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Chemical Structure| 1225037-39-7 同义名 : PQR309;PI3K-IN-2
CAS号 : 1225037-39-7
货号 : A719240
分子式 : C17H20F3N7O2
纯度 : 99%+
分子量 : 411.382
MDL号 : MFCD28902193
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(121.54 mM)，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

  • p110γ

    PI3Kγ, Kd:25 nM

  • p110β

    PI3Kβ, Kd:11 nM

  • p110α

    PI3Kα, Kd:1.5 nM

  • p110δ

    PI3Kδ, Kd:25 nM
描述 Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that play a central role in the control of cancer cell growth, proliferation, and metastasis. PI3K is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). PQR309, a potent pan-class I PI3K inhibitor, targets mTOR kinase in a balanced fashion at higher concentrations. And it displays a mTOR/PI3Kα Ki selectivity ratio in the range of 3–8[1]. In 49 lymphoma cell lines, PQR309 showed in vitro activity in most of them tested with a median IC50 value of 233 nmol/L (95% CI, 174–324 nmol/L). The arrest in proliferation was mainly due to cell cycle arrest with a block in G1 rather than to apoptosis, limited to only 2/7 cell lines[2]. The half-life of 5–8 h and an AUC0.25–12 of around 14000 h·ng/mL contributed to an excellent oral bioavailability of PQR309 (>50%). Male Beagle dogs, exposed to PQR309 at 10 mg/kg po, showed maximal drug plasma concentrations Cmax of 583 ng/mL (approximately 1.5 μM) after 60–90 min and a half-life of >7 h, which results in drug levels of approximately 0.38 μM (150 ng/mL) after 24 h. The oral bioavailability of PQR309 in male Beagle dogs was estimated to be 23%[1].
作用机制 One morpholine of PQR309 forms a hydrogen bridge with the backbone amide of Val882, a well-known and crucial interaction[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.43mL

0.49mL

0.24mL

12.15mL

2.43mL

1.22mL

24.31mL

4.86mL

2.43mL
参考文献

[1]5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology

[2]PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy