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Chemical Structure| 1268454-23-4 同义名 : MLN1117;INK1117;TAK-117
CAS号 : 1268454-23-4
货号 : A446445
分子式 : C19H17N5O3
纯度 : 99%+
分子量 : 363.37
MDL号 : MFCD15146372
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 5 mg/mL(13.76 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p110α

    PI3Kα, IC50:21 nM
描述 The PI3K pathway is a frequently dysregulated signaling cascade in human cancer. Activating mutations in PIK3CA (encoding the p110α catalytic subunit of PI3Kα) are strongly implicated in oncogenic PI3K signaling. MLN1117 is a potent and selective oral PI3Kα isoform inhibitor (IC50 of 21 nmol/L against PI3Kα) that has demonstrated > 100-fold selectivity relative to other class I PI3K family members (PI3Kβ/γ/δ) and mTOR, and a high degree of selectivity against many other kinases. MLN1117 administration in PIK3CA-mutant tumor cell lines resulted in potent PI3K pathway inhibition, blockade of cellular proliferation, and apoptosis. MLN1117 (100 – 1200 mg) exhibited moderately fast oral absorption, a generally dose proportional increase in exposure, and plasma half-life of approximately 11 hours. Preclinical studies showed MLN1117 to have low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. Administration of MLN1117 also led to dose-dependent inhibition of tumor growth in murine xenograft models of human cancer (e.g., breast carcinoma) bearing PIK3CA oncogenic mutations, with corresponding inhibition of PI3K pharmacodynamic markers in tumor tissue[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.75mL

0.55mL

0.28mL

13.76mL

2.75mL

1.38mL

27.52mL

5.50mL

2.75mL
参考文献

[1]Yap TA, Bjerke L, et al. Drugging PI3K in cancer: refining targets and therapeutic strategies. Curr Opin Pharmacol. 2015 Aug;23:98-107.

[2]So L, Yea SS, et al. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31.

[3]A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective PI3Kα Isoform Inhibitor, in Patients with Advanced Solid Malignancies