Icotinib (BPI-2009H)

製品コードS2922 バッチS292201

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₁N₃O₄
	分子量	391.42	CAS No.	610798-31-7
Solubility (25°C)*	体外	DMSO	78 mg/mL (199.27 mM)
		Ethanol	7 mg/mL (17.88 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	Icotinib (BPI-2009H) is a potent and specific EGFR inhibitor with IC50 of 5 nM, including the EGFR, EGFR(L858R), EGFR(L861Q), EGFR(T790M) and EGFR(T790M, L858R).
in vitro	Icotinib inhibits EGFR activity in a dose-dependent manner, with an IC50 value of 5 nM and complete inhibition at 62.5 nM. Icotinib selectively solely inhibits the EGFR members including the wild type and mutants with inhibition efficacies of 61-99%. Icotinib blocks EGFR-mediated intracellular tyrosine phosphorylation in human epidermoid carcinoma A431 cells in a dose-dependent manner. Meanwhile, in our proliferation assay performed on A431, BGC-823, A549, H460, HCT8, KB and Bel-7402 cell lines, we found that the relative sensitivity of cell lines to Icotinib is A431 > BGC-823 > A549 > H460 > KB > HCT8 and Bel-7402. Icotinib exhibits a broad spectrum of antitumor activity and it is especially effective against tumors expressing higher levels of EGFR. ^[1]
in vivo	Icotinib shows an antitumor effect in different types of xenografts. Icotinib inhibits tumor growth at a rate of 51.5%, 31.0% and 67.4% in the A431, A549 and H460 xenografts at a dose of 120 mg/kg, respectively. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical kinase assays
キナーゼアッセイ	In the in vitro kinase assays, 2.4 ng/μL EGFR protein is mixed with 32 ng/μL Crk in 25 μL kinase reaction buffer containing 1 μM cold ATP and 1 μCi ³²P-γ-ATP. The mix is incubated with Icotinib at 0, 0.5, 2.5, 12.5 or 62.5 nM on ice for 10 min followed by incubation at 30 °C for 20 min. After quenching with SDS sample buffer at 100 °C for 4 min, the protein mix is resolved by electrophoresis in a 10% SDS-PAGE gel. The dried gel is then exposed to the PhosphorImager to detect radioactivity. Quantification is performed by ImageQuant software. In this methodology the radioactive signal inversely correlates with kinase activity.
細胞アッセイ	細胞株	A431, BGC-823, A549, H460, HCT8, KB and Bel-7402 cells.
	濃度	~25 μM
	反応時間	96 h
	実験の流れ	Cells (10³ /well) are seeded into 96-well plates in RPMI-1640 medium containing 10% FBS and grown in a 5% CO₂ incubator at 37 °C. After 24 h, cells are treated with Icotinib at 0, 0.78, 1.56, 3.125, 6.25, 12.5 or 25 μM for 96 h. Cell proliferation is calculated by subtracting the mean absorbance value on day 0 from the mean absorbance value on day 4.
動物実験	動物モデル	A431, A549, H460 and HCT8 xenografts Nude mice
	投薬量	30, 60 and 120 mg/kg/day
	投与方法	p.o.

参考

[1] Tan F, et al. Lung Cancer, 2012, 76(2), 177-182.

カスタマーフィードバック

: , , Oncotarget, 2015, 5(12):4529-42.

: Data from [Data independently produced by , , Oncogene, 2017, 36(45):6235-6243]

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：

Genetic alterations predict poor efficacy, outcomes and resistance to second-line osimertinib treatment in non-small cell lung cancer [ Am J Cancer Res, 2024, 14(1):33-51]	PubMed: 38323283
A community challenge for a pancancer drug mechanism of action inference from perturbational profile data [ Cell Rep Med, 2022, 3(1):100492]	PubMed: 35106508
Defining the sensitivity landscape of EGFR variants to tyrosine kinase inhibitors [ Transl Res, 2022, S1931-5244(22)00244-4]	PubMed: 36347492
Sensitivity analysis of EGFR L861Q mutation to six tyrosine kinase inhibitors [ Clin Transl Oncol, 2022, 10.1007/s12094-022-02854-3]	PubMed: 35666454
HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. [ Nat Cell Biol, 2019, 21(8):1027-1040]	PubMed: 31332347
BIN1 reverses PD-L1-mediated immune escape by inactivating the c-MYC and EGFR/MAPK signaling pathways in non-small cell lung cancer [Wang J Oncogene, 2017, 36(45):6235-6243]	PubMed: 28714960
CD166-mediated epidermal growth factor receptor phosphorylation promotes the growth of oral squamous cell carcinoma [Guodong Jia, et al. Oral Oncology, 2016, 10.1016/j.oraloncology.2016.05.010]
Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2. [Wang DS, et al. Oncotarget, 2015, 5(12):4529-42]	PubMed: 24980828

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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