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CL-387785

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Chemical Structure| 194423-06-8 同义名 : EKI-785;WAY-EKI 785;EKB-785
CAS号 : 194423-06-8
货号 : A119062
分子式 : C18H13BrN4O
纯度 : 98%
分子量 : 381.226
MDL号 : MFCD02179194
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(31.48 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:370 pM
描述 Tumors with certain mutations in the epidermal growth factor receptor (EGFR) family genes dramatically respond to EGFR inhibitors. CL-387785 is a specific, irreversible and covalent anilinoquinazoline EGFR inhibitor. It also specifically inhibited kinase activity of the protein (IC50 = 370+/-120 pM), blocked EGF-stimulated autophosphorylation of the receptor in cells (ic50 approximately 5 nM), inhibited cell proliferation (IC50 = 31-125 nM) primarily in a cytostatic manner in cell lines that overexpress EGFR or cerbB-2, and profoundly blocked the growth of a tumor that overexpresses EGFR in nude mice (when given orally at 80 mg/kg/day for 10 days, daily)[3]. CL-387785 is able to overcome resistance caused by the T790M mutation on a functional level, correlating with effective inhibition of downstream signaling pathways[4]. CL-387,785 and blebbistatin interacted in a synergistic fashion to suppress cell proliferation and induce apoptosis in H1975 cells. The combination of CL-387,785 and blebbistatin enhanced the down-regulation of cyclooxygenase-2 (COX-2), a transcriptional target of nuclear EGFR[5]. reatment with CL-387,785, low-dose WZ4002, and high-dose WZ4002 caused mean decreases in (18)F-FLT uptake of 21%, 26%, and 36%, respectively[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.62mL

0.52mL

0.26mL

13.12mL

2.62mL

1.31mL

26.23mL

5.25mL

2.62mL
参考文献

[1]Roberts RB, Min L, et al. Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1521-6.

[2]Discafani CM, Carroll ML, et al. Irreversible inhibition of epidermal growth factor receptor tyrosine kinase with in vivo activity by N-[4-[(3-bromophenyl)amino] -6-quinazolinyl] -2-butynamide (CL-387,785). Biochem Pharmacol. 1999 Apr 15;57(8):917-25.

[3]Discafani CM, et al. Irreversible inhibition of epidermal growth factor receptor tyrosine kinase with in vivo activity by N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide (CL-387,785). Biochem Pharmacol. 1999 Apr 15;57(8):917-25.

[4]Kobayashi S, et al. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res. 2005 Aug 15;65(16):7096-101.

[5]Huan-Chih Chiu,et al. EGFR and myosin II inhibitors cooperate to suppress EGFR-T790M-mutant NSCLC cells. Mol Oncol. 2012 Jun;6(3):299-310.

[6]Antonella Zannetti,et al. 3'-deoxy-3'-18F-fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer.