4ekl › Citations

An ATP-site on-off switch that restricts phosphatase accessibility of Akt.

Lin K, Lin J, Wu WI, Ballard J, Lee BB, Gloor SL, Vigers GP, Morales TH, Friedman LS, Skelton N, Brandhuber BJ
Sci Signal 5 ra37 (2012)
Cited: 120 times
EuropePMC logo PMID: 22569334

Abstract

The protein serine-threonine kinase Akt undergoes a substantial conformational change upon activation, which is induced by the phosphorylation of two critical regulatory residues, threonine 308 and serine 473. Paradoxically, treating cells with adenosine 5'-triphosphate (ATP)-competitive inhibitors of Akt results in increased phosphorylation of both residues. We show that binding of ATP-competitive inhibitors stabilized a conformation in which both phosphorylated sites were inaccessible to phosphatases. ATP binding also produced this protection of the phosphorylated sites, whereas interaction with its hydrolysis product adenosine 5'-diphosphate (ADP) or allosteric Akt inhibitors resulted in increased accessibility of these phosphorylated residues. ATP-competitive inhibitors mimicked ATP by targeting active Akt. Forms of Akt activated by an oncogenic mutation or myristoylation were more potently inhibited by the ATP-competitive inhibitors than was wild-type Akt. These data support a new model of kinase regulation, wherein nucleotides modulate an on-off switch in Akt through conformational changes, which is disrupted by ATP-competitive inhibitors.

Reviews - 4ekl mentioned but not cited (2)

  1. Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein. Primavera E, Palazzotti D, Barreca ML, Astolfi A. Pharmaceuticals (Basel) 16 993 (2023)
  2. Drug Discovery of Plausible Lead Natural Compounds That Target the Insulin Signaling Pathway: Bioinformatics Approaches. Shanak S, Bassalat N, Barghash A, Kadan S, Ardah M, Zaid H. Evid Based Complement Alternat Med 2022 2832889 (2022)

Articles - 4ekl mentioned but not cited (38)

  1. Structural protein-ligand interaction fingerprints (SPLIF) for structure-based virtual screening: method and benchmark study. Da C, Kireev D. J Chem Inf Model 54 2555-2561 (2014)
  2. Discovery of an AKT Degrader with Prolonged Inhibition of Downstream Signaling. You I, Erickson EC, Donovan KA, Eleuteri NA, Fischer ES, Gray NS, Toker A. Cell Chem Biol 27 66-73.e7 (2020)
  3. A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity. Kostaras E, Kaserer T, Lazaro G, Heuss SF, Hussain A, Casado P, Hayes A, Yandim C, Palaskas N, Yu Y, Schwartz B, Raynaud F, Chung YL, Cutillas PR, Vivanco I. Br J Cancer 123 542-555 (2020)
  4. Peperomin E reactivates silenced tumor suppressor genes in lung cancer cells by inhibition of DNA methyltransferase. Wang XZ, Cheng Y, Wang KL, Liu R, Yang XL, Wen HM, Chai C, Liang JY, Wu H. Cancer Sci 107 1506-1519 (2016)
  5. Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology. Wang W, Wang S, Liu T, Ma Y, Huang S, Lei L, Wen A, Ding Y. Front Pharmacol 11 694 (2020)
  6. Utilizing network pharmacology and molecular docking to explore the underlying mechanism of Guizhi Fuling Wan in treating endometriosis. Wang H, Zhou G, Zhuang M, Wang W, Fu X. PeerJ 9 e11087 (2021)
  7. Design, Synthesis, and Evaluation of Potent, Selective, and Bioavailable AKT Kinase Degraders. Yu X, Xu J, Xie L, Wang L, Shen Y, Cahuzac KM, Chen X, Liu J, Parsons RE, Jin J. J Med Chem 64 18054-18081 (2021)
  8. Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery. Xie Y, Mu C, Kazybay B, Sun Q, Kutzhanova A, Nazarbek G, Xu N, Nurtay L, Wang Q, Amin A, Li X. Drug Deliv 28 2187-2197 (2021)
  9. Pharmacological Mechanisms Underlying the Hepatoprotective Effects of Ecliptae herba on Hepatocellular Carcinoma. Pan B, Pan W, Lu Z, Xia C. Evid Based Complement Alternat Med 2021 5591402 (2021)
  10. Design, synthesis and pharmaco-toxicological assessment of 5-mercapto-1,2,4-triazole derivatives with antibacterial and antiproliferative activity. Mioc M, Soica C, Bercean V, Avram S, Balan-Porcarasu M, Coricovac D, Ghiulai R, Muntean D, Andrica F, Dehelean C, Spandidos DA, Tsatsakis AM, Kurunczi L. Int. J. Oncol. (2017)
  11. Mechanisms of Spica Prunellae against thyroid-associated Ophthalmopathy based on network pharmacology and molecular docking. Zhang Y, Li X, Guo C, Dong J, Liao L. BMC Complement Med Ther 20 229 (2020)
  12. The synthesis of novel thioderivative chalcones and their influence on NF-κB, STAT3 and NRF2 signaling pathways in colorectal cancer cells. Papierska K, Krajka-Kuźniak V, Kleszcz R, Stefański T, Kurczab R, Kubicki M. Sci Rep 12 14915 (2022)
  13. A Network Pharmacology Approach to Estimate Potential Targets of the Active Ingredients of Epimedium for Alleviating Mild Cognitive Impairment and Treating Alzheimer's Disease. Gao X, Li S, Cong C, Wang Y, Xu L. Evid Based Complement Alternat Med 2021 2302680 (2021)
  14. Coumarin Derivative N6 as a Novel anti-hantavirus Infection Agent Targeting AKT. Li Z, Wang F, Liu Y, Zhai D, Zhang X, Ying Q, Jia M, Xue X, Meng J, Li J, Wu X, Li M. Front Pharmacol 12 745646 (2021)
  15. Investigating pharmacological mechanisms of andrographolide on non-alcoholic steatohepatitis (NASH): A bioinformatics approach of network pharmacology. Li L, Li SH, Jiang JP, Liu C, Ji LL. Chin Herb Med 13 342-350 (2021)
  16. Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology. Li M, Zhao J, Tang Q, Zhang Q, Wang Y, Zhang J, Hao Y, Bai X, Lu Z. J Cell Mol Med 25 8490-8503 (2021)
  17. Mechanism of Tetrandrine Against Endometrial Cancer Based on Network Pharmacology. Shang W, Zhang J, Song H, Zhu S, Zhang A, Hua Y, Han S, Fu Y. Drug Des Devel Ther 15 2907-2919 (2021)
  18. Network pharmacology study on the mechanism of Qiangzhifang in the treatment of panic disorder. Zhao R, Liu P, Song A, Liu J, Chu Q, Liu Y, Jiang Y, Dong C, Shi H, Yan Z. Ann Transl Med 9 1350 (2021)
  19. Norcycloartocarpin targets Akt and suppresses Akt-dependent survival and epithelial-mesenchymal transition in lung cancer cells. Nonpanya N, Sanookpan K, Joyjamras K, Wichadakul D, Sritularak B, Chaotham C, Chanvorachote P. PLoS One 16 e0254929 (2021)
  20. Targeting allosteric site of AKT by 5,7-dimethoxy-1,4-phenanthrenequinone suppresses neutrophilic inflammation. Chen PJ, Ko IL, Lee CL, Hu HC, Chang FR, Wu YC, Leu YL, Wu CC, Lin CY, Pan CY, Tsai YF, Hwang TL. EBioMedicine 40 528-540 (2019)
  21. In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway. Li Z, Wang F, Ying Q, Kong D, Zhang X, Dong Y, Liu Y, Zhai D, Chen Z, Jia M, Xue X, Li M, Wu X. Front Microbiol 13 880258 (2022)
  22. Bag-1 stimulates Bad phosphorylation through activation of Akt and Raf kinases to mediate cell survival in breast cancer. Kizilboga T, Baskale EA, Yildiz J, Akcay IM, Zemheri E, Can ND, Ozden C, Demir S, Ezberci F, Dinler-Doganay G. BMC Cancer 19 1254 (2019)
  23. Deciphering the Active Compounds and Mechanisms of HSBDF for Treating ALI via Integrating Chemical Bioinformatics Analysis. Wang Y, Jin X, Fan Q, Li C, Zhang M, Wang Y, Wu Q, Li J, Liu X, Wang S, Wang Y, Li L, Ling J, Li C, Wang Q, Liu Y. Front Pharmacol 13 879268 (2022)
  24. Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q exactive focus mass spectrometry, network pharmacology, and molecular docking. Hui R, Lintao Z, Kai G, Yuanyuan Y, Xiaomin C, Jing HU, Zhiyong C, Ye LI. J Tradit Chin Med 43 1209-1218 (2023)
  25. Dose Optimization of Anxiolytic Compounds Group in Valeriana jatamansi Jones and Mechanism Exploration by Integrating Network Pharmacology and Metabolomics Analysis. Zhao C, Wei X, Guo J, Ding Y, Luo J, Yang X, Li J, Wan G, Yu J, Shi J. Brain Sci 12 589 (2022)
  26. From Serendipity to Rational Identification of the 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one Core as a New Chemotype of AKT1 Inhibitors for Acute Myeloid Leukemia. Astolfi A, Milano F, Palazzotti D, Brea J, Pismataro MC, Morlando M, Tabarrini O, Loza MI, Massari S, Martelli MP, Barreca ML. Pharmaceutics 14 2295 (2022)
  27. Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation. Hu J, Feng Y, Li B, Wang F, Qian Q, Tian W, Niu L, Wang X. PeerJ 11 e15948 (2023)
  28. Molecular Mechanism of Salvia miltiorrhiza Bunge in Treating Cerebral Infarction. Ye X, Liu J, Yuan X, Yang S, Huang Y, Chen Y. Evid Based Complement Alternat Med 2022 5992394 (2022)
  29. Molecular mechanism underlying the anti-inflammatory effects of volatile components of Ligularia fischeri (Ledeb) Turcz based on network pharmacology. Huang X, Gao Y, Xu F, Fan D, Liang Y, Wang X, Wu H. BMC Complement Med Ther 20 109 (2020)
  30. Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury. Xiao S, Liu L, Sun Z, Liu X, Xu J, Guo Z, Yin X, Liao F, Xu J, You Y, Zhang T. Front Pharmacol 13 891889 (2022)
  31. Network Pharmacology and Molecular Docking Reveal the Mechanism of Isodon ternifolius (D. Don) Kudo Against Liver Fibrosis. Deng J, Qin L, Zhou Z. Drug Des Devel Ther 17 2335-2351 (2023)
  32. Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma. Mir WR, Bhat BA, Kumar A, Dhiman R, Alkhanani M, Almilaibary A, Dar MY, Ganie SA, Mir MA. Front Pharmacol 14 1135898 (2023)
  33. Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway. Lei W, Yan Y, Ma Y, Jiang M, Zhang B, Zhang H, Li Y. Front Pharmacol 13 905092 (2022)
  34. Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells. Aung TM, Silsirivanit A, Jusakul A, Chan-On W, Proungvitaya T, Roytrakul S, Proungvitaya S. Cancer Genomics Proteomics 19 490-502 (2022)
  35. Protective effect of Cordyceps sinensis against diabetic kidney disease through promoting proliferation and inhibiting apoptosis of renal proximal tubular cells. Zhang Y, Xu L, Lu Y, Zhang J, Yang M, Tian Y, Dong J, Liao L. BMC Complement Med Ther 23 109 (2023)
  36. Pyrimidine-5-carbonitrile based potential anticancer agents as apoptosis inducers through PI3K/AKT axis inhibition in leukaemia K562. El-Dydamony NM, Abdelnaby RM, Abdelhady R, Ali O, Fahmy MI, R Fakhr Eldeen R, Helwa AA. J Enzyme Inhib Med Chem 37 895-911 (2022)
  37. Structure-Based Profiling of Potential Phytomolecules with AKT1 a Key Cancer Drug Target. Mirza Z, Karim S. Molecules 28 2597 (2023)
  38. The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule: Targeting cancer cells signaling PI3K and AKT kinase pathway. Gupta KK, Sharma KK, Chandra H, Panwar H, Bhardwaj N, Altwaijry NA, Alsfouk AA, Dlamini Z, Afzal O, Altamimi ASA, Khan S, Mishra AP. Front Oncol 12 950835 (2022)


Reviews citing this publication (13)

  1. AKT/PKB Signaling: Navigating the Network. Manning BD, Toker A. Cell 169 381-405 (2017)
  2. Purinergic signalling and cancer. Burnstock G, Di Virgilio F. Purinergic Signal. 9 491-540 (2013)
  3. Protein kinase C pharmacology: refining the toolbox. Wu-Zhang AX, Newton AC. Biochem. J. 452 195-209 (2013)
  4. Ten things you should know about protein kinases: IUPHAR Review 14. Fabbro D, Cowan-Jacob SW, Moebitz H. Br. J. Pharmacol. 172 2675-2700 (2015)
  5. AKT as a therapeutic target in multiple myeloma. Keane NA, Glavey SV, Krawczyk J, O'Dwyer M. Expert Opin. Ther. Targets 18 897-915 (2014)
  6. Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products. Iksen, Pothongsrisit S, Pongrakhananon V. Molecules 26 4100 (2021)
  7. Kinase inhibitors as potential agents in the treatment of multiple myeloma. Abramson HN. Oncotarget 7 81926-81968 (2016)
  8. Control of Akt activity and substrate phosphorylation in cells. Yudushkin I. IUBMB Life 72 1115-1125 (2020)
  9. Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K. Yudushkin I. Biomolecules 9 (2019)
  10. Inhibitors in AKTion: ATP-competitive vs allosteric. Lazaro G, Kostaras E, Vivanco I. Biochem Soc Trans 48 933-943 (2020)
  11. Lipid-dependent Akt-ivity: where, when, and how. Siess KM, Leonard TA. Biochem. Soc. Trans. 47 897-908 (2019)
  12. Signaling pathway profiling using reverse-phase protein array and its clinical applications. Masuda M, Yamada T. Expert Rev Proteomics 14 607-615 (2017)
  13. The Pasteur's Dictum: Nitrogen Promotes Growth and Oxygen Reduces the Need for Sugar. Vadlakonda L, Reddy VD, Pasupuleti M, Reddanna P. Front Oncol 4 51 (2014)

Articles citing this publication (67)

  1. The Paradox of Akt-mTOR Interactions. Vadlakonda L, Dash A, Pasupuleti M, Anil Kumar K, Reddanna P. Front Oncol 3 165 (2013)
  2. Selective insulin resistance in adipocytes. Tan SX, Fisher-Wellman KH, Fazakerley DJ, Ng Y, Pant H, Li J, Meoli CC, Coster AC, Stöckli J, James DE. J. Biol. Chem. 290 11337-11348 (2015)
  3. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. Cancer Discov 7 102-113 (2017)
  4. PI(3,4,5)P3 Engagement Restricts Akt Activity to Cellular Membranes. Ebner M, Lučić I, Leonard TA, Yudushkin I. Mol. Cell 65 416-431.e6 (2017)
  5. Phosphoproteomic analysis implicates the mTORC2-FoxO1 axis in VEGF signaling and feedback activation of receptor tyrosine kinases. Zhuang G, Yu K, Jiang Z, Chung A, Yao J, Ha C, Toy K, Soriano R, Haley B, Blackwood E, Sampath D, Bais C, Lill JR, Ferrara N. Sci Signal 6 ra25 (2013)
  6. InterAKTions with FKBPs--mutational and pharmacological exploration. Fabian AK, März A, Neimanis S, Biondi RM, Kozany C, Hausch F. PLoS ONE 8 e57508 (2013)
  7. Ligand binding to the AMP-activated protein kinase active site mediates protection of the activation loop from dephosphorylation. Chandrashekarappa DG, McCartney RR, Schmidt MC. J. Biol. Chem. 288 89-98 (2013)
  8. The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation. Lu S, Deng R, Jiang H, Song H, Li S, Shen Q, Huang W, Nussinov R, Yu J, Zhang J. Structure 23 1725-1734 (2015)
  9. Linking phenotype to kinase: identification of a novel benzoxaborole hinge-binding motif for kinase inhibition and development of high-potency rho kinase inhibitors. Akama T, Dong C, Virtucio C, Sullivan D, Zhou Y, Zhang YK, Rock F, Freund Y, Liu L, Bu W, Wu A, Fan XQ, Jarnagin K. J Pharmacol Exp Ther 347 615-625 (2013)
  10. Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway. Trefely S, Khoo PS, Krycer JR, Chaudhuri R, Fazakerley DJ, Parker BL, Sultani G, Lee J, Stephan JP, Torres E, Jung K, Kuijl C, James DE, Junutula JR, Stöckli J. J. Biol. Chem. 290 25834-25846 (2015)
  11. Novel quantitative autophagy analysis by organelle flow cytometry after cell sonication. Degtyarev M, Reichelt M, Lin K. PLoS ONE 9 e87707 (2014)
  12. Candidate tumor suppressor and pVHL partner Jade-1 binds and inhibits AKT in renal cell carcinoma. Zeng L, Bai M, Mittal AK, El-Jouni W, Zhou J, Cohen DM, Zhou MI, Cohen HT. Cancer Res. 73 5371-5380 (2013)
  13. Conformational sampling of membranes by Akt controls its activation and inactivation. Lučić I, Rathinaswamy MK, Truebestein L, Hamelin DJ, Burke JE, Leonard TA. Proc. Natl. Acad. Sci. U.S.A. 115 E3940-E3949 (2018)
  14. Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer. Shi Z, Wulfkuhle J, Nowicka M, Gallagher RI, Saura C, Nuciforo PG, Calvo I, Andersen J, Passos-Coelho JL, Gil-Gil MJ, Bermejo B, Pratt DA, Ciruelos EM, Villagrasa P, Wongchenko MJ, Petricoin EF, Oliveira M, Isakoff SJ. Clin Cancer Res 28 993-1003 (2022)
  15. A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway. Cheraghchi-Bashi A, Parker CA, Curry E, Salazar JF, Gungor H, Saleem A, Cunnea P, Rama N, Salinas C, Mills GB, Morris SR, Kumar R, Gabra H, Stronach EA. Oncotarget 6 41736-41749 (2015)
  16. Protein kinase d inhibitors uncouple phosphorylation from activity by promoting agonist-dependent activation loop phosphorylation. Kunkel MT, Newton AC. Chem. Biol. 22 98-106 (2015)
  17. Uncaging akt. Humphrey SJ, James DE. Sci Signal 5 pe20 (2012)
  18. PI3K drives the de novo synthesis of coenzyme A from vitamin B5. Dibble CC, Barritt SA, Perry GE, Lien EC, Geck RC, DuBois-Coyne SE, Bartee D, Zengeya TT, Cohen EB, Yuan M, Hopkins BD, Meier JL, Clohessy JG, Asara JM, Cantley LC, Toker A. Nature 608 192-198 (2022)
  19. Probing Protein-Membrane Interactions and Dynamics Using Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS). Stariha JTB, Hoffmann RM, Hamelin DJ, Burke JE. Methods Mol Biol 2263 465-485 (2021)
  20. The Akt DUBbed InAktive. Lin K. Sci Signal 6 pe1 (2013)
  21. Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis. Chu N, Salguero AL, Liu AZ, Chen Z, Dempsey DR, Ficarro SB, Alexander WM, Marto JA, Li Y, Amzel LM, Gabelli SB, Cole PA. Cell 174 897-907.e14 (2018)
  22. Combining ligand- and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1. Mahajan P, Wadhwa B, Barik MR, Malik F, Nargotra A. Mol Divers 24 45-60 (2020)
  23. AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B. Xu J, Yu X, Martin TC, Bansal A, Cheung K, Lubin A, Stratikopoulos E, Cahuzac KM, Wang L, Xie L, Zhou R, Shen Y, Wu X, Yao S, Qiao R, Poulikakos PI, Chen X, Liu J, Jin J, Parsons R. Cancer Discov 11 3064-3089 (2021)
  24. Efficient and cost effective production of active-form human PKB using silkworm larvae. Maesaki R, Satoh R, Taoka M, Kanaba T, Asano T, Fujita C, Fujiwara T, Ito Y, Isobe T, Hakoshima T, Maenaka K, Mishima M. Sci Rep 4 6016 (2014)
  25. Structure of autoinhibited Akt1 reveals mechanism of PIP3-mediated activation. Truebestein L, Hornegger H, Anrather D, Hartl M, Fleming KD, Stariha JTB, Pardon E, Steyaert J, Burke JE, Leonard TA. Proc Natl Acad Sci U S A 118 e2101496118 (2021)
  26. mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif. Baffi TR, Lordén G, Wozniak JM, Feichtner A, Yeung W, Kornev AP, King CC, Del Rio JC, Limaye AJ, Bogomolovas J, Gould CM, Chen J, Kennedy EJ, Kannan N, Gonzalez DJ, Stefan E, Taylor SS, Newton AC. Sci Signal 14 eabe4509 (2021)
  27. Akt kinase C-terminal modifications control activation loop dephosphorylation and enhance insulin response. Chan TO, Zhang J, Tiegs BC, Blumhof B, Yan L, Keny N, Penny M, Li X, Pascal JM, Armen RS, Rodeck U, Penn RB. Biochem. J. 471 37-51 (2015)
  28. Did we get pasteur, warburg, and crabtree on a right note? Vadlakonda L, Dash A, Pasupuleti M, Anil Kumar K, Reddanna P. Front Oncol 3 186 (2013)
  29. In vitro reconstitution of Sgk3 activation by phosphatidylinositol 3-phosphate. Pokorny D, Truebestein L, Fleming KD, Burke JE, Leonard TA. J Biol Chem 297 100919 (2021)
  30. Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis. Sun L, Huang Y, Liu Y, Zhao Y, He X, Zhang L, Wang F, Zhang Y. Cell Death Dis 9 911 (2018)
  31. Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study. Magrini TD, dos Santos NV, Milazzotto MP, Cerchiaro G, da Silva Martinho H. J Biomed Opt 17 101516 (2012)
  32. TAPP Adaptors Control B Cell Metabolism by Modulating the Phosphatidylinositol 3-Kinase Signaling Pathway: A Novel Regulatory Circuit Preventing Autoimmunity. Jayachandran N, Mejia EM, Sheikholeslami K, Sher AA, Hou S, Hatch GM, Marshall AJ. J. Immunol. 201 406-416 (2018)
  33. Akt Is S-Palmitoylated: A New Layer of Regulation for Akt. Blaustein M, Piegari E, Martínez Calejman C, Vila A, Amante A, Manese MV, Zeida A, Abrami L, Veggetti M, Guertin DA, van der Goot FG, Corvi MM, Colman-Lerner A. Front Cell Dev Biol 9 626404 (2021)
  34. Bioinformatics Study of Sea Cucumber Peptides as Antibreast Cancer Through Inhibiting the Activity of Overexpressed Protein (EGFR, PI3K, AKT1, and CDK4). Wargasetia TL, Ratnawati H, Widodo N, Widyananda MH. Cancer Inform 20 11769351211031864 (2021)
  35. Characterization of exposure-response relationships of ipatasertib in patients with metastatic castration-resistant prostate cancer in the IPATential150 study. Kotani N, Wilkins JJ, Wade JR, Dang S, Sutaria DS, Yoshida K, Sundrani S, Ding H, Garcia J, Hinton H, Sane R, Chanu P. Cancer Chemother Pharmacol 90 511-521 (2022)
  36. Curcumin Decreases Viability and Inhibits Proliferation of Imatinib-Sensitive and Imatinib-Resistant Chronic Myeloid Leukemia Cell Lines. Bilajac E, Mahmutović L, Glamočlija U, Osmanović A, Hromić-Jahjefendić A, Tambuwala MM, Suljagić M. Metabolites 13 58 (2022)
  37. HER3 Differentiates Basal From Claudin Type Triple Negative Breast Cancer and Contributes to Drug and Microenvironmental Induced Resistance. Sinevici N, Ataeinia B, Zehnder V, Lin K, Grove L, Heidari P, Mahmood U. Front Oncol 10 554704 (2020)
  38. Ipatasertib exhibits anti‑tumorigenic effects and enhances sensitivity to paclitaxel in endometrial cancer in vitro and in vivo. O'Donnell J, Zhao Z, Buckingham L, Hao T, Suo H, Zhang X, Fan Y, John C, Deng B, Shen X, Sun W, Secord AA, Zhou C, Bae-Jump VL. Int J Oncol 63 103 (2023)
  39. Microsecond molecular dynamics simulations provide insight into the ATP-competitive inhibitor-induced allosteric protection of Akt kinase phosphorylation. Mou L, Cui T, Liu W, Zhang H, Cai Z, Lu S, Gao G. Chem Biol Drug Des 89 723-731 (2017)
  40. Novel Allosteric Inhibitor-Derived AKT Proteolysis Targeting Chimeras (PROTACs) Enable Potent and Selective AKT Degradation in KRAS/BRAF Mutant Cells. Yu X, Xu J, Cahuzac KM, Xie L, Shen Y, Chen X, Liu J, Parsons RE, Jin J. J Med Chem 65 14237-14260 (2022)
  41. Novel Synthetic Derivative of Renieramycin T Right-Half Analog Induces Apoptosis and Inhibits Cancer Stem Cells via Targeting the Akt Signal in Lung Cancer Cells. Petsri K, Yokoya M, Racha S, Thongsom S, Thepthanee C, Innets B, Ei ZZ, Hotta D, Zou H, Chanvorachote P. Int J Mol Sci 24 5345 (2023)
  42. Olfactory Bulb Proteomics Reveals Widespread Proteostatic Disturbances in Mixed Dementia and Guides for Potential Serum Biomarkers to Discriminate Alzheimer Disease and Mixed Dementia Phenotypes. Lachén-Montes M, Íñigo-Marco I, Cartas-Cejudo P, Fernández-Irigoyen J, Santamaría E. J Pers Med 11 503 (2021)
  43. PDK1:PKCα heterodimer association-dissociation dynamics in single-molecule diffusion tracks on a target membrane. Gordon MT, Ziemba BP, Falke JJ. Biophys J 122 2301-2310 (2023)
  44. Pharmacokinetics of Ipatasertib in Subjects With Hepatic Impairment Using 2 Methods of Classification of Hepatic Function. Sane R, Malhi V, Sutaria DS, Cho E, Twomey P, Craggs C, Wang J, Harris A, Musib L. J Clin Pharmacol 62 171-181 (2022)
  45. Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple-negative breast cancer. Wright TD, Raybuck C, Bhatt A, Monlish D, Chakrabarty S, Wendekier K, Gartland N, Gupta M, Burow ME, Flaherty PT, Cavanaugh JE. J. Cell. Biochem. 121 1156-1168 (2020)
  46. Single-molecule studies reveal regulatory interactions between master kinases PDK1, AKT1, and PKC. Gordon MT, Ziemba BP, Falke JJ. Biophys J 120 5657-5673 (2021)
  47. Studies on Biological and Molecular Effects of Small-Molecule Kinase Inhibitors on Human Glioblastoma Cells and Organotypic Brain Slices. Hörnschemeyer J, Kirschstein T, Reichart G, Sasse C, Venus J, Einsle A, Porath K, Linnebacher M, Köhling R, Lange F. Life (Basel) 12 1258 (2022)
  48. 2-Phenylquinazolinones as dual-activity tankyrase-kinase inhibitors. Nkizinkiko Y, Desantis J, Koivunen J, Haikarainen T, Murthy S, Sancineto L, Massari S, Ianni F, Obaji E, Loza MI, Pihlajaniemi T, Brea J, Tabarrini O, Lehtiö L. Sci Rep 8 1680 (2018)
  49. A tripartite cooperative mechanism confers resistance of the protein kinase A catalytic subunit to dephosphorylation. Chan TO, Armen RS, Yadav S, Shah S, Zhang J, Tiegs BC, Keny N, Blumhof B, Deshpande DA, Rodeck U, Penn RB. J Biol Chem 295 3316-3329 (2020)
  50. AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay. Cho H, Abshire ET, Popp MW, Pröschel C, Schwartz JL, Yeo GW, Maquat LE. Mol Cell 82 2779-2796.e10 (2022)
  51. AKT mutant allele-specific activation dictates pharmacologic sensitivities. Shrestha Bhattarai T, Shamu T, Gorelick AN, Chang MT, Chakravarty D, Gavrila EI, Donoghue MTA, Gao J, Patel S, Gao SP, Reynolds MH, Phillips SM, Soumerai T, Abida W, Hyman DM, Schram AM, Solit DB, Smyth LM, Taylor BS. Nat Commun 13 2111 (2022)
  52. Activation of Insulin Signaling in Adipocytes and Myotubes by Sarcopoterium Spinosum Extract. Ben-Shachar M, Rozenberg K, Skalka N, Wollman A, Michlin M, Rosenzweig T. Nutrients 11 (2019)
  53. Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-HER2 therapy in PIK3CA-mutant HER2-positive breast cancer cells. Fujimoto Y, Morita TY, Ohashi A, Haeno H, Hakozaki Y, Fujii M, Kashima Y, Kobayashi SS, Mukohara T. Sci Rep 10 21762 (2020)
  54. Distinct resistance mechanisms arise to allosteric vs. ATP-competitive AKT inhibitors. Savill KMZ, Lee BB, Oeh J, Lin J, Lin E, Chung WJ, Young A, Chen W, Miś M, Mesh K, Eastham J, Gnad F, Jiang Z, Stawiski EW, Haley B, Daemen A, Wang X, Koeppen H, Modrusan Z, Martin SE, Sampath D, Lin K. Nat Commun 13 2057 (2022)
  55. EBP2, a novel NPM-ALK-interacting protein in the nucleolus, contributes to the proliferation of ALCL cells by regulating tumor suppressor p53. Uchihara Y, Tago K, Tamura H, Funakoshi-Tago M. Mol Oncol 15 167-194 (2021)
  56. Effect of mitochondrially targeted carboxy proxyl nitroxide on Akt-mediated survival in Daudi cells: Significance of a dual mode of action. Variar G, Pant T, Singh A, Ravichandran A, Swami S, Kalyanaraman B, Dhanasekaran A. PLoS ONE 12 e0174546 (2017)
  57. Fake Inhibitors: AMPK Activation Trumps Inhibition. Langendorf CG, Scott JW, Kemp BE. Cell Chem Biol 24 775-777 (2017)
  58. Functional characterization of the PI3K/AKT/MTOR signaling pathway for targeted therapy in B-precursor acute lymphoblastic leukemia. Grüninger PK, Uhl F, Herzog H, Gentile G, Andrade-Martinez M, Schmidt T, Han K, Morgens DW, Bassik MC, Cleary ML, Gorka O, Zeiser R, Groß O, Duque-Afonso J. Cancer Gene Ther 29 1751-1760 (2022)
  59. Galvanotactic Migration of Glioblastoma and Brain Metastases Cells. Lange F, Venus J, Shams Esfand Abady D, Porath K, Einsle A, Sellmann T, Neubert V, Reichart G, Linnebacher M, Köhling R, Kirschstein T. Life (Basel) 12 580 (2022)
  60. Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis. Kempska J, Oliveira-Ferrer L, Grottke A, Qi M, Alawi M, Meyer F, Borgmann K, Hamester F, Eylmann K, Rossberg M, Smit DJ, Jücker M, Laakmann E, Witzel I, Schmalfeldt B, Müller V, Legler K. Front Oncol 13 1129682 (2023)
  61. Molecular docking appraisal of Dysphania ambrosioides phytochemicals as potential inhibitor of a key triple-negative breast cancer driver gene. Anifowose LO, Paimo OK, Adegboyega FN, Ogunyemi OM, Akano RO, Hammad SF, Ghazy MA. In Silico Pharmacol 11 15 (2023)
  62. New pyrimidine-N-β-D-glucosides: synthesis, biological evaluation, and molecular docking investigations. Kahriman N, Peker K, Serdaroğlu V, Aydin A, Türkmenoğlu B, Usta A, Yayli N. Turk J Chem 47 476-494 (2023)
  63. Oridonin inhibits aberrant AKT activation in breast cancer. Sun B, Wang G, Liu H, Liu P, Twal WO, Cheung H, Carroll SL, Ethier SP, Mevers EE, Clardy J, Roberts T, Chen C, Li Q, Wang L, Yang M, Zhao JJ, Wang Q. Oncotarget 9 23878-23889 (2018)
  64. PH domain-mediated autoinhibition and oncogenic activation of Akt. Bae H, Viennet T, Park E, Chu N, Salguero A, Eck MJ, Arthanari H, Cole PA. Elife 11 e80148 (2022)
  65. Productive induced metastability in allosteric modulation of kinase function. Montes de Oca J, Rodriguez Fris A, Appignanesi G, Fernández A. FEBS J. 281 3079-3091 (2014)
  66. Protein Kinase B (PKB/AKT) Protects IDH-Mutated Glioma from Ferroptosis via Nrf2. Liu Y, Chou FJ, Lang F, Zhang M, Song H, Zhang W, Davis DL, Briceno NJ, Zhang Y, Cimino PJ, Zaghloul KA, Gilbert MR, Armstrong TS, Yang C. Clin Cancer Res 29 1305-1316 (2023)
  67. Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole-1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides. Zahoor AF, Saeed S, Rasul A, Noreen R, Irfan A, Ahmad S, Faisal S, Al-Hussain SA, Saeed MA, Muhammed MT, Muhammad ZA, Zaki MEA. Biomedicines 11 3078 (2023)


Quick links