产品说明书

Lazertinib

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Chemical Structure| 1903008-80-9 同义名 : YH25448;GNS-1480
CAS号 : 1903008-80-9
货号 : A589050
分子式 : C30H34N8O3
纯度 : 99%+
分子量 : 554.643
MDL号 : MFCD31728331
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 8 mg/mL(14.42 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

    WT EGFR, IC50:76 nM

    L858R/T790M EGFR, IC50:2 nM

  • mutant EGFR

    Del19/T790M, IC50:1.7 nM
描述 Lazertinib is the third-generation, highly mutant-selective, irreversible and brain permeable EGFR inhibitor with IC50 values of 2 nM and 76 nM for EGFRL858R/T790M and WT EGFR, respectively. Lazertinib exhibited more potency of anti-proliferative effect on NSCLC cell lines and primary cancer cells from patients harboring EGFR mutations, shown as GI50 values were 6 nM, 5 nM, and 711 nM for H1975 cells (L858R/T790M), PC9 cells (del19) and H2073 cells (wt), respectively, and significantly increased tumor cell apoptosis compared to osimertinib. Once-daily treatment subcutaneously or intracranially with lazertinib at dose ranging in 1-25 mg/kg showed a dramatic dose-dependent tumor regression in mouse model implanted with H1975 cells, without abnormal signs such as skin keratosis shown in osimertinib-treated mice. Specially, lazertinib showed excellent penetration of the blood-brain barrier, achieving CSF concentrations exceeding the IC50 value for pEGFR inhibition in the tumor-bearing mice[1][2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.80mL

0.36mL

0.18mL

9.01mL

1.80mL

0.90mL

18.03mL

3.61mL

1.80mL
参考文献

[1]Jiyeon Y, Min HH, et al. YH25448, an irreversible 3rd generation EGFR TKI, exhibits superior anticancer effects with potent brain BBB penetration in NSCLC. Abstract 4790, Cancer Research, Volume 78, Issue 13 Supplement, pp. 4790.

[2]Min H H, In Y L, et al. P3.02b-119 YH25448, a Highly Selective 3rd Generation EGFR TKI, Exhibits Superior Survival over Osimertinib in Animal Model with Brain Metastases from NSCLC. JTO, Volume 12, Issue 1, Supplement, Pages S1265–S1266.

[3]Yun J, Hong MH, et al. YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2575-2587.