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PI3K Inhibitor
No.172(January 2017)
Autophagy is a catabolic process that digests components of the cytoplasm via lysosomes and is mediated by an organelle called the autophagosome.1,2) Autophagy is regulated by various serine/threonine protein kinases, such as mTOR, AKT, MARK etc.3) Phosphoinositide 3-kinases (PI3Ks) are also a class of such enzymes regulating autophagy. Especially, the class III PI3K promotes the formation of the autophagosome vesicle4) and a complex of the PI3K and beclin controls autophagy.5)
Wortmannin (1) is a potent PI3K inhibitor. Phosphatidylinositol 3,4,5-trisphosphate formation of fMLP-stimulated neutrophils is inhibited with a dose-responsive manner of 1 (IC50: 5 nM).6) It was shown that the treatment of rat hepatocytes with 1 inhibits autophagy with an IC50 of 30 nM.7)
It has been known that the properties of induced pluripotent stem cells (iPSCs), self-renewing and differentiation, make these cells tumorigenic.8) Zouboulis et al. reported that 1 can rapidly induce apoptosis in iPSCs.9) They discussed about apoptotic elimination of remaining undifferentiated iPSCs using 1 in their article.
mTOR: mammalian target of rapamycin
AKT: from the name of AKT8 retrovirus (J. Exp. Med. 1988, 167, 1259.)
MARK: mitogen-activated protein kinase
fMLP: N-formyl-L-methionyl-L-leucyl-L-phenylalanine
AKT: from the name of AKT8 retrovirus (J. Exp. Med. 1988, 167, 1259.)
MARK: mitogen-activated protein kinase
fMLP: N-formyl-L-methionyl-L-leucyl-L-phenylalanine
References
- 1)Historical landmarks of autophagy research
- 2)Autophagy: renovation of cells and tissues
- 3)Regulation of autophagy by kinases
- 4)Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae
- 5)Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network
- 6)Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses
- 7)The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes
- 8)Variation in the safety of induced pluripotent stem cell lines
- 9)PI3K/AKT signaling pathway is essential for survival of induced pluripotent stem cells
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