zipalertinib (TAS6417)

製品コードS8814 バッチS881401

化学情報

	Synonyms	CLN-081, TPC-064	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₃H₂₀N₆O
	分子量	396.44	CAS No.	1661854-97-2
Solubility (25°C)*	体外	DMSO	79 mg/mL (199.27 mM)
		Ethanol	79 mg/mL (199.27 mM)
		Water	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	zipalertinib (TAS6417) is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. IC50 values ranges from 1.1 ± 0.1 to 8.0 ± 1.1 nmol/L.
in vitro	Of the 255 kinases tested, TAS6417 inhibits 25 kinases other than EGFR with IC50 values less than 1,000 nmol/L, which was 100 times higher than its IC50 value against WT EGFR. It inhibits only six kinases containing TXK, BMX, HER4, TEC, BTK, and JAK3, with IC50 values less than 10 times that against WT EGFR. TAS6417 inhibits proliferation of Ba/F3 cells driven by various EGFR exon 20 insertion mutations, with IC50 values ranging from 5.05 ± 1.33 nmol/L to 150 ± 53 nmol/L. It also suppresses the growth of cells expressing exon 20 insertion mutations of the EGFR gene, with a GI50 value of 86.5 ± 28.5 nmol/L for LXF 2478L cells and 45.4 ± 2.6 nmol/L for NCI-H1975 EGFR D770_N771insSVD cells. TAS6417 has no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells^[1].
in vivo	TAS6417 causes persistent tumor regression in vivo in EGFR exon 20 insertion-driven tumor models. The tumor regression occurrs quickly after TAS6417 treatment and persists during the treatment period. Pharmacokinetic analysis reveals that the plasma concentration of TAS6417, administered at 50 and 100 mg/kg to mice, decreases rapidly in the first 4 hours. In contrast, although the effective doses in the rat model exhibit lower maximum plasma concentration (Cmax) values than those in the mouse model, the plasma concentrations tend to be more persistent, lasting up to 8 hours. TAS6417 inhibits mutant EGFR in tumors but not WT EGFR in skin tissues. It prolongs survival of animals bearing lung cancer^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	LXF 2478L cells and NCI-H1975 EGFR D770_N771insSVD cells
	濃度	0-1 μM
	反応時間	6 and 24 hours
	実験の流れ	The cells are cultured with TAS6417 or afatinib and harvested 6 and 24 hours after treatment. Phosphorylation of EGFR-Tyr1068, AKT-Ser473, and ERK1/2-Thr202/Tyr204 and expression of BIM and cleaved PARP are determined using immunoblotting analysis.
動物実験	動物モデル	BALB/cAJcl-nu/nu nude mice with intrapulmonary NCI-H1975 EGFR D770_N771insSVD xenografts
	投薬量	100 mg/kg/day and 200 mg/kg/day
	投与方法	oral

参考

[1] Hasako S, et al. Mol Cancer Ther. 2018, 17(8):1648-1658.

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：

Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9]	PubMed: 37666482

Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9]

PubMed: 37666482

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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