MI-503CAS号: 1857417-13-0分子式: C28H27F3N8S分子量: 564.63描述纯度储存/保存方法可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
MI-503 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.
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纯度 |
98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
可溶性/溶解性 |
DMSO : 25 mg/mL (44.28 mM; Need ultrasonic)
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生物活性 | |
靶点 |
Menin-MLL interaction
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In vitro(体外研究) |
Treatment of murine bone marrow cells (BMC) transformed with the MLL-AF9 oncogene with MI-503 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.22 μM, measured after 7 days of treatment. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment. MI-503 is also very effective in inducing differentiation of MLL leukemia cells and substantially increases expression of CD11b, a myeloid differentiation marker. These effects are accompanied by reduced c-kit (CD117) expression, a marker associated with leukemia stem cells (LSCs). Treatment with sub-micromolar concentrations of MI-503 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias.
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In vivo(体内研究) |
MI-503 has very favorable drug-like properties, including metabolic stability and pharmacokinetic profile in mice. It blocks hematologic tumors in vivo and reduces MLL leukemia tumor burden. MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (~75%). Prolonged treatment (38 days) with MI-503 induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues. MI-503 could substantially improve survival of MLL leukemic mice and does not impair normal hematopoiesis in vivo.
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分子结构图