<?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
</style></custom4></record><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%">Kommagalla, Yadagiri</style></author><author><style face="normal" font="default" size="100%">Cornea, Sinziana</style></author><author><style face="normal" font="default" size="100%">Riehle, Robert</style></author><author><style face="normal" font="default" size="100%">Torchilin, Vladimir</style></author><author><style face="normal" font="default" size="100%">Degterev, Alexei</style></author><author><style face="normal" font="default" size="100%">Ramana, Chepuri V.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Optimization of the anti-cancer activity of the phosphatidylinositol-3 kinase pathway inhibitor PITENIN-1: switching thiourea with 1,2,3-triazole</style></title><secondary-title><style face="normal" font="default" size="100%">Medchemcomm</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">SEP</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">9</style></number><publisher><style face="normal" font="default" size="100%">ROYAL SOC CHEMISTRY</style></publisher><pub-location><style face="normal" font="default" size="100%">THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND</style></pub-location><volume><style face="normal" font="default" size="100%">5</style></volume><pages><style face="normal" font="default" size="100%">1359-1363</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We previously reported encouraging in vitro and in vivo anti-cancer activity of N-((3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl) benzamide (termed PITENIN-1). In the current work, we describe the structure-activity relationship study of the PIT-1 series, based on the replacement of a central thiourea unit with 1,2,3-triazole, which leads to increased liver microsomal stability, drug likeness and toxicity towards cancer cells.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">2.495</style></custom4></record></records></xml>