accurately classified the tumor types from The Cancer Genome Atlas (TCGA) based on the expression levels of ERK1 and ERK5. We proposed a novel therapeutic strategy to overcome the above-mentioned compensatory mechanism in specific tumor types by co-targeting both ERK1 and ERK5. On the basis of the idea of overcoming ERK5 compensation mechanism, 22ac (ADTL-EI1712) as the first selective dual-target inhibitor of ERK1 and ERK5 was discovered to have potent antitumor effects in vitro and in vivo. Interestingly, this compound was found to induce regulated cell death accompanied by autophagy in MKN-74 cells. Taken together, our results warrant the potential of this dual-target inhibitor as a new candidate drug that conquers compensatory mechanism in certain tumor types.