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JND3229

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Chemical Structure| 2260886-64-2 同义名 : -
CAS号 : 2260886-64-2
货号 : A1172896
分子式 : C33H41ClN8O2
纯度 : 99%+
分子量 : 617.184
MDL号 : MFCD32644591
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(19.44 mM)，配合低频超声助溶，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 WT, IC50:6.8 nM

  • mutant EGFR

    EGFR L858R/T790M, IC50:30.5 nM
描述 The epidermal growth factor receptor (EGFR) is one of the most validated molecular targets for anticancer drug discovery. Three generations of EGFR inhibitors have been approved by US FDA and achieved significantly clinical benefit in nonsmall cell lung cancer (NSCLC) patients [1]. JND3229 is a highly potent and fourth-generation EGFRC797S reversible inhibitor with IC50 value of 5.8 nM, and also potently suppressed EGFR L858R/T790M and EGFRWT with IC50 values of 30.5 and 6.8 nM [1]. JND3229 potently inhibited the phosphorylation of EGFR L858R/T790M/C797S and EGFR19D/T790M/C797S in a dose-dependent manner. JND3229 potently inhibited the proliferation of BaF3 cells harboring the EGFR L858R/T790M/C797S and EGFR19D/T790M/C797S mutations with IC50 values of 0.51 and 0.32 μM, respectively. JND3229 also obviously suppressed the proliferation of A431 cancer cells overexpressing EGFRWT with an IC50 value of 0.27 μM [1]. The in vivo anticancer efficacy of JND3229 was also examined using a xenograft mouse model. Administration of JND3229 caused an obvious suppression of tumor growth with a tumor growth inhibition (TGI) value of 42.2%. Further immunohistochemistry analysis demonstrated that JND3229 treatment significantly decreased the level of phosphorylated EGFR (p-EGFR) in the tumor tissues [1].
作用机制 JND3229 was accommodated in the ATP binding site of the C797S-mutated EGFR with a reversible “U-shaped” configuration [1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.62mL

0.32mL

0.16mL

8.10mL

1.62mL

0.81mL

16.20mL

3.24mL

1.62mL
参考文献

[1] Lu X. Discovery of JND3229 as a New EGFRC797S Mutant Inhibitor with In Vivo Monodrug Efficacy. ACS Med Chem Lett. 2018 Oct 8;9(11):1123-1127. doi: 10.1021/acsmedchemlett.8b00373.