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The Identification of 2-(1 H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer

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Folkes, Adrian J., Ahmadi, Khatereh, Alderton, Wendy K., Alix, Sonia, Baker, Stewart J., Box, Gary, Chuckowree, Irina S., Clarke, Paul A., Depledge, Paul, Eccles, Suzanne A., Friedman, Lori S., Hayes, Angela, Hancox, Timothy C., Kugendradas, Arumugam, Lensun, Letitia, Moore, Pauline, Olivero, Alan G., Pang, Jodie, Patel, Sonal, Pergl-Wilson, Giles H., Raynaud, Florence I., Robson, Anthony, Saghir, Nahid, Salphati, Laurent, Sohal, Sukhjit, Ultsch, Mark H., Valenti, Melanie, Wallweber, Heidi J.A., Wan, Nan Chi, Wiesmann, Christian, Workman, Paul, Zhyvoloup, Alexander, Zvelebil, Marketa J., Shuttleworth, Stephen J.·2008·Journal of Medicinal Chemistry

DOI 10.1021/jm800295d

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Abstract

Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.

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Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients
Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858
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Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.030 · Cited by 1,627
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915

Show all 5 references

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He, Y., Sun, M. M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 1,892
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Junttila, T. T., Akita, R. W., Parsons, K., Fields, C., Lewis Phillips, G. D., Friedman, L. S., Sampath, D., & Sliwkowski, M. X. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.020 · Cited by 829
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Dowdle, W. E., Nyfeler, B., Nagel, J., Elling, R. A., Liu, S., Triantafellow, E., Menon, S., Wang, Z., Honda, A., Pardee, G., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3053 · Cited by 759
Proteogenomic characterization of pancreatic ductal adenocarcinoma
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Chappell, W. H., Steelman, L. S., Long, J. M., Kempf, R. C., Abrams, S. L., Franklin, R. A., Bäsecke, J., Stivala, F., Donia, M., Fagone, P., et al. (2011) · Oncotarget · doi:10.18632/oncotarget.240 · Cited by 510
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Kuo, K.-T., Mao, T.-L., Jones, S., Veras, E., Ayhan, A., Wang, T.-L., Glas, R., Slamon, D., Velculescu, V. E., Kuman, R. J., et al. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.081000 · Cited by 485
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LoRusso, P. M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0018 · Cited by 470
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Dienstmann, R., Rodon, J., Serra, V., & Tabernero, J. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0639 · Cited by 462
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García-Martínez, J. M., Moran, J., Clarke, R. G., Gray, A., Cosulich, S. C., Chresta, C. M., & Alessi, D. R. (2009) · Biochemical Journal · doi:10.1042/bj20090489 · Cited by 455
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Authors: Folkes, A. J., Ahmadi, K., Alderton, W. K., Alix, S., Baker, S. J., Box, G., Chuckowree, I. S., Clarke, P. A., Depledge, P., Eccles, S. A., Friedman, L. S., Hayes, A., Hancox, T. C., Kugendradas, A., Lensun, L., Moore, P., Olivero, A. G., Pang, J., Patel, S., Pergl-Wilson, G. H., Raynaud, F. I., Robson, A., Saghir, N., Salphati, L., Sohal, S., Ultsch, M. H., Valenti, M., Wallweber, H. J. A., Wan, N. C., Wiesmann, C., Workman, P., Zhyvoloup, A., Zvelebil, M. J., & Shuttleworth, S. J.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2008-08-29
Volume: 51
Issue: 18
Pages: 5522-5532
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm800295d
OpenAlex: W2029754521
Cited by: 741
References: 5
FWCI: 17.25
Type: journal article
Language: en
Open access: green

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The Identification of 2-(1 H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer

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