Computational insights into the inhibitory mechanism of human AKT1 by an orally active inhibitor, MK-2206

PLoS ONE

Volumn 9, Issue 10, 2014, Pages

  Rehan, Mohd ^a   Beg, Mohd A ^a   Parveen, Shadma ^b   Damanhouri, Ghazi A ^a   Zaher, Galila F ^c  

^a KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

^b BAREILLY COLLEGE   (India)

^c Aziz University   (Saudi Arabia)

Author keywords

[No Author keywords available]

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; AMINO ACID; ISOPROTEIN; LIGAND; SOLVENT; AKT1 PROTEIN, HUMAN; ANTINEOPLASTIC AGENT; FUSED HETEROCYCLIC RINGS; PROTEIN BINDING; PROTEIN KINASE B;

AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DISSOCIATION CONSTANT; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR INTERACTION; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PROTEIN INTERACTION; SEQUENCE ALIGNMENT; CHEMISTRY; METABOLISM; MOLECULAR GENETICS;

AMINO ACID SEQUENCE; ANTINEOPLASTIC AGENTS; BINDING SITES; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; MOLECULAR DOCKING SIMULATION; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 84908120086     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0109705     Document Type: Article

References (42)

1. Martelli AM, Evangelisti C, Chappell W, Abrams SL, Basecke J, et al. (2011) Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway. Leukemia 25: 1064-1079.
2. Liu P, Cheng H, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8: 627-644.
3. Kannan N, Haste N, Taylor SS, Neuwald AF (2007) The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Proc Natl Acad Sci USA 104: 1272-1277.
4. Yang J, Cron P, Thompson V, Good VM, Hess D, et al. (2002) Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Mol Cell 9: 1227-1240.
5. Brazil DP, Yang ZZ, Hemmings BA (2004) Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci 29: 233-242.
6. Carnero A (2010) The PKB/AKT pathway in cancer. Curr Pharm Des 16: 34-44.
7. Winograd-Katz SE, Levitzki A (2006) Cisplatin induces PKB/Akt activation and p38 (MAPK) phosphorylation of the EGF receptor. Oncogene 25: 7381-7390.
8. Rao E, Jiang C, Ji M, Huang X, Iqbal J, et al. (2012) The miRNA-17∼92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation. Leukemia 26: 1064-1072.
9. Wang P, Zhang L, Hao Q, Zhao G (2011) Developments in selective small molecule ATP-targeting the serine/threonine kinase Akt/PKB. Mini Rev Med Chem 11: 1093-1107.
10. Polak R, Buitenhuis M (2012) The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia. Blood 119: 911-923.
11. Barnett SF, Defeo-Jones D, Fu S, Hancock PJ, Haskell KM, et al. (2005) Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J 385: 399-408.
12. Lindsley CW, Zhao Z, Leister WH, Robinson RG, Barnett SF, et al. (2005) Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett 15: 761-764.
13. Wu W-I, Voegtli WC, Sturgis HL, Dizon FP, Vigers GPA, et al. (2010) Crystal Structure of Human AKT1 with an Allosteric Inhibitor Reveals a New Mode of Kinase Inhibition. PLoS ONE 5: e12913.
14. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, et al. (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 9: 1956-1967.
15. Cheng Y, Zhang Y, Zhang L, Ren X, Huber-Keener KJ, et al. (2011) MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis. Mol Cancer Ther 11: 154-164.
16. Tan S, Ng Y, James DE (2011) Next-generation Akt inhibitors provide greater specificity: effects on glucose metabolism in adipocytes. Biochem J 435: 539-544.
17. Yan L (2009) MK-2206: a potent oral allosteric AKT inhibitor. Proceedings of the 100th Annual Meeting of the American Association for Cancer Research (April 18-22, 2009, Denver, CO). Abstract Number: DDT01-1.
18. Simioni C, Neri LM, Tabellini G, Ricci F, Bressanin D, et al. (2012) Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia. Leukemia 26: 2336-2342.
19. Pant A, Irene IL, Lu Z, Rueda BR, Schink J, Kim JJ (2012) Inhibition of AKT with the Orally Active Allosteric AKT Inhibitor, MK-2206, Sensitizes Endometrial Cancer Cells to Progestin. PLoS ONE 7: e41593.
20. Knowles JA, Golden B, Yan L, Carroll WR, Helman EE, et al. (2011) Disruption of the AKT pathway inhibits metastasis in an orthotopic model of head and neck squamous cell carcinoma. The Laryngoscope 121: 2359-2365.
21. Liu R, Liu D, Trink E, Bojdani E, Ning G, et al. (2011) The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway. J Clin Endocrinol and metab 96: E577-585.
22. Pal SK, Reckamp K, Yu H, Figlin RA (2010) Akt inhibitors in clinical development for the treatment of cancer. Expert Opin Investig Drugs 19: 1355-1366.
23. Tolcher AW, Yap TA, Fearen I, Taylor A, Carpenter C, et al. (2009) A phase I study of MK-2206, an oral potent allosteric Akt inhibitor (Akti), in patients (pts) with advanced solid tumor (ST). J Clin Oncol 27: 3503.
24. Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, et al. (2011) First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors. J Clin Oncol 29: 4688-4695.
25. Chen S-F, Cao Y, Han S, Chen J-Z (2014) Insight into the structural mechanism for PKBα allosteric inhibitionby molecular dynamics simulations and free energy calculations. J Mol Graph Model 48: 36-46.
26. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234: 779-815.
27. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK - a program to check the stereochemical quality of protein structures. J Appl Cryst 26: 283-291.
28. Ewing TJ, Makino S, Skillman AG, Kuntz ID (2001) DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases. J Comput Aided Mol Des 15: 411-428.
29. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
30. DeLano WL (2002) The PyMOL Molecular Graphics System. San Carlos, CA. DeLano Scientific.
31. Laskowski RA, Swindells MB (2011) LigPlot+ : multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51: 2778-2786.
32. Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8: 127-134.
33. Ghosh KS, Sen S, Sahoo BK, Dasgupta S (2009) A spectroscopic investigation into the interactions of 3′-O-carboxy esters of thymidine with bovine serum albumin. Biopolymers 91: 737-744.
34. Hubbard SJ, Thornton JM (1993) 'Naccess', computer program. Technical Report. Department of Biochemistry and Molecular Biology, University College London.
35. Wang R, Lai L, Wang S (2002) Further development and validation of empirical scoring functions for structure-based binding affinity prediction. J Comput Aided Mol Des 16: 11-26.
36. Wang R, Lai L, Wang S (2003) Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem 46: 2287-2303.
37. Devaurs D, Bouard L, Vaisset M, Zanon C, Al-Bluwi I, et al. (2013) MoMALigPath: a web server to simulate protein-ligand unbinding. Nucleic Acids Res, 41(W1): W297-302.
38. Cortés J, Siméon T, Ruiz de Angulo V, Guieysse D, et al. (2005) A path planning approach for computing large-amplitude motions of flexible molecules. Bioinformatics 21(Suppl.1): i116-i125.
39. Robert CE (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32 (5): 1792-1797.
40. Clamp M, Cuff J, Searle SM, Barton GJ (2004) The Jalview Java alignment editor. Bioinformatics 20: 426-427.
41. Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ (2009) Jalview Version 2 - a multiple sequence alignment editor and analysis workbench. Bioinformatics 25 (9): 1189-1191.
42. Green CJ, Göransson O, Kular GS, Leslie NR, Gray A, et al. (2008) Use of Akt inhibitor and a drug-resistant mutant validates a critical role for protein kinase B/Akt in the insulin-dependent regulation of glucose and system A amino acid uptake. J Biol Chem 283: 27653-27667.