Background:

PIK-90 is a broad-spectrum PI3K inhibitors that inhibits PI3Kα, PI3Kγ and PI3Kδ with IC50 values of 11, 18 and 58nM, respectively [1].

Studies showed that PIK-90 induced increased levels of secreted IgE at?1 μmol/L, while it inhibited IgE production at doses of greater than 2 μmol/L [2]. PIk-90 has been reported to block Akt phosphorylation. PIK-90 combined with the CDK2 inhibitor has been demonstrated to induce apoptosis in LN229?PTENWT?cells. In addition, PIK-90 combined with siRNA against both CDK1 and CDK2 has shown to induce cell death, whereas PIK-90 combined with siRNA against CDK1 or CDK2 had no apoptotic effect [3].

In vivo, PIK-90?combined with?roscovitine revealed a significant reduction of tumor size in?nude mice implanted with GBM43 cells [3].

参考文献:
[1] Van Keymeulen A1,?Wong K,?Knight ZA,?Govaerts C,?Hahn KM,?Shokat KM,?Bourne HR. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J Cell Biol.?2006 Jul 31;174(3):437-45. Epub 2006 Jul 24.
[2] Zhang TT1,?Okkenhaug K,?Nashed BF,?Puri KD,?Knight ZA,?Shokat KM,?Vanhaesebroeck B,?Marshall AJ. Genetic or pharmaceutical blockade of p110delta phosphoinositide 3-kinase enhances IgE production. J Allergy Clin Immunol.?2008 Oct;122(4):811-819.e2.
[3] Cheng CK1,?Gustafson WC,?Charron E,?Houseman BT,?Zunder E,?Goga A,?Gray NS,?Pollok B,?Oakes SA,?James CD,?Shokat KM,?Weiss WA,?Fan QW. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A.?2012 Jul 31;109(31):12722-7.