PI-103 Hydrochloride

Short Summary : DNA-PK/PI 3-kinase/mTOR inhibitor

Category : PI3K/Akt/mTOR Signaling|PI3K

Purity : 0.98

CAS Number : 371935-79-4

Formula : C19H17ClN4O3

Molecular Weight : 384.82

SMILE : C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O.Cl

Solubility : >19.3mg/mL in DMSO

Storage : Store at -20°C

Description : PI-103 is a dual inhibitor of PI3K/Akt and mTOR with IC50 value of 0.002 M , 0.003M, 0.003M, 0.015M, 0.030M for P110, P110, P110, 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 1M [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.

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