EGF816
(Synonyms: 那扎替尼; EGF816) 目录号 : GC16321
An inhibitor of mutant EGFR
Cas No.:1508250-71-2
Sample solution is provided at 25 µL, 10mM.
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Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations respond to EGFR tyrosine kinase inhibitors (TKI) but ultimately develop resistance to these therapies. The most common resistance mechanism is a second site gate-keeper mutation within exon 20 of EGFR (T790M). EGF816 is identified as a novel covalent inhibitor of mutant-selective epidermal growth factor receptor.
In vitro: EGF816 showed sustained inhibition of pEGFR, which is consistent with the irreversible binding mechanism of EGF816. EGF816 also performs exceptionally well in long term dosing studies providing durable responses in the preclinical models [1].
In vivo: EGF816 demonstrated strong in vivo tumor regressions in several EGFR activating and resistant tumor models. In all of the models EGF816 inhibited tumor growth dose-dependently and achieved regressions of established tumors at well tolerated doses [1].
Clinical trial: A phase I/II study of EGFRmut-TKI EGF816 is being conducted to investigate the efficacy in adult patients with EGFRmut solid malignancies.
Reference:
[1] Shailaja Kasibhatla, Jie Li, Celin Tompkins, Mei-Ting Vaillancourt, Jennifer Anderson, AnneMarie Culazzo Pferdekamper, Chun Li, Oliver Long, Mathew McNeill, Robert Epple, Debbie Liao, Eric Murphy, Steve Bender, Yong Jia, Gerald Lelais. EGF816, a novel covalent inhibitor of mutant-selective epidermal growth factor receptor, overcomes T790M-mediated resistance in NSCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1733. doi:10.1158/1538-7445.AM2014-1733
| Cell experiment [1]: | |
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Cell lines |
H3255, HCC827 and H1975 cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.01 nM ~ 100 μM; 3 hrs |
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Applications |
In H3255, HCC827 and H1975 cells, EGF816 significantly lowered pEGFR levels with EC50 values of 5, 1 and 3 nM, respectively. In addition, EGF816 inhibited proliferation of H3255, HCC827 and H1975 cells with EC50 values of 9, 11 and 25 nM, respectively. |
| Animal experiment [1]: | |
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Animal models |
H1975 mouse xenograft models |
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Dosage form |
3, 10, 30 or 100 mg/kg; p.o.; q.d., for 14 days |
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Applications |
In H1975 mouse xenograft models, EGF816 (10 mg/kg) significantly inhibited tumor growth with a T/C value of 29%. At higher doses of 30 and 100 mg/kg, EGF816 inhibited tumor growth with T/C values reaching ~ 60% and ~ 80%, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Jia Y, Juarez J, Li J, Manuia M, Niederst MJ, Tompkins C, Timple N, Vaillancourt MT, Pferdekamper AC, Lockerman EL, Li C, Anderson J, Costa C, Liao D, Murphy E, DiDonato M, Bursulaya B, Lelais G, Barretina J, McNeill M, Epple R, Marsilje TH, Pathan N, Engelman JA, Michellys PY, McNamara P, Harris J, Bender S, Kasibhatla S. EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. Cancer Res. 2016 Mar 15;76(6):1591-602. | |
| Cas No. | 1508250-71-2 | SDF | |
| 别名 | 那扎替尼; EGF816 | ||
| 化学名 | (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide | ||
| Canonical SMILES | CC1=CC(C(NC2=NC3=CC=CC(Cl)=C3N2[C@]4([H])CCCCN(C(/C([H])=C([H])/CN(C)C)=O)C4)=O)=CC=N1 | ||
| 分子式 | C26H31ClN6O2 | 分子量 | 495.02 |
| 溶解度 | DMF: 33 mg/ml,DMSO: 33 mg/ml,Ethanol: 33 mg/ml,Ethanol:PBS (pH 7.2) (1:4): 0.20 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 | 2.0201 mL | 10.1006 mL | 20.2012 mL |
| 5 mM | 0.404 mL | 2.0201 mL | 4.0402 mL |
| 10 mM | 0.202 mL | 1.0101 mL | 2.0201 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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet