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The Identification of 2-(1H-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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Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddon Laboratories, Sutton, Surrey, SN2 5NG, United Kingdom and Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom
†The coordinates of compound 17 in PI3K p110γ have been deposited (PDB code 3DBS).
* To whom correspondence should be addressed. Phone: +44 0 1753 285823. Fax: +44 0 1753 568367. E-mail: [email protected]
‡Piramed Pharma.
∥Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddon Laboratories.
§Genentech, Inc.
⊥Breakthrough Breast Cancer Research Centre, Institute of Cancer Research.
Cite this: J. Med. Chem. 2008, 51, 18, 5522–5532
Publication Date (Web):August 29, 2008
Copyright © 2008 American Chemical Society

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    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 p110α. 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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    51. Matthew T. Burger, Sabina Pecchi, Allan Wagman, Zhi-Jie Ni, Mark Knapp, Thomas Hendrickson, Gordana Atallah, Keith Pfister, Yanchen Zhang, Sarah Bartulis, Kelly Frazier, Simon Ng, Aaron Smith, Joelle Verhagen, Joshua Haznedar, Kay Huh, Ed Iwanowicz, Xiaohua Xin, Daniel Menezes, Hanne Merritt, Isabelle Lee, Marion Wiesmann, Susan Kaufman, Kenneth Crawford, Michael Chin, Dirksen Bussiere, Kevin Shoemaker, Isabel Zaror, Sauveur-Michel Maira, and Charles F. Voliva . Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Medicinal Chemistry Letters 2011, 2 (10) , 774-779.
    52. Stephen D. Roughley and Roderick E. Hubbard . How Well Can Fragments Explore Accessed Chemical Space? A Case Study from Heat Shock Protein 90. Journal of Medicinal Chemistry 2011, 54 (12) , 3989-4005.
    53. Okseon Kim, Yujeong Jeong, Hyunseung Lee, Sun-Sun Hong, and Sungwoo Hong . Design and Synthesis of Imidazopyridine Analogues as Inhibitors of Phosphoinositide 3-Kinase Signaling and Angiogenesis. Journal of Medicinal Chemistry 2011, 54 (7) , 2455-2466.
    54. Matthew T. Burger, Mark Knapp, Allan Wagman, Zhi-Jie Ni, Thomas Hendrickson, Gordana Atallah, Yanchen Zhang, Kelly Frazier, Joelle Verhagen, Keith Pfister, Simon Ng, Aaron Smith, Sarah Bartulis, Hanne Merrit, Marion Weismann, Xiaohua Xin, Joshua Haznedar, Charles F. Voliva, Ed Iwanowicz, and Sabina Pecchi. Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors. ACS Medicinal Chemistry Letters 2011, 2 (1) , 34-38.
    55. David Moffat, Sanjay Patel, Francesca Day, Andrew Belfield, Alastair Donald, Martin Rowlands, Judata Wibawa, Deborah Brotherton, Lindsay Stimson, Vanessa Clark, Jo Owen, Lindsay Bawden, Gary Box, Elisabeth Bone, Paul Mortenson, Anthea Hardcastle, Sandra van Meurs, Suzanne Eccles, Florence Raynaud, and Wynne Aherne . Discovery of 2-(6-{[(6-Fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a Class I Selective Orally Active Histone Deacetylase Inhibitor. Journal of Medicinal Chemistry 2010, 53 (24) , 8663-8678.
    56. Kevin D. Freeman-Cook, Christopher Autry, Gary Borzillo, Deborah Gordon, Elsa Barbacci-Tobin, Vincent Bernardo, David Briere, Tracey Clark, Matthew Corbett, John Jakubczak, Shefali Kakar, Elizabeth Knauth, Blaise Lippa, Michael J. Luzzio, Mahmoud Mansour, Gary Martinelli, Matthew Marx, Kendra Nelson, Jayvardhan Pandit, Francis Rajamohan, Shaughnessy Robinson, Chakrapani Subramanyam, Liuqing Wei, Martin Wythes and Joel Morris. Design of Selective, ATP-Competitive Inhibitors of Akt. Journal of Medicinal Chemistry 2010, 53 (12) , 4615-4622.
    57. Zecheng Chen, Aranapakam M. Venkatesan, Christoph M. Dehnhardt, Semiramis Ayral-Kaloustian, Natasja Brooijmans, Robert Mallon, Larry Feldberg, Irwin Hollander, Judy Lucas, Ker Yu, Fangming Kong and Tarek S. Mansour . Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors. Journal of Medicinal Chemistry 2010, 53 (8) , 3169-3182.
    58. Steven D. Knight, Nicholas D. Adams, Joelle L. Burgess, Amita M. Chaudhari, Michael G. Darcy, Carla A. Donatelli, Juan I. Luengo, Ken A. Newlander, Cynthia A. Parrish, Lance H. Ridgers, Martha A. Sarpong, Stanley J. Schmidt, Glenn S. Van Aller, Jeffrey D. Carson, Melody A. Diamond, Patricia A. Elkins, Christine M. Gardiner, Eric Garver, Seth A. Gilbert, Richard R. Gontarek, Jeffrey R. Jackson, Kevin L. Kershner, Lusong Luo, Kaushik Raha, Christian S. Sherk, Chiu-Mei Sung, David Sutton, Peter J. Tummino, Ronald J. Wegrzyn, Kurt R. Auger, Dashyant Dhanak. Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Medicinal Chemistry Letters 2010, 1 (1) , 39-43.
    59. Aranapakam M. Venkatesan, Christoph M. Dehnhardt, Efren Delos Santos, Zecheng Chen, Osvaldo Dos Santos, Semiramis Ayral-Kaloustian, Gulnaz Khafizova, Natasja Brooijmans, Robert Mallon, Irwin Hollander, Larry Feldberg, Judy Lucas, Ker Yu, James Gibbons, Robert T. Abraham, Inder Chaudhary and Tarek S. Mansour . Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5′-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor. Journal of Medicinal Chemistry 2010, 53 (6) , 2636-2645.
    60. Daniel P. Sutherlin, Deepak Sampath, Megan Berry, Georgette Castanedo, Zhigang Chang, Irina Chuckowree, Jenna Dotson, Adrian Folkes, Lori Friedman, Richard Goldsmith, Tim Heffron, Leslie Lee, John Lesnick, Cristina Lewis, Simon Mathieu, Jim Nonomiya, Alan Olivero, Jodie Pang, Wei Wei Prior, Laurent Salphati, Steve Sideris, Qingping Tian, Vickie Tsui, Nan Chi Wan, Shumei Wang, Christian Wiesmann, Susan Wong and Bing-Yan Zhu . Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer. Journal of Medicinal Chemistry 2010, 53 (3) , 1086-1097.
    61. Christoph M. Dehnhardt, Aranapakam M. Venkatesan, Efren Delos Santos, Zecheng Chen, Osvaldo Santos, Semiramis Ayral-Kaloustian, Natasja Brooijmans, Robert Mallon, Irwin Hollander, Larry Feldberg, Judy Lucas, Inder Chaudhary, Ker Yu, Jay Gibbons, Robert Abraham and Tarek S. Mansour . Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402. Journal of Medicinal Chemistry 2010, 53 (2) , 798-810.
    62. Jeroen C. Verheijen, David J. Richard, Kevin Curran, Joshua Kaplan, Mark Lefever, Pawel Nowak, David J. Malwitz, Natasja Brooijmans, Lourdes Toral-Barza, Wei-Guo Zhang, Judy Lucas, Irwin Hollander, Semiramis Ayral-Kaloustian, Tarek S. Mansour, Ker Yu and Arie Zask . Discovery of 4-Morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as Highly Potent and Selective ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin (mTOR): Optimization of the 6-Aryl Substituent. Journal of Medicinal Chemistry 2009, 52 (24) , 8010-8024.
    63. Pawel Nowak, Derek C. Cole, Natasja Brooijmans, Matthew G. Bursavich, Kevin J. Curran, John W. Ellingboe, James J. Gibbons, Irwin Hollander, YongBo Hu, Joshua Kaplan, David J. Malwitz, Lourdes Toral-Barza, Jeroen C. Verheijen, Arie Zask, Wei-Guo Zhang and Ker Yu . Discovery of Potent and Selective Inhibitors of the Mammalian Target of Rapamycin (mTOR) Kinase. Journal of Medicinal Chemistry 2009, 52 (22) , 7081-7089.
    64. Arie Zask, Jeroen C. Verheijen, Kevin Curran, Joshua Kaplan, David J. Richard, Pawel Nowak, David J. Malwitz, Natasja Brooijmans, Joel Bard, Kristine Svenson, Judy Lucas, Lourdes Toral-Barza, Wei-Guo Zhang, Irwin Hollander, James J. Gibbons, Robert T. Abraham, Semiramis Ayral-Kaloustian, Tarek S. Mansour and Ker Yu . ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines. Journal of Medicinal Chemistry 2009, 52 (16) , 5013-5016.
    65. Mostafa E. Salem, Mohamed Samir, Ahmed H.M. Elwahy, Ahmed M. Farag, Abdelfattah M. Selim, Aiman A. Alsaegh, Marwa Sharaky, Noha Bagato, Ibrahim Taha Radwan. Design, synthesis, docking study, cytotoxicity evaluation, and PI3K inhibitory activity of Novel di-thiazoles, and bis(di-thiazoles). Journal of Molecular Structure 2024, 1301 , 137379.
    66. Jiarui Hu, Siyu Fu, Zixuan Zhan, Jifa Zhang. Advancements in dual-target inhibitors of PI3K for tumor therapy: Clinical progress, development strategies, prospects. European Journal of Medicinal Chemistry 2024, 265 , 116109.
    67. Ahmed Zayed, Dalal A. Al-Saedi, Emmanuel Ofosu Mensah, Osman Nabayire Kanwugu, Parise Adadi, Roland Ulber. Fucoidan’s Molecular Targets: A Comprehensive Review of Its Unique and Multiple Targets Accounting for Promising Bioactivities Supported by In Silico Studies. Marine Drugs 2024, 22 (1) , 29.
    68. Kinga Fanni Tóth, Dorottya Ádám, József Arany, Yesid A. Ramirez, Tamás Bíró, Jennifer I. Drake, Alison O'Mahony, Attila Gábor Szöllősi, Szilárd Póliska, Ana Kilić, Michael Soeberdt, Christoph Abels, Attila Oláh. Fluoxetine exerts anti‐inflammatory effects on human epidermal keratinocytes and suppresses their endothelin release. Experimental Dermatology 2024, 33 (1)
    69. Yoon Sun Park, Joseph kim, Yea Seong Ryu, Jai-Hee moon, Yu Jin shin, Jeong Hee kim, Seung-Woo hong, Soo-A jung, Seul lee, Seung-Mi kim, Dae Hee lee, Do Yeon kim, Hyeseon yun, Ji-Eun you, Dong Il yoon, Chul Hee kim, Dong-In koh, Dong-Hoon jin. Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer. Cancer Biology & Therapy 2023, 24 (1)
    70. Rui Chen, Zhongyuan Wang, Lijie Sima, Hu Cheng, Bilan Luo, Jianta Wang, Bing Guo, Shunyi Mao, Zhixu Zhou, Jingang Peng, Lei Tang, Xinfu Liu, Weike Liao. Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3K α inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry 2023, 38 (1)
    71. Anirudh Prahallad, Andreas Weiss, Hans Voshol, Grainne Kerr, Kathleen Sprouffske, Tina Yuan, David Ruddy, Morgane Meistertzheim, Malika Kazic-Legueux, Tina Kottarathil, Michelle Piquet, Yichen Cao, Laetitia Martinuzzi-Duboc, Alexandra Buhles, Flavia Adler, Salvatore Mannino, Luca Tordella, Laurent Sansregret, Sauveur-Michel Maira, Diana Graus Porta, Carmine Fedele, Saskia M. Brachmann. CRISPR Screening Identifies Mechanisms of Resistance to KRASG12C and SHP2 Inhibitor Combinations in Non–Small Cell Lung Cancer. Cancer Research 2023, 83 (24) , 4130-4141.
    72. Arian Jahandideh, Mahsa Yarizadeh, Maryam Noei-Khesht Masjedi, Mina Fatehnejad, Romina Jahandideh, Roben Soheili, Yeganeh Eslami, Maryam Zokaei, Ardavan Ahmadvand, Nogol Ghalamkarpour, Rajan Kumar Pandey, Mohsen Nabi Afjadi, Zahra payandeh. Macrophage’s role in solid tumors: two edges of a sword. Cancer Cell International 2023, 23 (1)
    73. Komala Ingle, Joseph F. LaComb, Lee M. Graves, Antonio T. Baines, Agnieszka B. Bialkowska, . AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor. PLOS ONE 2023, 18 (11) , e0294065.
    74. Rabina Shrestha, Tess McCann, Harini Saravanan, Jaret Lieberth, Prashanna Koirala, Joshua Bloomekatz. The myocardium utilizes a platelet-derived growth factor receptor alpha (Pdgfra)–phosphoinositide 3-kinase (PI3K) signaling cascade to steer toward the midline during zebrafish heart tube formation. eLife 2023, 12
    75. Gustavo Garcia, Nikhil Chakravarty, Sophia Paiola, Estrella Urena, Priya Gyani, Christopher Tse, Samuel W. French, Moise Danielpour, Joshua J. Breunig, David A. Nathanson, Vaithilingaraja Arumugaswami. Differential Susceptibility of Ex Vivo Primary Glioblastoma Tumors to Oncolytic Effect of Modified Zika Virus. Cells 2023, 12 (19) , 2384.
    76. Mehrdad Hashemi, Afshin Taheriazam, Pouria Daneii, Aria Hassanpour, Amirabbas kakavand, Shamin Rezaei, Elahe Sadat Hejazi, Maryam Aboutalebi, Hamidreza Gholamrezaie, Hamidreza Saebfar, Shokooh Salimimoghadam, Sepideh Mirzaei, Maliheh Entezari, Saeed Samarghandian. Targeting PI3K/Akt signaling in prostate cancer therapy. Journal of Cell Communication and Signaling 2023, 17 (3) , 423-443.
    77. Davide Cirillo, Marta Diceglie, Marc Nazaré. Isoform-selective targeting of PI3K: time to consider new opportunities?. Trends in Pharmacological Sciences 2023, 44 (9) , 601-621.
    78. Tamara A.M. Chessa, Piotr Jung, Arqum Anwar, Sabine Suire, Karen E. Anderson, David Barneda, Anna Kielkowska, Barzan A. Sadiq, Ieng Wai Lai, Sergio Felisbino, Daniel J. Turnham, Helen B. Pearson, Wayne A. Phillips, Junko Sasaki, Takehiko Sasaki, David Oxley, Dominik Spensberger, Anne Segonds-Pichon, Michael Wilson, Simon Walker, Hanneke Okkenhaug, Sabina Cosulich, Phillip T. Hawkins, Len R. Stephens. PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate. Molecular Cell 2023, 83 (16) , 2991-3009.e13.
    79. Addie Woicik, Mingxin Zhang, Janelle Chan, Jianzhu Ma, Sheng Wang. Extrapolating heterogeneous time-series gene expression data using Sagittarius. Nature Machine Intelligence 2023, 5 (7) , 699-713.
    80. Yunxin Duan, Haodong Cheng, Lili Zhuang, Jiawei Xia, Yerong Xu, Ruyue Zhang, Rui Sun, Tao Lu, Yadong Chen. Discovery of Thieno[3,2-d]pyrimidine derivatives as potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) kinase. European Journal of Medicinal Chemistry 2023, 255 , 115370.
    81. Alexander Tyshkovskiy, Siming Ma, Anastasia V. Shindyapina, Stanislav Tikhonov, Sang-Goo Lee, Perinur Bozaykut, José P. Castro, Andrei Seluanov, Nicholas J. Schork, Vera Gorbunova, Sergey E. Dmitriev, Richard A. Miller, Vadim N. Gladyshev. Distinct longevity mechanisms across and within species and their association with aging. Cell 2023, 186 (13) , 2929-2949.e20.
    82. Weiwei Xu, M.M. Fahd Qadir, Daniela Nasteska, Paula Mota de Sa, Caroline M. Gorvin, Manuel Blandino-Rosano, Charles R. Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B. Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N. Sure, Siva S.V.P. Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E. Frigo, Xiaowen Liu, Prasad V. Katakam, Wiebke Arlt, Jochen Buck, Lonny R. Levin, Tony Hu, Jay Kolls, Charles F. Burant, Alejandra Tomas, Matthew J. Merrins, Debbie C. Thurmond, Ernesto Bernal-Mizrachi, David J. Hodson, Franck Mauvais-Jarvis. Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells. Cell Reports 2023, 42 (5) , 112529.
    83. Alexandre Bertucci, François Bertucci, Anthony Gonçalves. Phosphoinositide 3-Kinase (PI3K) Inhibitors and Breast Cancer: An Overview of Current Achievements. Cancers 2023, 15 (5) , 1416.
    84. Kerong Guo, Jian Li, Yingdong Jia, Xiaojuan Yang, Xiqing Yan, Liqiang Wu. Design, synthesis, and biological evaluation of quinolinedione-linked sulfonylpiperazine derivatives as NQO1-directed antitumor agents. Bioorganic Chemistry 2023, 132 , 106385.
    85. Marianna Sirico, Alberto D’Angelo, Caterina Gianni, Chiara Casadei, Filippo Merloni, Ugo De Giorgi. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy. Cancers 2023, 15 (3) , 703.
    86. Sunliang Cui. Indazole as a privileged scaffold in drug discovery. 2023, 199-226.
    87. Yu Wang, Yajing Liu, Tingjie Ge, Jiechun Tang, Shihui Wang, Zhanfeng Gao, Jiaxu Chen, Jundong Xu, Ping Gong, Yanfang Zhao, Jiuyu Liu, Yunlei Hou. Based on 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474), design, synthesis and biological evaluation of novel PI3Kα selective inhibitors. Bioorganic Chemistry 2023, 130 , 106211.
    88. Maria Antonietta Occhiuzzi, Gernando Lico, Giuseppina Ioele, Michele De Luca, Antonio Garofalo, Fedora Grande. Recent advances in PI3K/PKB/mTOR inhibitors as new anticancer agents. European Journal of Medicinal Chemistry 2023, 246 , 114971.
    89. 思远 郝. Role and Future Directions of PI3K Inhibitors in Cancer Treatment. Hans Journal of Medicinal Chemistry 2023, 11 (02) , 100-107.
    90. Yeqin Yuan, Huizhi Long, Ziwei Zhou, Yuting Fu, Binyuan Jiang. PI3K–AKT-Targeting Breast Cancer Treatments: Natural Products and Synthetic Compounds. Biomolecules 2023, 13 (1) , 93.
    91. Krisida Cerma, Federico Piacentini, Luca Moscetti, Monica Barbolini, Fabio Canino, Antonio Tornincasa, Federica Caggia, Sara Cerri, Alessia Molinaro, Massimo Dominici, Claudia Omarini. Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges. Biomedicines 2023, 11 (1) , 109.
    92. Chao Ma, Yongwei Gu, Chang Liu, Xiaomeng Tang, Jianchao Yu, Dan Li, Jiyong Liu. Anti-cervical cancer effects of Compound Yangshe granule through the PI3K/AKT pathway based on network pharmacology. Journal of Ethnopharmacology 2023, 301 , 115820.
    93. Flora Cimmino, Annalaura Montella, Matilde Tirelli, Marianna Avitabile, Vito Alessandro Lasorsa, Feliciano Visconte, Sueva Cantalupo, Teresa Maiorino, Biagio De Angelis, Martina Morini, Aurora Castellano, Franco Locatelli, Mario Capasso, Achille Iolascon. FGFR1 is a potential therapeutic target in neuroblastoma. Cancer Cell International 2022, 22 (1)
    94. Xin Sun, Binliang Zhang, Leixuan Luo, Yang Yang, Bin He, Qian Zhang, Linxiao Wang, Shan Xu, Pengwu Zheng, Wufu Zhu. Design, synthesis and pharmacological evaluation of 2-arylurea-1,3,5-triazine derivative (XIN-9): A novel potent dual PI3K/mTOR inhibitor for cancer therapy. Bioorganic Chemistry 2022, 129 , 106157.
    95. Wesley D. Frey, Ashlyn Y. Anderson, Hyemin Lee, Julie B. Nguyen, Emma L. Cowles, Hua Lu, James G. Jackson, . Phosphoinositide species and filamentous actin formation mediate engulfment by senescent tumor cells. PLOS Biology 2022, 20 (10) , e3001858.
    96. Abdalla R. Mohamed, Ahmed M. El Kerdawy. A Perspective Study on the RTK, PI3K, B‐Raf, CDK and the Multi‐Protein Targeting in Medicinal Chemistry. Chemistry & Biodiversity 2022, 19 (10)
    97. Ibrahim Taha Radwan, Ahmed H.M. Elwahy, Ahmed F. Darweesh, Marwa Sharaky, Noha Bagato, Hanem Fathy Khater, Mostafa E. Salem. Design, synthesis, docking study, and anticancer evaluation of novel bis-thiazole derivatives linked to benzofuran or benzothiazole moieties as PI3k inhibitors and apoptosis inducers. Journal of Molecular Structure 2022, 1265 , 133454.
    98. Shurui Zhou, Ziyi Zhong, Yanzong Lu, Yunlong Li, Hanming Yao, Yue Zhao, Tairan Guo, Kege Yang, Yaqing Li, Shaojie Chen, Kaihong Huang, Guoda Lian. A LETM2-Regulated PI3K-Akt Signaling Axis Reveals a Prognostic and Therapeutic Target in Pancreatic Cancer. Cancers 2022, 14 (19) , 4722.
    99. Agnieszka Bochyńska, Alexander T Stenzel, Roksaneh Sayadi Boroujeni, Chao-Chung Kuo, Mirna Barsoum, Weili Liang, Philip Bussmann, Ivan G Costa, Juliane Lüscher-Firzlaff, Bernhard Lüscher. Induction of senescence upon loss of the Ash2l core subunit of H3K4 methyltransferase complexes. Nucleic Acids Research 2022, 50 (14) , 7889-7905.
    100. Christian C. Dibble, Samuel A. Barritt, Grace E. Perry, Evan C. Lien, Renee C. Geck, Sarah E. DuBois-Coyne, David Bartee, Thomas T. Zengeya, Emily B. Cohen, Min Yuan, Benjamin D. Hopkins, Jordan L. Meier, John G. Clohessy, John M. Asara, Lewis C. Cantley, Alex Toker. PI3K drives the de novo synthesis of coenzyme A from vitamin B5. Nature 2022, 608 (7921) , 192-198.
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