Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 873010, 12 pages
http://dx.doi.org/10.1155/2014/873010
Research Article

Potential Smoothened Inhibitor from Traditional Chinese Medicine against the Disease of Diabetes, Obesity, and Cancer

1School of Pharmacy, China Medical University, Taichung 40402, Taiwan
2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
3Department of Acupuncture, China Medical University Hospital, Taichung, Taiwan
4Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, Taiwan
5Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan
6School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan
7Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

Received 14 February 2014; Accepted 15 February 2014; Published 1 July 2014

Academic Editor: Chung Y. Hsu

Copyright © 2014 Kuan-Chung Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Jauch-Chara and K. M. Oltmanns, “Obesity—a neuropsychological disease? Systematic review and neuropsychological model,” Progress in Neurobiology, vol. 114, pp. 84–101, 2014. View at Publisher · View at Google Scholar
  2. A. J. Guri, R. Hontecillas, and J. Bassaganya-Riera, “Peroxisome proliferator-activated receptors: bridging metabolic syndrome with molecular nutrition,” Clinical Nutrition, vol. 25, no. 6, pp. 871–885, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. R. Teperino, S. Amann, M. Bayer et al., “Hedgehog partial agonism drives warburg-like metabolism in muscle and brown fat,” Cell, vol. 151, no. 2, pp. 414–426, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. Jiang, X. Li, W. Yang et al., “PKM2 regulates chromosome segregation and mitosis progression of tumor cells,” Molecular Cell, vol. 53, no. 1, pp. 75–87, 2014. View at Publisher · View at Google Scholar
  5. Y.-M. Chang, B. K. Velmurugan, W.-W. Kuo et al., “Inhibitory effect of alpinate Oxyphyllae fructus extracts on Ang II-induced cardiac pathological remodeling-related pathways in H9c2 cardiomyoblast cells,” BioMedicine, vol. 3, no. 4, pp. 148–152, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. M. Leung, K. L. Wong, S. W. Chen et al., “Down-regulation of voltage-gated Ca2+ channels in Ca2+ store-depleted rat insulinoma RINm5F cells,” BioMedicine, vol. 3, no. 3, pp. 130–139, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. M. A. Leissring, E. Malito, S. Hedouin et al., “Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin,” PLoS ONE, vol. 5, no. 5, Article ID e10504, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. C.-L. Jao, S.-L. Huang, and K.-C. Hsu, “Angiotensin I-converting enzyme inhibitory peptides: inhibition mode, bioavailability, and antihypertensive effects,” BioMedicine, vol. 2, no. 4, pp. 130–136, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. A. P. McMahon, P. W. Ingham, and C. J. Tabin, “Developmental roles and clinical significance of Hedgehog signaling,” Current Topics in Developmental Biology, vol. 53, pp. 1–114, 2003. View at Google Scholar · View at Scopus
  10. S. J. Scales and F. J. de Sauvage, “Mechanisms of Hedgehog pathway activation in cancer and implications for therapy,” Trends in Pharmacological Sciences, vol. 30, no. 6, pp. 303–312, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Sekulic, A. R. Mangold, D. W. Northfelt, and P. M. Lorusso, “Advanced basal cell carcinoma of the skin: targeting the Hedgehog pathway,” Current Opinion in Oncology, vol. 25, no. 3, pp. 218–223, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. R. McMillan and W. Matsui, “Molecular pathways: the hedgehog signaling pathway in cancer,” Clinical Cancer Research, vol. 18, no. 18, pp. 4883–4888, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. V. Chenna, C. Hu, and S. R. Khan, “Synthesis and cytotoxicity studies of Hedgehog enzyme inhibitors SANT-1 and GANT-61 as anticancer agents,” Journal of Environmental Science and Health A: Toxic/Hazardous Substances and Environmental Engineering, vol. 49, no. 6, pp. 641–647, 2014. View at Publisher · View at Google Scholar
  14. D. Amakye, Z. Jagani, and M. Dorsch, “Unraveling the therapeutic potential of the Hedgehog pathway in cancer,” Nature Medicine, vol. 19, no. 11, pp. 1410–1422, 2013. View at Publisher · View at Google Scholar
  15. D. D. Von Hoff, P. M. LoRusso, C. M. Rudin et al., “Inhibition of the hedgehog pathway in advanced basal-cell carcinoma,” The New England Journal of Medicine, vol. 361, no. 12, pp. 1164–1172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. A. E. Proctor, L. A. Thompson, and C. L. O'Bryant, “Vismodegib: an inhibitor of the hedgehog signaling pathway in the treatment of basal cell carcinoma,” The Annals of Pharmacotherapy, vol. 48, no. 1, pp. 99–106, 2014. View at Publisher · View at Google Scholar
  17. M. Xin, L. Zhang, F. Tang et al., “Design, synthesis, and evaluation of pyrrolo[2,1-f][1,2,4]triazine derivatives as novel hedgehog signaling pathway inhibitors,” Bioorganic & Medicinal Chemistry, vol. 22, no. 4, pp. 1429–1440, 2014. View at Publisher · View at Google Scholar
  18. R. Kunstfeld, “Smoothened inhibitors in the treatment of advanced basal cell carcinomas,” Current Opinion in Oncology, vol. 26, no. 2, pp. 184–195, 2014. View at Publisher · View at Google Scholar
  19. C. Y. Chen, “A novel integrated framework and improved methodology of computer-aided drug design,” Current Topics in Medicinal Chemistry, vol. 13, no. 9, pp. 965–988, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Y. Chen and C. Y. C. Chen, “Insights into designing the dual-targeted HER2/HSP90 inhibitors,” Journal of Molecular Graphics and Modelling, vol. 29, no. 1, pp. 21–31, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. S. C. Yang, S. S. Chang, H. Y. Chen, and C. Y. C. Chen, “Identification of potent EGFR inhibitors from TCM Database@Taiwan,” PLoS Computational Biology, vol. 7, no. 10, Article ID e1002189, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. A. Tsou, K. C. Chen, H. C. Lin, S. S. Chang, and C. Y. C. Chen, “Uroporphyrinogen decarboxylase as a potential target for specific components of Traditional Chinese Medicine: a virtual screening and molecular dynamics study,” PLoS ONE, vol. 7, no. 11, Article ID e50087, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. A. Tsou, K. C. Chen, S. S. Chang, Y. R. Wen, and C. Y. Chen, “A possible strategy against head and neck cancer: in silico investigation of three-in-one inhibitors,” Journal of Biomolecular Structure and Dynamics, vol. 31, no. 12, pp. 1358–1369, 2013. View at Publisher · View at Google Scholar
  24. K. C. Chen, S. S. Chang, F. J. Tsai, and C. Y. Chen, “Han ethnicity-specific type 2 diabetic treatment from Traditional Chinese Medicine?” Journal of Biomolecular Structure and Dynamics, vol. 31, no. 11, pp. 1219–1235, 2013. View at Publisher · View at Google Scholar
  25. K. C. Chen, M. F. Sun, S. C. Yang et al., “Investigation into potent inflammation inhibitors from Traditional Chinese Medicine,” Chemical Biology and Drug Design, vol. 78, no. 4, pp. 679–688, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. S. S. Chang, H. J. Huang, and C. Y. Chen, “Two birds with one stone? Possible dual-targeting H1N1 inhibitors from Traditional Chinese Medicine,” PLoS Computational Biology, vol. 7, no. 12, Article ID e1002315, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. H. J. Huang, K. J. Lee, H. W. Yu, H. Chen, F. Tsai, and C. Y. Chen, “A novel strategy for designing the selective PPAR agonist by the “sum of activity” model,” Journal of Biomolecular Structure and Dynamics, vol. 28, no. 2, pp. 187–200, 2010. View at Google Scholar · View at Scopus
  28. K. C. Chen, S. S. Chang, H. J. Huang, T. Lin, Y. Wu, and C. Y. Chen, “Three-in-one agonists for PPAR-α, PPAR-γ, and PPAR-δ from Traditional Chinese Medicine,” Journal of Biomolecular Structure and Dynamics, vol. 30, no. 6, pp. 662–683, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. K.-C. Chen and C. Y. C. Chen, “Stroke prevention by Traditional Chinese Medicine? A genetic algorithm, support vector machine and molecular dynamics approach,” Soft Matter, vol. 7, no. 8, pp. 4001–4008, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. K. C. Chen, K. W. Chang, H. Y. Chen, and C. Y. C. Chen, “Traditional Chinese Medicine, a solution for reducing dual stroke risk factors at once?” Molecular BioSystems, vol. 7, no. 9, pp. 2711–2719, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. T. T. Chang, K. C. Chen, K. W. Chang et al., “In silico pharmacology suggests ginger extracts may reduce stroke risks,” Molecular BioSystems, vol. 7, no. 9, pp. 2702–2710, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. W. Ieongtou, S. S. Chang, D. Wu et al., “Molecular level activation insights from a NR2A/NR2B agonist,” Journal of Biomolecular Structure and Dynamics, vol. 32, no. 5, pp. 683–693, 2014. View at Publisher · View at Google Scholar
  33. H. J. Huang, Y. R. Jian, and C. Y. Chen, “Traditional Chinese Medicine application in HIV: an in silico study,” Journal of Biomolecular Structure and Dynamics, vol. 32, no. 1, pp. 1–12, 2014. View at Publisher · View at Google Scholar
  34. W. I. Tou, S. S. Chang, C. C. Lee, and C. Y. Chen, “Drug design for neuropathic pain regulation from Traditional Chinese Medicine,” Scientific Reports, vol. 3, p. 844, 2013. View at Google Scholar · View at Scopus
  35. K. C. Chen, Y. R. Jian, M. F. Sun, T. T. Chang, C. C. Lee, and C. Y. Chen, “Investigation of silent information regulator 1 (Sirt1) agonists from Traditional Chinese Medicine,” Journal of Biomolecular Structure and Dynamics, vol. 31, no. 11, pp. 1207–1218, 2013. View at Publisher · View at Google Scholar
  36. C. Y. C. Chen, “TCM Database@Taiwan: the world's largest Traditional Chinese Medicine database for drug screening in silico,” PLoS ONE, vol. 6, no. 1, Article ID e15939, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. W. I. Tou and C. Y. Chen, “May disordered protein cause serious drug side effect?” Drug Discovery Today, vol. 19, no. 4, pp. 367–372, 2014. View at Publisher · View at Google Scholar
  38. C. Y. C. Chen and W. I. Tou, “How to design a drug for the disordered proteins?” Drug Discovery Today, vol. 18, no. 19-20, pp. 910–915, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Wang, H. Wu, V. Katritch et al., “Structure of the human smoothened receptor bound to an antitumour agent,” Nature, vol. 497, no. 7449, pp. 338–343, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. B. Xue, R. L. Dunbrack, R. W. Williams, A. K. Dunker, and V. N. Uversky, “PONDR-FIT: a meta-predictor of intrinsically disordered amino acids,” Biochimica et Biophysica Acta—Proteins and Proteomics, vol. 1804, no. 4, pp. 996–1010, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. B. R. Brooks, R. E. Bruccoleri, B. D. Olafson, D. J. States, S. Swaminathan, and M. Karplus, “CHARMM: a program for macromolecular energy minimization and dynamics calculations,” Journal of Computational Chemistry, vol. 4, no. 2, pp. 187–217, 1983. View at Publisher · View at Google Scholar
  42. C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings,” Advanced Drug Delivery Reviews, vol. 46, no. 1–3, pp. 3–26, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. C. M. Venkatachalam, X. Jiang, T. Oldfield, and M. Waldman, “LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites,” Journal of Molecular Graphics and Modelling, vol. 21, no. 4, pp. 289–307, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. B. Hess, C. Kutzner, D. van der Spoel, and E. Lindahl, “GRGMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation,” Journal of Chemical Theory and Computation, vol. 4, no. 3, pp. 435–447, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. V. Zoete, M. A. Cuendet, A. Grosdidier, and O. Michielin, “SwissParam: a fast force field generation tool for small organic molecules,” Journal of Computational Chemistry, vol. 32, no. 11, pp. 2359–2368, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. R. Fletcher, Optimization, Academic Press, New York, NY, USA, 1969.