AZ304

製品コードS8755 バッチS875501

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₇H₂₅N₅O₂
	分子量	451.52	CAS No.	942507-42-8
Solubility (25°C)*	体外	DMSO	90 mg/mL (199.32 mM)
		Ethanol	5 mg/mL (11.07 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	AZ304 is a synthetic inhibitor designed to interact with the ATP-binding site of wild type and V600E mutant BRAF with IC50 values of 79 nM and 38 nM, respectively. It also inhibits CRAF, p38 and CSF1R at sub 100 nM potencies.
in vitro	AZ304 shows potent inhibitory activities to the kinase domains of wild type BRAF, V600E mutant BRAF and wild type CRAF in vitro, with IC50 values of 79 nM, 38 nM and 68 nM, respectively. AZ304 potently reduces ERK phosphorylation (p-ERK), with a mean EC50 of 65 nM in the V600E mutant BRAF containing melanoma cell line A375 and an EC50 of 60 nM in the wild type BRAF containing melanoma cell line SK-MEL-31. AZ304 markedly inhibits cell proliferation in mutant BRAF cancer cell lines, and effectively reduces cell growth in selected cell lines harbouring wild type BRAF/RAS or mutant RAS. The GI50 values ranged from 0.08-7.72 μM in mutant BRAF cell lines, 0.43-11.7 μM in wild type BRAF/RAS cell lines, and 0.9-16.66 μM in mutant RAS cell lines. AZ304 exhibits anti-proliferative effects on multiple cancer types, including melanoma, colorectal cancer, leukaemia, ovarian cancer, lung cancer, and pancreatic cancer, independently of BRAF genetic status. AZ304 retains inhibitory activity against both V600E mutant and wild type BRAF CRC cell lines in the presence of the EGFR ligand EGF^[1].
in vivo	AZ304 monotherapy and its combination with Cetuximab have anti-tumour effects on RKO and Caco-2 tumour xenografts without obvious toxicity, independently of BRAF mutation status^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	cell lines containing wild type BRAF or V600E mutant BRAF (MC-F7, A549 and A375 cells)
	濃度	6.5 nM, 65 nM, 650 nM and 6.5 μM
	反応時間	75 min
	実験の流れ	In vitro p-ERK and p-P38 evaluation in cell lines containing wild type BRAF or V600E mutant BRAF: Cells are collected following 75 min treatment at 0.1, 1, 10 and 100 fold of A375 p-ERK EC50 for each compound. (A375: BRAF V600E, A549: RAS MT; MC-F7: BRAF/RAS WT)
動物実験	動物モデル	Female 4-6 weeks old athymic BALB/c nude mice inoculated with RKO/Caco-2 cells
	投薬量	10 mg/kg
	投与方法	by oral gavage

参考

[1] Ma R, et al. Br J Cancer. 2018, 118(11):1453-1463.

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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