Biological Activity
pi-103 is a dual inhibitor of pi3k/akt and mtor with ic50 value of 0.002 μm , 0.003μm, 0.003μm, 0.015μm, 0.030μm for p110α, p110β, p110γ, p110 and mtor, respectively [1].pi3k/akt/mtor pathway is an intracellular signaling pathway and plays an important role in regulating cell cycle. it has been shown that pi3k/akt/mtor pathway is directly related to cellular quiescence, proliferation, cancer, and longevity. and many studies have shown that activation of the pi3k/akt signaling pathway is correlated with poor prognosis in a variety of cancers which demonstrated that inhibition of the pathway may be regarded as a promising therapy [2, 3].pi-103 is a selective pi3k/akt and mtorc1 inhibitor. when tested with leukemic cell lines (molm14, oci-aml3 and mv4-11) with activation of pi3k/akt, mtorc1 and erk/mapk signaling pathways, pi-103 blocked cells proliferation via inhibiting pi3k/akt and mtorc1 activity in a concentration of 1μm [4]. in hcc cell line--huh7 cells, treated pi-103 alone or combined with sorafenib inhibited cells proliferation in a dose-dependent manner through inhibition of pi3k/akt and mtorc1 pathways [5]. when tested with u87mg glioblastoma cells, pi-103 treatment in 30 nm/l showed significant inhibition of pi3k/akt and mtorc1 phosphorylation [1]. in neuroblastoma cell lines sk-n-be (2), imr-32 with amplified mycn, pi-103 inhibited cell growth in a time- and concentration-dependent manner via inhibiting pi3k/akt and mtorc1 activity [3].in sk-n-be (2) with mycn-mutant xenografted nude mice model, treated pi-103 intraperitoneally (10 mg/kg) markedly reduced the tumor volume index and tumor weight via inhibiting pi3k/ mtor pathways [1].
References
[1]. raynaud, f.i., et al., biological properties of potent inhibitors of class i phosphatidylinositide 3-kinases: from pi-103 through pi-540, pi-620 to the oral agent gdc-0941. mol cancer ther, 2009. 8(7): p. 1725-38.
[2]. hambright, h.g., et al., inhibition of pi3k/akt/mtor axis disrupts oxidative stress-mediated survival of melanoma cells. oncotarget, 2015.
[3]. segerstrom, l., et al., effects of small molecule inhibitors of pi3k/akt/mtor signaling on neuroblastoma growth in vitro and in vivo. int j cancer, 2011. 129(12): p. 2958-65.
[4]. park, s., et al., pi-103, a dual inhibitor of class ia phosphatidylinositide 3-kinase and mtor, has antileukemic activity in aml. leukemia, 2008. 22(9): p. 1698-706.
[5]. gedaly, r., et al., pi-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking ras/raf/mapk and pi3k/akt/mtor pathways. anticancer res, 2010. 30(12): p. 4951-8.
