Nazartinib (EGF816) 是一种 EGFR 抑

Nazartinib  (Synonyms: 那扎替尼; EGF816)

Nazartinib (EGF816) 是一种 EGFR 抑制剂，对 EGFR(L858R/790M) 突变体的 K_i 和 K_inact 值分别为 31 nM 和 0.222 min⁻¹。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
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生物活性    
Nazartinib (EGF816) is a covalent mutant-selective EGFR inhibitor, with Ki and Kinact of 31 nM and 0.222 min−1 on EGFR(L858R/790M) mutant, respectively.

IC50 & Target[1]    
EGFRL858R/T790M

31 nM (Ki)

体外研究
(In Vitro)    
Nazartinib (EGF816) has inhibitory effect on the mutant cell lines with IC50s of 4, 6, 2 nM in H1975, H3255, and HCC827, respectively, and demonstrates improved ADME and PK properties[1]. Nazartinib (EGF816) shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 cell lines with EC50 values of 5, 1, and 3 nM, respectively. Nazartinib inhibits cell proliferation, with EC50 values of 9, 11, and 25 nM in H3255, HCC827, and H1975, respectively. Nazartinib has an OC50 (compound concentration at 50% occupancy) value of 2 and 5 nM on HCC827 and H1975, respectively[2].

体内研究
(In Vivo)    
In H1975 mouse xenograft model, Nazartinib (EGF816; 50 and 20 mg/kg or 25 mg/kg, p.o.) demonstrates dose-dependent efficacy with near complete tumor cells regression at the highest dose tested (50 mg/kg)[1]. In H1975 mouse model, Nazartinib (EGF816; 10 mg/kg, p.o.) induces tumor growth inhibition with a T/C (tumor/control volume) of 29%, and when doses are 30 and 100 mg/kg, tumor regressions are achieved (T/C, -61% and -80%, respectively). In the H3255 xenograft model, Nazartinib (30 mg/kg, p.o.) shows significant antitumor activity. Antiproliferative activity of Nazartinib on 89 lung cancer cell lines indicates that Nazartinib selectively inhibits cell lines containing EGFR with catalytic domain mutations[2].

分子量    
495.02

性状    
Solid

Formula    
C26H31ClN6O2

CAS 号    
1508250-71-2

中文名称    
那扎替尼

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : ≥ 242 mg/mL (488.87 mM)

* "≥" means soluble, but saturation unknown.

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.0201 mL    10.1006 mL    20.2012 mL
5 mM    0.4040 mL    2.0201 mL    4.0402 mL
10 mM    0.2020 mL    1.0101 mL    2.0201 mL
*
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, 6 months; -20°C, 1 month。-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。
 

参考文献

[1]. Lelais G, et al. Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T79  [Content Brief] [2]. Jia Y, et al. 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  [Content Brief]