Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Discovery of Phosphatidylinositol 3-Kinase Inhibitory Compounds from the Screening Committee of Anticancer Drugs (SCADS) Library
Dexin KongKanami YamazakiTakao Yamori
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2010 Volume 33 Issue 9 Pages 1600-1604


Identification of new uses for existing drugs is known to be an efficient approach in drug discovery. The identification of a novel phosphatidylinositol 3-kinase (PI3K) inhibitor is important in terms of cancer chemotherapy because PI3K is implicated in many types of cancer. In an effort to discover new PI3K inhibitory compounds, we recently carried out a screening of Screening Committee of Anticancer Drugs (SCADS) library, a compound library mainly composed of antitumor drugs and kinase inhibitors. As a result, six new PI3K inhibitory compounds were identified each of which displayed over 60% inhibition of PI3Kα at 10 μM. Baicalein, the most potent of these inhibitors, exhibited 73% inhibition at 1 μM. Further characterization of Baicalein and Akt inhibitor VIII showed that both compounds displayed comparable inhibition against PI3Kβ and δ, but relatively weak activity against PI3Kγ. Growth inhibition effects of Akt inhibitor VIII and Baicalein on human cancer cell line panel JFCR39 were also investigated, and the mean logarithm of the concentration required for 50% growth inhibition of cells (Log GI50) was determined to be −5.59 and −4.70, respectively. In addition, COMPARE analysis of the two compounds together with known PI3K inhibitors was carried out by using PI3K inhibitor ZSTK474 as a seed. Our results show that Akt inhibitor VIII displays a similar fingerprint to that of ZSTK474 (r=0.633), while Baicalein does not (r=0.126). These findings suggest the inhibition profile of Baicalein in cells is different from that of a typical PI3K inhibitor.

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© 2010 The Pharmaceutical Society of Japan
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