DEL-22379
(Synonyms: N-[2,3-二氢-3-[(5-甲氧基-1H-吲哚-3-基)亚甲基]-2-氧代-1H-吲哚-5-基]-1-哌啶丙酰胺) 目录号 : GC16214
An inhibitor of ERK dimerization
Cas No.:181223-80-3
Sample solution is provided at 25 µL, 10mM.
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DEL-22379 is an inhibitor of the dimerization of ERK with IC50 values ranging from 150-400 nM regardless of genotypes in oncogenic cells [1].
As an spatial regulator of ERK signals, ERK dimerization is essential. Impeding ERK dimerization can result in the impeding of ERK signals’ extranuclear component and hence result in curtailing tumor development and cellular transformation [1].
In HEK293 cells, DEL-22379 abolished EGF-stimulated ERK dimerization. In these cells, the EGF-induced co-immunoprecipitation of hemagglutinin- or FLAG epitopes- tagged ectopic ERK2 molecules, was abolished by DEL-22379 with an IC50 value of ~0.5 µM. In both assays, the inhibition of DEL-22379 to ERK dimerization was not associated with ERK phosphorylation. In the cytoplasm of EGF-stimulated HeLa cells, ERK dimerization was prominent, but previous treatment with DEL-22379 also resulted in no detected ERK dimmers [1].
In nude mice with some of the aforementioned tumor cell lines, DEL-22379 at a dose of 15 mg/kg inhibited ERK dimerization evidently in xenografted tumors and in liver extracts. DEL-22379 inhibited the tumor progression of A375 cells (BRAF mutant) markedly. Activated-RAS-driven tumors were very sensitive to DEL-22379. Data indicated that tumorigenesis had greater requirements for ERK dimerization than for proliferation. In tumors, treatment with DEL-22379 resulted in extensive mucinous differentiation and cell death [1].
Reference:
[1]. Herrero A, Pinto A, Colón-Bolea P, et al. Small molecule inhibition of ERK dimerization prevents tumorigenesis by RAS-ERK pathway oncogenes. Cancer cell, 2015, 28(2): 170-182.
Cell experiment: | HEK293T cells are plated at a density of 1,000-2,000 cells/well and treated with DEL-22379 (0.2-1 μ M) for 48 hr, Alamar Blue is added, and the colorimetric change is measured at 570 and 600 nm. GI50 is estimated by nonlinear regression using GraphPad5 Prism Software. Apoptosis is analyzed by evaluating caspase 3 activity, either by western blotting or using the Caspase-Glo 3/7 luminogenic assay[1]. |
Animal experiment: | Mice[1]Cancer cells are xenografted in female, athymic nu/nu mice of 8 weeks of age. 3×106 cells are injected subcutaneously in the lateral flank and allowed to develop for 10-15 days before treatment with DEL-22379 at 15 mg/kg every 12 hr for 2 weeks. patient-derived xenografts (PDXs) are performed using patient-derived colorectal cancer cells harboring BRAFV600E from non-necrotic areas of primary adenocarcinomas from patients that undergo surgical resection. Cells are grafted in both flanks or in the cecum of NOD-SCID mice. DEL-22379 is administered by intra-peritoneal injection at a concentration of 15 mg/kg every 12 hr for 30 days[1]. |
References: [1]. Herrero A, et al. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell. 2015 Aug 10;28(2):170-82. | |
| Cas No. | 181223-80-3 | SDF | |
| 别名 | N-[2,3-二氢-3-[(5-甲氧基-1H-吲哚-3-基)亚甲基]-2-氧代-1H-吲哚-5-基]-1-哌啶丙酰胺 | ||
| 化学名 | N-(3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxoindolin-5-yl)-3-(piperidin-1-yl)propanamide | ||
| Canonical SMILES | O=C1NC2=CC=C(NC(CCN3CCCCC3)=O)C=C2C1=CC4=CNC5=CC=C(OC)C=C54 | ||
| 分子式 | C26H28N4O3 | 分子量 | 444.53 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: slightly soluble | 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 | 2.2496 mL | 11.2478 mL | 22.4957 mL |
| 5 mM | 0.4499 mL | 2.2496 mL | 4.4991 mL |
| 10 mM | 0.225 mL | 1.1248 mL | 2.2496 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。
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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