Virtual screening and biochemical evaluation of the inhibitors of dual-specificity phosphatase 26

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• 作者：Hwangseo Park (1)
  Ayoung Kyung (2) (3)
  Hyun-Ju Lee (2)
  Sunghyun Kang (2) (3)
  Tae-Sung Yoon (2) (3)
  Seong Eon Ryu (4)
  Dae Gwin Jeong (2) (3)
  
• 关键词：Virtual screening ; DUSP26 ; Inhibitor ; Docking ; Anticancer agents
• 刊名：Medicinal Chemistry Research
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：22
• 期：8
• 页码：3905-3910
• 全文大小：395KB
• 参考文献：1. Alkorta I, Blanco F, Solimannejad M, Elguero J (2008) Competition of hydrogen bonds and halogen bonds in complexes of hypohalous acids with nitrogenated bases. J Phys Chem A 112:10856-0863
  2. Ducruet AP, Vogt A, Wipf P, Lazo JS (2005) Dual specificity protein phosphatases: therapeutic targets for cancer and Alzheimer’s disease. Annu Rev Pharmacol Toxicol 45:725-50
  3. Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity a rapid access to atomic charges. Tetrahedron 36:3219-228
  4. Jeffrey GA (1997) An Introduction to hydrogen bonding. Oxford University Press, Oxford
  5. Kang H, Choi H, Park H (2007) Prediction of molecular solvation free energy based on the optimization of atomic solvation parameters with genetic algorithm. J Chem Info Model 47:509-14
  6. Lazo JS, Wipf P (2009) Phosphatases as targets for cancer treatment. Curr Opin Invest Drugs 10:1297-304
  7. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3-5
  8. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639-662
  9. Park H, Jeon JH (2007) Cubic equation governing the outer-region dielectric constant of globular proteins. Phys Rev E 75:021916
  10. Park H, Lee J, Lee S (2006) Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins 65:549-54
  11. Patterson KI, Brummer T, O’Brien PM, Daly RJ (2009) Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J 418:475-89
  12. Shang X, Vasudevan SA, Yu Y, Ge N, Ludwig AD, Wesson CL, Wang K, Burlingame SM, Zhao YJ, Rao PH, Lu X, Russell HV, Okcu MF, Hicks MJ, Shohet JM, Donehower LA, Nuchtern JG, Yang J (2010) Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma. Oncogene 29:4938-946
  13. Shoichet BK, Leach AR, Kuntz ID (1999) Ligand solvation in molecular docking. Proteins 34:4-6
  14. Song M, Park JE, Park SG, Lee DH, Choi HK, Park BC, Ryu SE, Kim JH, Cho S (2009) NSC-87877, inhibitor of SHP-1/2 PTPs, inhibits dual-specificity phosphatase 26 (DUSP26). Biochem Biophys Res Commun 381:491-95
  15. Stouten PFW, Fr?mmel C, Nakamura H, Sander C (1993) An effective solvation term based on atomic occupancies for use in protein simulations. Mol Simul 10:97-20
  16. Tanuma N, Nomura M, Ikeda M, Kasugai I, Tsubaki Y, Takagaki K, Kawamura T, Yamashita Y, Sato I, Sato M, Katakura R, Kikuchi K, Shima H (2009) Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion. Oncogene 28:752-61
  17. Vasudevan SA, Skoko J, Wang K, Burlingame SM, Patel PN, Lazo JS, Nuchtern JG, Yang J (2005) MKP-8, a novel MAPK phosphatase that inhibits p38 kinase. Biochem Biophys Res Commun 330:511-18
  18. Yu W, Imoto I, Inoue J, Onda M, Emi M, Inazawa J (2007) A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity. Oncogene 26:1178-187
  
• 作者单位：Hwangseo Park (1)
  Ayoung Kyung (2) (3)
  Hyun-Ju Lee (2)
  Sunghyun Kang (2) (3)
  Tae-Sung Yoon (2) (3)
  Seong Eon Ryu (4)
  Dae Gwin Jeong (2) (3)
  
  1. Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul, 143-747, Korea
  2. Medical Proteomics Research Center, Research Institute of Bioscience and Biotechnology, Daejeon, Korea
  3. Research Institute of Bioscience and Biotechnology, University of Science & Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, Korea
  4. Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Korea
  

文摘

Dual-specificity phosphatase 26 (DUSP26) has recently proved to be a promising therapeutical target for the treatment of human cancers. Here, we report the first example for a successful application of the structure-based virtual screening approach to identify nine novel inhibitors of DUSP26. These inhibitors are also screened for having desirable physicochemical properties as drug candidates and reveal a high potency with IC50 values ranging from 8 to 42?μM. Therefore, they deserve consideration for further development by structure–activity relationship (SAR) studies to optimize the anticancer activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of DUSP26 are addressed in detail.