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ACS Medicinal Chemistry Letters
Aller, G. S.; Carson, J. D.; Diamond, M. A.; Elkins, P. A.; Gardiner,
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ASSOCIATED CONTENT
C. M.; Garver, E.; Gilbert, S. A.; Gontarek, R. R.; Jackson, J. R.;
Kershner, K. L.; Luo, L.; Raha, K.; Sherk, C. S.; Sung, C. M.; Sutton,
D.; Tummino, P. J.; Wegrzyn, R. J.; Auger, K. R.; Dhanak, D.,
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the
Mammalian Target of Rapamycin. ACS Med. Chem. Lett. 2010, 1 (1),
39ꢀ43.
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Supporting Information
Biological assays, experimental procedures and Docking
proceꢀdures. This material is available free of charge via the Inꢀ
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(13) Nishimura, N.; Siegmund, A.; Liu, L.; Yang, K.; Bryan, M.
C.; Andrews, K. L.; Bo, Y.; Booker, S. K.; Caenepeel, S.; Freeman,
D.; Liao, H.; McCarter, J.; Mullady, E. L.; San Miguel, T.;
Subramanian, R.; Tamayo, N.; Wang, L.; Whittington, D. A.;
Zalameda, L.; Zhang, N.; Hughes, P. E.; Norman, M. H.,
Phospshoinositide 3ꢀkinase (PI3K)/mammalian target of rapamycin
(mTOR) dual inhibitors: discovery and structureꢀactivity relationships
of a series of quinoline and quinoxaline derivatives. J. Med. Chem.
2011, 54 (13), 4735ꢀ4751.
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A.; Friedman, L. S.; Hayes, A.; Hancox, T. C.; Kugendradas, A.;
Lensun, L.; Moore, P.; Olivero, A. G.; Pang, J.; Patel, S.; Perglꢀ
Wilson, G. H.; Raynaud, F. I.; Robson, A.; Saghir, N.; Salphati, L.;
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C.; Wiesmann, C.; Workman, P.; Zhyvoloup, A.; Zvelebil, M. J.;
Shuttleworth, S. J., The identification of 2ꢀ(1Hꢀindazolꢀ4ꢀyl)ꢀ6ꢀ(4ꢀ
methanesulfonylꢀpiperazinꢀ1ꢀylmethyl)ꢀ4ꢀmorpholinꢀ4ꢀylꢀthieno[3,2ꢀ
d]pyrimidine (GDCꢀ0941) as a potent, selective, orally bioavailable
inhibitor of class I PI3 kinase for the treatment of cancer. J. Med.
Chem. 2008, 51 (18), 5522ꢀ5532.
(15) Burger, M. T.; Pecchi, S.; Wagman, A.; Ni, Z. J.; Knapp, M.;
Hendrickson, T.; Atallah, G.; Pfister, K.; Zhang, Y.; Bartulis, S.;
Frazier, K.; Ng, S.; Smith, A.; Verhagen, J.; Haznedar, J.; Huh, K.;
Iwanowicz, E.; Xin, X.; Menezes, D.; Merritt, H.; Lee, I.; Wiesmann,
M.; Kaufman, S.; Crawford, K.; Chin, M.; Bussiere, D.; Shoemaker,
K.; Zaror, I.; Maira, S. M.; Voliva, C. F., Identification of NVPꢀ
BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3
Kinase Inhibitor for Treating Cancer. ACS Med. Chem. Lett. 2011, 2
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(16) Maira, S. M.; Stauffer, F.; Brueggen, J.; Furet, P.; Schnell, C.;
Fritsch, C.; Brachmann, S.; Chene, P.; De Pover, A.; Schoemaker, K.;
Fabbro, D.; Gabriel, D.; Simonen, M.; Murphy, L.; Finan, P.; Sellers,
W.; GarciaꢀEcheverria, C., Identification and characterization of
NVPꢀBEZ235, a new orally available dual phosphatidylinositol 3ꢀ
kinase/mammalian target of rapamycin inhibitor with potent in vivo
antitumor activity. Mol. Cancer Ther. 2008, 7 (7), 1851ꢀ1863.
(17) Yuan, J.; Mehta, P. P.; Yin, M. J.; Sun, S.; Zou, A.; Chen, J.;
Rafidi, K.; Feng, Z.; Nickel, J.; Engebretsen, J.; Hallin, J.; Blasina,
A.; Zhang, E.; Nguyen, L.; Sun, M.; Vogt, P. K.; McHarg, A.; Cheng,
H.; Christensen, J. G.; Kan, J. L.; Bagrodia, S., PFꢀ04691502, a potent
and selective oral inhibitor of PI3K and mTOR kinases with
antitumor activity. Mol. Cancer Ther. 2011, 10 (11), 2189ꢀ2199.
(18) Venkatesan, A. M.; Dehnhardt, C. M.; Delos Santos, E.; Chen,
Z.; Dos Santos, O.; AyralꢀKaloustian, S.; Khafizova, G.; Brooijmans,
N.; Mallon, R.; Hollander, I.; Feldberg, L.; Lucas, J.; Yu, K.;
Gibbons, J.; Abraham, R. T.; Chaudhary, I.; Mansour, T. S.,
Bis(morpholinoꢀ1,3,5ꢀtriazine) derivatives: potent adenosine 5'ꢀ
triphosphate competitive phosphatidylinositolꢀ3ꢀkinase/mammalian
target of rapamycin inhibitors: discovery of compound 26 (PKIꢀ587),
a highly efficacious dual inhibitor. J. Med. Chem. 2010, 53 (6), 2636ꢀ
2645.
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AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: ymzhou@fudan.edu.cn (Prof. Zhou YM.)
lhmeng@simm.ac.cn (Prof. Meng LH)
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Author contributions
# These two authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
We gratefully acknowledge the financial support from the
NSFC (no. 21471035, 81503109), and the Shanghai Leading Acꢀ
ademic Discipline Project (B108).
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ABBREVIATIONS
PI3K, phosphoinositide 3ꢀkinase; mTOR, mammalian target of
rapamycin; SRB, sulforhodamine B; CCKꢀ8, Cell Counting Kitꢀ8
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