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Research Paper

An allosteric Akt inhibitor effectively blocks Akt signaling and tumor growth with only transient effects on glucose and insulin levels in vivo

Pages 493-503 | Published online: 01 Apr 2010

Keep up to date with the latest research on this topic with citation updates for this article.

Read on this site (2)

Niamh A Keane, Siobhan V Glavey, Janusz Krawczyk & Michael O’Dwyer. (2014) AKT as a therapeutic target in multiple myeloma. Expert Opinion on Therapeutic Targets 18:8, pages 897-915.
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SubbaRao V. Madhunapantula, Paul J. Mosca & Gavin P. Robertson. (2011) The Akt signaling pathway. Cancer Biology & Therapy 12:12, pages 1032-1049.
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Articles from other publishers (48)

Deborah S. Mortensen, Sayee G. Hegde, Sophie M. Perrin-Ninkovic, Sogole Bahmanyar, Meg McCarrick, Roy Harris, Robert Hilgraf, Branden G. S. Lee, Jeff McKie, Lisa Nadolny, John Sapienza, Alice Collette, Sarah Cox, James C. Gamez, Jennifer L. Hensel, Xuequn Helen Hua, Jim Leisten, Heather K. Raymon, Tam Tran & Rama Krishna Narla. (2023) Structure-based optimization of aminothiadiazole inhibitors of AKT. Medicinal Chemistry Research 32:7, pages 1426-1435.
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Raafat Mohamed, Aravindra Shajimoon, Rizwana Afroz, Mai Gabr, Walter G. Thomas, Peter J. Little & Danielle Kamato. (2021) Akt acts as a switch for GPCR transactivation of the TGF‐β receptor type 1. The FEBS Journal 289:9, pages 2642-2656.
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Wuming Qin, Linghui Cao & Isaac Yaw Massey. (2021) Role of PI3K/Akt signaling pathway in cardiac fibrosis. Molecular and Cellular Biochemistry 476:11, pages 4045-4059.
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Dong-Han Wi, Jong-Ho Cha & Youn-Sang Jung. (2021) Mucin in cancer: a stealth cloak for cancer cells. BMB Reports 54:7, pages 344-355.
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Laura Albentosa-González, Nereida Jimenez de Oya, Armando Arias, Pilar Clemente-Casares, Miguel Ángel Martin-Acebes, Juan Carlos Saiz, Rosario Sabariegos & Antonio Mas. (2021) Akt Kinase Intervenes in Flavivirus Replication by Interacting with Viral Protein NS5. Viruses 13:5, pages 896.
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William G. Herrick, Casey L. Kilpatrick, Melinda G. Hollingshead, Dominic Esposito, Geraldine O'Sullivan Coyne, Andrea M. Gross, Barry C. Johnson, Alice P. Chen, Brigitte C. Widemann, James H. Doroshow, Ralph E. Parchment & Apurva K. Srivastava. (2021) Isoform- and Phosphorylation-specific Multiplexed Quantitative Pharmacodynamics of Drugs Targeting PI3K and MAPK Signaling in Xenograft Models and Clinical Biopsies. Molecular Cancer Therapeutics 20:4, pages 749-760.
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Laura Albentosa-González, Rosario Sabariegos, Armando Arias, Pilar Clemente-Casares & Antonio Mas. (2021) Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication. Pathogens 10:2, pages 244.
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Meenakshisundaram Balasubramaniam, Naga Rajiv Lakkaniga, Ayed A Dera, Majed Al Fayi, Mohammed Abohashrh, Irfan Ahmad, Harish C. Chandramoorthy, Ganesan Nalini & Prasanna Rajagopalan. (2020) FCX‐146, a potent allosteric inhibitor of Akt kinase in cancer cells: Lead optimization of the second‐generation arylidene indanone scaffold. Biotechnology and Applied Biochemistry 68:1, pages 82-91.
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HASSAN M. OTIFI, MISHARI ALSHYARBA, MAJED AL FAYI, AYED A. DERA & PRASANNA RAJAGOPALAN. (2021) Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt. Oncology Research 29:3, pages 217-227.
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Ayah Abdeldayem, Yasir S. Raouf, Stefan N. Constantinescu, Richard Moriggl & Patrick T. Gunning. (2020) Advances in covalent kinase inhibitors. Chemical Society Reviews 49:9, pages 2617-2687.
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M. Iida, P.M. Harari, D.L. Wheeler & M. Toulany. (2020) Targeting AKT/PKB to improve treatment outcomes for solid tumors. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 819-820, pages 111690.
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Alison L. Kearney, Kristen C. Cooke, Dougall M. Norris, Armella Zadoorian, James R. Krycer, Daniel J. Fazakerley, James G. Burchfield & David E. James. (2019) Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes. Journal of Biological Chemistry 294:45, pages 16729-16739.
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Wilfred Lieberthal, Meiyi Tang, Mersema Abate, Mark Lusco & Jerrold S. Levine. (2019) AMPK-mediated activation of Akt protects renal tubular cells from stress-induced apoptosis in vitro and ameliorates ischemic AKI in vivo. American Journal of Physiology-Renal Physiology 317:1, pages F1-F11.
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Noreen Akhtar, Ishrat Jabeen, Nasir Jalal & Jon Antilla. (2019) Structure-based pharmacophore models to probe anticancer activity of inhibitors of protein kinase B-beta (PKB β). Chemical Biology & Drug Design 93:3, pages 325-336.
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In-Sung Song, Yu Jeong Jeong, Seung Hun Jeong, Hyoung Kyu Kim, Nam-Chul Ha, MyungGeun Shin, Kyung Soo Ko, Byoung Doo Rhee, Sungbo Shim, Sung-Wuk Jang & Jin Han. (2018) Pharmacologic inhibition of AKT leads to cell death in relapsed multiple myeloma. Cancer Letters 432, pages 205-215.
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Nick A. Iarrobino, Beant S. Gill, Mark Bernard, Rainer J. Klement, Maria Werner-Wasik & Colin E. Champ. (2018) The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small Cell Lung Cancer Patients Treated With Definitive Chemoradiation. Frontiers in Oncology 8.
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Noreen Akhtar & Ishrat Jabeen. (2016) A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain. PLOS ONE 11:12, pages e0168806.
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Margaret E. Whicker, Z. Ping Lin, Ruth Hanna, Alan C. Sartorelli & Elena S. Ratner. (2016) MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib. BMC Cancer 16:1.
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Yanmei Quan & Qiang Liu. (2016) Effect of Akti‑2 on sperm motility, capacitation and acrosome reaction in a mouse model. Biomedical Reports.
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Sadeesh K. Ramakrishnan, Huabing Zhang, Shogo Takahashi, Brook Centofanti, Sarvesh Periyasamy, Kevin Weisz, Zheng Chen, Michael D. Uhler, Liangyou Rui, Frank J. Gonzalez & Yatrik M. Shah. (2016) HIF2 α Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling. Cell Metabolism 23:3, pages 505-516.
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Ben Markman, Violeta Serra & Josep Tabernero. 2016. mTOR Inhibition for Cancer Therapy: Past, Present and Future. mTOR Inhibition for Cancer Therapy: Past, Present and Future 251 275 .
Cesar Osorio-Fuentealba & Amira Klip. (2015) Dissecting signalling by individual Akt/PKB isoforms, three steps at once. Biochemical Journal 470:2, pages e13-e16.
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A. Lan & J. Du. (2014) Potential role of Akt signaling in chronic kidney disease. Nephrology Dialysis Transplantation 30:3, pages 385-394.
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Thuy L. Phung, Wa Du, Qi Xue, Sriram Ayyaswamy, Damien Gerald, Zeus Antonello, Sokha Nhek, Carole A. Perruzzi, Isabel Acevedo, Rajesh Ramanna-Valmiki, Paul Rodriguez-Waitkus, Ladan Enayati, Marcelo L. Hochman, Dina Lev, Sandaruwan Geeganage & Laura E. Benjamin. (2015) Akt1 and Akt3 Exert Opposing Roles in the Regulation of Vascular Tumor Growth. Cancer Research 75:1, pages 40-50.
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Zhenguo Sun, Zhou Wang, Xiangyan Liu & Dong Wang. (2015) New development of inhibitors targeting the PI3K/AKT/mTOR pathway in personalized treatment of non-small-cell lung cancer. Anti-Cancer Drugs 26:1, pages 1-14.
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Frederik De Smet, Arthur Christopoulos & Peter Carmeliet. (2014) Allosteric targeting of receptor tyrosine kinases. Nature Biotechnology 32:11, pages 1113-1120.
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Andrew SpencerSung-Soo YoonSimon J. HarrisonShannon R. MorrisDeborah A. SmithRichard A. Brigandi, Jennifer GauvinRakesh Kumar, Joanna B. Opalinska & Christine Chen. (2014) The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood 124:14, pages 2190-2195.
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Joaquín Manzo-Merino, Adriana Contreras-Paredes, Elenaé Vázquez-Ulloa, Leticia Rocha-Zavaleta, Alma M. Fuentes-Gonzalez & Marcela Lizano. (2014) The Role of Signaling Pathways in Cervical Cancer and Molecular Therapeutic Targets. Archives of Medical Research 45:7, pages 525-539.
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Yassine Rechoum, Daniela Rovito, Domenico Iacopetta, Ines Barone, Sebastiano Andò, Nancy L. Weigel, Bert W. O’Malley, Powel H. Brown & Suzanne A. W. Fuqua. (2014) AR collaborates with ERα in aromatase inhibitor-resistant breast cancer. Breast Cancer Research and Treatment 147:3, pages 473-485.
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Sivan M. Bokobza, Yanyan Jiang, Anika M. Weber, Aoife M. Devery & Anderson J. Ryan. (2014) Combining AKT inhibition with chloroquine and gefitinib prevents compensatory autophagy and induces cell death in EGFR mutated NSCLC cells. Oncotarget 5:13, pages 4765-4778.
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N Panupinthu, S Yu, D Zhang, F Zhang, M Gagea, Y Lu, J R Grandis, S E Dunn, H Y Lee & G B Mills. (2013) Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer. Oncogene 33:22, pages 2846-2856.
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Oya Gursoy Yilmaz, Elif Ozkirimli Olmez & Kutlu O. Ulgen. (2014) Targeting the Akt1 allosteric site to identify novel scaffolds through virtual screening. Computational Biology and Chemistry 48, pages 1-13.
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Florian Ewald, Nicole Grabinski, Astrid Grottke, Sabine Windhorst, Dominik Nörz, Lisa Carstensen, Katharina Staufer, Bianca T. Hofmann, Frank Diehl, Kerstin David, Udo Schumacher, Björn Nashan & Manfred Jücker. (2013) Combined targeting of AKT and mTOR using MK-2206 and RAD001 is synergistic in the treatment of cholangiocarcinoma. International Journal of Cancer 133:9, pages 2065-2076.
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Holger SteinbrennerBodo SpeckmannHelmut Sies. (2013) Toward Understanding Success and Failures in the Use of Selenium for Cancer Prevention. Antioxidants & Redox Signaling 19:2, pages 181-191.
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Evangelos Sarris, Muhammad Saif & Kostas Syrigos. (2012) The Biological Role of PI3K Pathway in Lung Cancer. Pharmaceuticals 5:11, pages 1236-1264.
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Naveen Sharma, Edward B. Arias, Donel A. Sequea & Gregory D. Cartee. (2012) Preventing the calorie restriction-induced increase in insulin-stimulated Akt2 phosphorylation eliminates calorie restriction's effect on glucose uptake in skeletal muscle. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1822:11, pages 1735-1740.
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Yu-Chiang Lai, Yang Liu, Roxane Jacobs & Mark H. Rider. (2012) A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle. Biochemical Journal 447:1, pages 137-147.
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P. Y. Wen, E. Q. Lee, D. A. Reardon, K. L. Ligon & W. K. Alfred Yung. (2012) Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro-Oncology 14:7, pages 819-829.
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Kui LinJie LinWen-I WuJoshua BallardBrian B. LeeSusan L. GloorGuy P. A. VigersTony H. MoralesLori S. FriedmanNicholas SkeltonBarbara J. Brandhuber. (2012) An ATP-Site On-Off Switch That Restricts Phosphatase Accessibility of Akt. Science Signaling 5:223.
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Justin Hall, Ann Aulabaugh, Francis Rajamohan, Shenping Liu, Neelu Kaila, Zhao-Kui Wan, Mark Ryan, Rachelle Magyar & Xiayang Qiu. (2012) Biophysical and Mechanistic Insights into Novel Allosteric Inhibitor of Spleen Tyrosine Kinase. Journal of Biological Chemistry 287:10, pages 7717-7727.
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Brooke M. Emerling & Argun Akcakanat. (2011) Targeting PI3K/mTOR Signaling in Cancer. Cancer Research 71:24, pages 7351-7359.
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Timothy A. YapLi YanAmita PatnaikIvy FearenDavid OlmosKyriakos PapadopoulosRichard D. BairdLiliana DelgadoAdekemi TaylorLisa LupinacciRuth RiisnaesLorna L. PopeSimon P. HeatonGeorge ThomasMichelle D. GarrettDaniel M. SullivanJohann S. de BonoAnthony W. Tolcher. (2011) First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors. Journal of Clinical Oncology 29:35, pages 4688-4695.
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Anna Wojtalla & Alexandre Arcaro. (2011) Targeting phosphoinositide 3-kinase signalling in lung cancer. Critical Reviews in Oncology/Hematology 80:2, pages 278-290.
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Ingeborg Hers, Emma E. Vincent & Jeremy M. Tavaré. (2011) Akt signalling in health and disease. Cellular Signalling 23:10, pages 1515-1527.
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Christos Polytarchou, Dimitrios Iliopoulos, Maria Hatziapostolou, Filippos Kottakis, Ioanna Maroulakou, Kevin Struhl & Philip N. Tsichlis. (2011) Akt2 Regulates All Akt Isoforms and Promotes Resistance to Hypoxia through Induction of miR-21 upon Oxygen Deprivation. Cancer Research 71:13, pages 4720-4731.
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Stacey A. Santi, Alison C. Douglas & Hoyun Lee. (2010) The Akt isoforms, their unique functions and potential as anticancer therapeutic targets. BioMolecular Concepts 1:5-6, pages 389-401.
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Shi-Xiong Tan, Yvonne Ng & David E. James. (2010) Akt inhibitors reduce glucose uptake independently of their effects on Akt. Biochemical Journal 432:1, pages 191-198.
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Qing-Bai She, Ensar Halilovic, Qing Ye, Wei Zhen, Senji Shirasawa, Takehiko Sasazuki, David B. Solit & Neal Rosen. (2010) 4E-BP1 Is a Key Effector of the Oncogenic Activation of the AKT and ERK Signaling Pathways that Integrates Their Function in Tumors. Cancer Cell 18:1, pages 39-51.
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