MI-463

製品コードS7816 バッチS781601

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	C₂₄H₂₃F₃N₆S
	分子量	484.54	CAS No.	1628317-18-9
Solubility (25°C)*	体外	DMSO	96 mg/mL (198.12 mM)
		Ethanol	22 mg/mL (45.4 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	MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.
in vitro	MI-463 demonstrates profound on-target activity in MLL leukemia cells. MI-463 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.23 μM, measured after 7 days of treatment in MLL leukemia cells. MI-463 is effective in inducing differentiation of MLL leukemia cells. Treatment with sub-micromolar concentrations of MI-463 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias^[1].
in vivo	MI-463 shows substantial survival benefit in mouse models of MLL leukemia. It has very favorable druglike properties, including metabolic stability and PK profile in mice. MI-463 achieves high levels in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability(∼45%). In a mouse xenograft model using MV4;11 human MLL leukemia cells implanted into BALB/c nude mice, MI-463 induces strong inhibition of tumor growth with once-daily intraperitoneal (i.p.) administration. It does not impair normal hematopoiesis in vivo^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	leukemia cells
	濃度	--
	反応時間	6 or 7 days
	実験の流れ	For viability assays, leukemia cells are plated at relevant concentrations and treated with compounds or 0.25% DMSO and cultured at 37°C for 7 days. Medium is changed at day 4, viable cell numbers are restored to the original concentration, and compounds are re-supplied. The MTT cell proliferation assay kit (Roche) is then used, and plates are read for absorbance at 570 nm using a PHERAstar BMG microplate reader. Effect of menin-MLL inhibitors on expression level is assessed by qRT-PCR after 6 days of incubation of compounds with cells, with medium changed and compound re-supply at day 3. For cell differentiation studies, leukemia cells are treated with menin-MLL inhibitors for 7 days, then harvested, washed, and incubated with Pacific Blue rat anti-mouse CD11b antibody before being analyzed by flow cytometry.
動物実験	動物モデル	C57BL/6 mice
	投薬量	15 mg/kg
	投与方法	I.V.

参考

[1] Borkin D, et al. Cancer Cell. 2015, 27(4):589-602.

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：

Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations [ J Clin Invest, 2023, 133(13)e169993]	PubMed: 37252797
The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues in Drosophila larvae [ iScience, 2023, 26(10):107726]	PubMed: 37720104
Thioguanine Induces Apoptosis in Triple-Negative Breast Cancer by Regulating PI3K-AKT Pathway [ Front Oncol, 2020, 10:524922]	PubMed: 33194583

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。