Palomid 529

Palomid 529 (P529)是新型的高效抗肿瘤PI3K/Akt/mTOR抑制剂,在NCI-60细胞系中的GI50值小于35 μM [1].Palomid 529抑制VEGF和bFGF驱动的内皮细胞增殖,IC50值分别为20 nM和30 nM.

PI3K激活AKT,随后AKT激活CREB,抑制胞浆中p27定位FOXO,激活PtdIns-3ps和能高效转录p70或4EBP1的mTOR [2, 3].

PI3K/Akt/mTOR信号通路在多种癌症中过度活化,减少凋亡并促进增殖.与促进成体干细胞的分化相比,该信号通路对促进成体干细胞的生长和增殖是必需的,尤其是神经干细胞.此外,此通路也是神经长程增强中的重要组分[4].在NSCs中,降低PI3K通路的效应,同时提高GSK3β和HB9的效应是使这些细胞更有利于神经元存活的潜在方式.放大的PI3K/AKT通路能提高神经细胞生长,以此能确定bisperoxovanadium刺激轴突生长而不致癌的适宜处理浓度.Palomid 529不仅能够抑制放射诱导的Id-1和VEGF过表达,也能下调放射诱导的MMP-2和MMP-9 [5].

参考文献：
1 Xue Q, et al.  “Palomid 529, a novel small-molecule drug, is a TORC1/TORC2 inhibitor that reduces tumor growth, tumor angiogenesis, and vascular permeability.” Cancer Res, 2008, 68(22), 9551-9557.
2 Rafalski, V.  A.; Brunet, A. "Energy metabolism in adult neural stem cell fate". Progress in Neurobiology . 2011, 93 (2): 182–203.
3 Ojeda, L.  et al. "Critical role of PI3K/Akt/GSK3β in motoneuron specification from human neural stem cells in response to FGF2 and EGF". PLoS ONE 2011, 6 (8): e23414.
4 Sui, L; Wang, J; Li, B.  M. "Role of the phosphoinositide 3-kinase-Akt-mammalian target of the rapamycin signaling pathway in long-term potentiation and trace fear conditioning memory in rat medial prefrontal cortex". Learning & Memory 2008,15 (10): 762–76.
5 Diaz R, et al.  “The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer” .Br J Cancer 2009, 100(6), 932-940.