<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Miao, Benchun</style></author><author><style face="normal" font="default" size="100%">Skidan, Igor</style></author><author><style face="normal" font="default" size="100%">Yang, Jinsheng</style></author><author><style face="normal" font="default" size="100%">Lugovskoy, Alexey</style></author><author><style face="normal" font="default" size="100%">Reibarkh, Mikhail</style></author><author><style face="normal" font="default" size="100%">Long, Kai</style></author><author><style face="normal" font="default" size="100%">Brazell, Tres</style></author><author><style face="normal" font="default" size="100%">Durugkar, Kulbhushan A.</style></author><author><style face="normal" font="default" size="100%">Maki, Jenny</style></author><author><style face="normal" font="default" size="100%">Ramana, C. V.</style></author><author><style face="normal" font="default" size="100%">Schaffhausen, Brian</style></author><author><style face="normal" font="default" size="100%">Wagner, Gerhard</style></author><author><style face="normal" font="default" size="100%">Torchilin, Vladimir</style></author><author><style face="normal" font="default" size="100%">Yuan, Junying</style></author><author><style face="normal" font="default" size="100%">Degterev, Alexei</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains</style></title><secondary-title><style face="normal" font="default" size="100%">Proceedings of the National Academy of Sciences of the United States of America</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Anticancer</style></keyword><keyword><style  face="normal" font="default" size="100%">PIP3 antagonist</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">NOV</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">46</style></number><publisher><style face="normal" font="default" size="100%">NATL ACAD SCIENCES</style></publisher><pub-location><style face="normal" font="default" size="100%">2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA</style></pub-location><volume><style face="normal" font="default" size="100%">107</style></volume><pages><style face="normal" font="default" size="100%">20126-20131</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3-PH domain interactions (IC50 ranges from 13.4 to 31 mu M in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">46</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">10.43
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