Theliatinib (HMPL-309)

製品コードS8584

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₅H₂₆N₆O₂
	分子量	442.51	CAS No.	1353644-70-8
Solubility (25°C)*	体外	DMSO	47 mg/mL (106.21 mM)
		Ethanol	'-1 mg/mL

* <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	Theliatinib (HMPL-309) is a highly potent EGFR inhibitor with Ki value of 0.05 nM against the wild type EGFR and IC50 values of 3 nM and 22 nM against EGFR and EGFR T790M/L858R mutant. It demonstrats 50 fold greater selectivity for EGFR compared to 72 other kinases.
in vitro	In comparison to erlotinib or gefitnib, theliatinib (HMPL-309) shows much stronger binding affinity to wild type EGFR and is more difficult to be replaced by ATP. This unique feature may result in better target engagement for this compound compared to erlotinib or gefitinib, leading to stronger anti-tumor activity in tumors with wild type EGFR activation due to gene amplification or protein overexpression. It inhibits EGFR phosphorylation with an IC50 of 0.007 μM for EGF stimulated EGFR phosphorylation in A431 cells and cell survival in tumor cells with wild-type EGFR (A431, H292, FaDu cells)^[1].
in vivo	Theliatinib (HMPL-309) demonstrates dose-dependent anti-tumor activity in a panel of PDECX (patient-derived esophageal cancer xenograft) models with a generally good correlation between EGFR H score and tumor growth inhibition. Furthermore, aberrant activation or gene mutations of other targets such as PI3K and FGFR diminish the anti-tumor activity of EGFR TKIs, especially this compound^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	A431 cells
	濃度	0.005-10 μM
	反応時間	48 h
	実験の流れ	A431 cells (1 × 10⁴ cells/well) in exponential phase are seeded in duplicates in DMEM containing 10% FBS and incubated at 37°C and 5% CO2 overnight. Then, 10 μL of test compounds (including theliatinib (HMPL-309), gefitinib and erlotinib) at tested concentrations (10~0.005 μM, 3 fold gradient dilution) are added into each well with the final concentration of DMSO at 0.5%. The cells are incubated for 48 h followed by further incubation for 1h after adding 10 μL/well CCK-8 solution. Cell survival is determined by measuring the optical density at 450 nm.
動物実験	動物モデル	Seven to nine week old NOD-SCID immunodeficient or BALB/cASlac-nu/nu male or female mice (Tumor-bearing mice)
	投薬量	15 mg/kg/day
	投与方法	oral

参考

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584209/

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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