EAI045

製品コードS8242 バッチS824202

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H14FN3O3S
分子量 383.40 CAS No. 1942114-09-1
Solubility (25°C)* 体外 DMSO 76 mg/mL (198.22 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor.
in vitro EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (half maximal effective concentration (EC50)=2nM), but not in HaCaT cells, a keratinocyte cell line with wild-type EGFR. Despite potent inhibition of mutant EGFR, EAI045 shows no anti-proliferative effect in the H1975 and H3255 cell lines with concentrations as high as 10μM[1]. EAI045 inhibits L858R/T790M mutant with an IC50 of 3 nM. However, EAI045 is not able to completely abolish EGFR autophosphorylation in H1975 NSCLC cell line harboring the L858R/T790M mutant. Dimerization-defective/independent mutants are markedly more sensitive to EAI045. Since EGFR dimerization is required for kinase enzyme activation, EAI045 may be active against one subunit of an EGFR heterodimer/asymmetric dimer[2].
in vivo Mouse pharmacokinetic studies with EAI045 reveals a maximal plasma concentration of 0.57μM, a half-life of 2.15 h, and oral bioavailability of 26% after dosing at 20mg/kg[1]. When combined with cetuximab that blocks EGFR dimerization, EAI045 markedly reduces tumor growth in a mouse model of L858R/T790M-mutant-driven lung cancer. The mice treated alone with EAI045 do not respond. EAI045 in combination with cetuximab also induces marked tumor shrinkage in the mouse model carrying L858R/T790M/C797S, a mutant known to be resistant to all third-generation EGFR TKIs. EAI045 and cetuximab exhibits mechanistic synergy[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 H1975, H3255 and HaCaT cell lines
濃度 Serial dilution (0-100 μM)
反応時間 3 days
実験の流れ H1975, H3255 and HaCaT cell lines are plated in solid white 384-well plates at 500 cells per well in 10% FBS RPMI penicillin/streptomycin media. Using a Pin Tool, 50 nl of serial diluted compounds are transferred to the cells. After 3 days, cell viability is measured.
動物実験 動物モデル EGFR(TL) (bearing L858R/T790M point mutations) and EGFR(TD) (bearing exon19del/T790M point mutations) mice
投薬量 60 mg/kg
投与方法 by oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Synthesis and preclinical evaluation of [11C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor [ EJNMMI Res, 2024, 14(1):19] PubMed: 38363422
An UPLC-MS/MS method for the determination of EAI045 in plasma and tissues and its application to pharmacokinetic and distribution studies in rats. [ Pharmazie, 2018, 73(11):630-634] PubMed: 30396380

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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