Pharmacophore modeling, virtual screening, and mo-lecular docking studies for discovery of novel Akt2 inhibitors

International Journal of Medical Sciences

Volumn 10, Issue 3, 2013, Pages 265-275

  Fei, Jia ^a   Zhou, Lu ^a   Liu, Tao ^a   Tang, Xiang Yang ^b  

^a SICHUAN UNIVERSITY   (China)

^b SOUTHEAST UNIVERSITY   (China)

Author keywords

Akt2; Docking; Inhibitor; Pharmacophore; Virtual screening

Indexed keywords

PROTEIN AKT2 INHIBITOR; PROTEIN KINASE B BETA; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG; ZINC 02110020; ZINC 08876929; ZINC 08877587; ZINC 12885936; ZINC 12890361; ZINC 13505894; ZINC 35288562;

ARTICLE; CHEMICAL DATABASE; CONTROLLED STUDY; DRUG DESIGN; DRUG DETERMINATION; DRUG MECHANISM; DRUG SCREENING; ENZYME INHIBITION; IC 50; MOLECULAR DOCKING; MOLECULAR MODEL; PHARMACOPHORE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; THREE DIMENSIONAL IMAGING; VIRTUAL REALITY;

AKT2; DOCKING; INHIBITOR; PHARMACOPHORE; VIRTUAL SCREENING.;

DATABASES, CHEMICAL; DRUG DISCOVERY; HUMANS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84873361992     PISSN: 14491907     EISSN: None     Source Type: Journal    
DOI: 10.7150/ijms.5344     Document Type: Article

References (18)

1. Siu T, Liang J, Arruda J, et al. Discovery of potent and cell-active allo-steric dual Akt 1 and 2 inhibitors. BIOORG MED CHEM LET. 2008; 18: 4186-4190.
2. Scheid MP, Woodgett JR. Unravelling the activation mechanisms of protein kinase B/Akt. FEBS LETT. 2003; 546: 108-112.
3. Cheng JQ, Lindsley CW, Cheng GZ, et al. The Akt/PKB pathway: mo-lecular target for cancer drug discovery. Oncogene. 2005; 24: 7482-7492.
4. Ko JH, Yeon W, Ryu S, et al. Synthesis and biological evaluation of 5-arylamino-6-chloro-1H-indazole-4,7-diones as inhibitors of protein kinase B/Akt. BIOORG MED CHEM LETT. 2006; 16: 6001-6005.
5. Xu R, Banka A, Blake JF, et al. Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA. BIOORG MED CHEM LETT. 2011; 21: 2335-2340.
6. Woods KW, Fischer JP, Claiborne A, et al. Synthesis and SAR of inda-zole-pyridine based protein kinase B/Akt inhibitors. BIOORGAN MED CHEM. 2006; 14: 6832-6846.
7. Li Q, Woods KW, Thomas S, et al. Synthesis and structure-activity rela-tionship of 3,4'-bispyridinylethylenes: Discovery of a potent 3-isoquinolinylpyriding inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer. BIOORG MED CHEM LETT. 2006; 16: 2000-2007.
8. Lippa B, Pan G, Corbett M, et al. Synthesis and structure based optimi-zation of novel Akt inhibitors. BIOORG MED CHEM LETT. 2008; 18: 3359-3363.
9. Thangapandian S, John S, Sakkiah S, et al. Potential virtual lead identi-fication in the discovery of renin inhibitors: Application of ligand and structure-based pharmacophore modeling approaches. EUR J MED CHEM. 2011; 46: 2469-2476.
10. Lindsley CW, Zhao Z, Leister WH, et al. Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. BIOORG MED CHEM LETT. 2005; 15: 761-764.
11. Zhao Z, Leister WH, Robinson RG, et al. Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors. BIOORG MED CHEM LETT. 2005; 15: 905-909.
12. Li Y, Liang J, Siu T, et al. Allosteric inhibitors of Akt1 and Akt2: Discov-ery of [1,2,4]triazolo[3,4-f][1,6]naphthyridines with potent and balanced activity. BIOORG MED CHEM LETT. 2009; 19: 834-836.
13. Hartnett JC, Barnett SF, Bilodeau MT, et al. Optimization of 2,3,5-trisubstituted pyridine derivatives as potent allosteric Akt1 and Akt2 inhibitors. BIOORG MED CHEM LETT. 2008; 18: 2194-2197.
14. Bilodeau MT, Balitza AE, Hoffman JM, et al. Allosteric inhibitors of Akt1 and Akt2: A naphthyridinone with efficacy in an A2780 tumor xenograft model. BIOORG MED CHEM LETT. 2008; 18:3178-3182.
15. Defeo-jones D, Barnett SF, Fu S, et al. Tumor cell sensitization to apop-totic stimuli by selective inhibition of specific Akt/PKB family members. MOL CANCER THER. 2005; 4: 271-279.
16. Ma X, Zhou L, Zuo ZL, et al. Molecular docking and 3-D QSAR studies of substituted 2,2-bisary-bicycloheptanes as human 5-lipoxygenase-Activating protein (FLAP) inhibitors. QSAR COMB SCI. 2008; 27: 1083-1091.
17. Chandrasekaran M, Sakkiah S, Lee KW. Combined ligand based phar-macophore modeling, virtual screening methods to identify critical chemical features of novel potential inhibitors for phosphodiesterase-5. J TAIWAN INST CHEM E. 2011; 42: 709-718.
18. Elumalai P, Liu HL, Zhao JH, et al. Pharmacophore modeling, virtual screening and docking studies to identify novel HNMT inhibitors. J TAIWAN INST CHEM. 2012; doi:10.1016/j.jtice.2012.01.004.