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GDC-0084
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GDC-0084图片
CAS NO:1382979-44-3
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
1mg电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍

化学性质

StorageStore at -20°C
M.Wt382.42
Cas No.1382979-44-3
FormulaC18H22N8O2
Solubilityinsoluble in H2O; insoluble in EtOH; ≥2.83 mg/mL in DMSO with ultrasonic
Chemical Name5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine
Canonical SMILESNC1=NC=C(C2=NC(N3CCOCC3)=C4N=C5C(C)(C)OCCN5C4=N2)C=N1
运输条件蓝冰运输或根据您的需求运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。

资料参考

 GDC-0084 is a potent and brain penetrant inhibitor of PI3K and mTOR with Ki values of 2 nM and 70 nM for PI3Kα and mTOR, respectively [1].

 Glioblastoma (GBM) is the most common primary brain tumor in adults and aberrant PI3K signaling is associated with more than 80% of cases. The PI3K pathway represents a potential target for the treatment of this disease and the inhibitors would need to freely cross the blood-brain barrier (BBB) [1][2].

GDC-0084 is a potent and brain penetrant inhibitor of PI3K and mTOR. In vitro kinase assay, GDC-0084 exhibited Ki values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. In five different GBM cell lines, GDC-0084 had antiproliferative activities with EC50 values ranging from 0.3 to 1.1 μM. GDC-0084 has excellent human metabolic stability in microsomal and hepatocyte incubations [1]. In transfected cell lines over-expressing human or mouse P-gp or BCRP, GDC-0084 was a poor substrate of these efflux transporters. In mice brain, GDC-0084 significantly lowered pAkt and pS6 levels [2].

In rats after a 15 mg/kg dose of GDC-0084, the total brain-to-plasma ratio was 1.9-3.3. In subcutaneous U87 glioblastoma tumor xenograft mice model, GDC-0084 significantly inhibited tumor growth in a dose-dependent way. GDC-0084 also concentration-dependently inhibited pAKT [1].

 

References:

[1]. Heffron TP1, Ndubaku CO1, Salphati L1, et al. Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR. ACS Med Chem Lett. 2016 Feb 16;7(4):351-6.

[2]. Salphati L, Alicke B, Heffron TP, et al. Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. Epub 2016 Sep 16.