Citation: CHEN Zheng-Jun, JIANG Qing-Lin, HE Gu, HAN Bo, GUO Li. Multicomplex-Based Pharmacophore and QSAR of Aryl-Sulfamides as Pyruvate Kinase M2 Activators[J]. Acta Physico-Chimica Sinica, ;2013, 29(08): 1793-1803. doi: 10.3866/PKU.WHXB201305152 shu

Multicomplex-Based Pharmacophore and QSAR of Aryl-Sulfamides as Pyruvate Kinase M2 Activators

  • Received Date: 11 March 2013
    Available Online: 15 May 2013

    Fund Project: 国家自然科学基金(30901837, 81001357, 81273471)资助项目 (30901837, 81001357, 81273471)

  • Pyruvate kinase M2 (PKM2) is well-known as a potential target for cancer therapy. In this study, the multicomplex-based pharmacophore (MCBP)-guided method was used to generate a comprehensive pharmacophore of PKM2 kinase based on a collection of crystal structures of PKM2- activator complex. This model was successfully used to identify the bioactive conformation and align 62 structurally diverse aryl-sulfamide derivatives. Quantitative structure-activity relationship (QSAR) analyses were performed on these PKM2 activators based on MCBP-guided alignment. With the comparative molecular field analysis (CoMFA) model, the cross-validated value (q2) was 0.545, and the non-crossvalidated value (r2) was 0.966. With the comparative molecular similarity indices analysis (CoMSIA) model, q2 and r2 were 0.653 and 0.987. These results may provide important information for further design of novel PKM2 activators.

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    1. [1]

      (1) Tennant, D. A.; Duran, R. V.; ttlieb, E. Nature Rev. Cancer2010, 10, 267. doi: 10.1038/nrc2817

    2. [2]

      (2) Vander Heiden, M. G. Nature Rev. Drug Discov. 2011, 10, 671.doi: 10.1038/nrd3504

    3. [3]

      (3) Cairns, R. A.; Harris, I. S.; Mak, T.W. Nature Rev. Cancer 2011,11, 85.

    4. [4]

      (4) Levine, A. J.; Puzio-Kuter, A. M. Science 2010, 330, 1340.doi: 10.1126/science.1193494

    5. [5]

      (5) Warburg, O. Science 1956, 123, 309. doi: 10.1126/science.123.3191.309

    6. [6]

      (6) Vander Heiden, M. G.; Cantley, L. C.; Thompson, C. B. Science2009, 324, 1029. doi: 10.1126/science.1160809

    7. [7]

      (7) Dang, C. V.; Kim, J.W.; Gao, P.; Yustein, J. Nat. Rev. Cancer2008, 8, 51. doi: 10.1038/nrc2274

    8. [8]

      (8) Robey, R. B.; Hay, N. Semin. Cancer Biol. 2009, 19, 25.doi: 10.1016/j.semcancer.2008.11.010

    9. [9]

      (9) Shaw, R. J. Curr. Opin. Cell Biol. 2006, 18, 598. doi: 10.1016/j.ceb.2006.10.005

    10. [10]

      (10) Diaz-Ruiz, R.; Ri ulet, M.; Devin, A. Biochimica et Biophysica Acta-Bioenergetics 2011, 1807, 568. doi: 10.1016/j.bbabio.2010.08.010

    11. [11]

      (11) Dombrauckas, J. D.; Santarsiero, B. D.; Mesecar, A. D.Biochemistry 2005, 44, 9417. doi: 10.1021/bi0474923

    12. [12]

      (12) Takenaka, M.; Yamada, K.; Lu, T.; Kang, R.; Tanaka, T.;Noguchi, T. Eur. J. Biochem. 1996, 235, 366. doi: 10.1111/ejb.1996.235.issue-1-2

    13. [13]

      (13) Christofk, H. R.; Vander Heiden, M. G.; Harris, M. H.;Ramanathan, A.; Gerszten, R. E.;Wei, R.; Fleming, M. D.;Schreiber, S. L.; Cantley, L. C. Nature 2008, 452, 230.doi: 10.1038/nature06734

    14. [14]

      (14) Mao, J. Z.; Guo,W. H.; Shi, H. S.; Zhao, Y.W.; Yang, H. S.Journal of Sichuan University (Medical Science Edition) 2011,42, 308. [毛婧芝, 郭文浩, 石华山, 赵玉伟, 杨寒朔. 四川大学学报(医学版), 2011, 42, 308.]

    15. [15]

      (15) Boxer, M. B.; Jiang, J. K.; Vander Heiden, M. G.; Shen, M.;Skoumbourdis, A. P.; Southall, N.; Veith, H.; Leister,W.;Austin, C. P.; Park, H.W.; Inglese, J.; Cantley, L. C.; Auld, D.S.; Thomas, C. J. J. Med. Chem. 2010, 53, 1048. doi: 10.1021/jm901577g

    16. [16]

      (16) Thomas, C. J.; Boxer, M. B.; Jiang, J. K.; Vander Heiden, M. G.;Walsh, M. J.; Brimacombe, K.; Shen, M.; Skoumbourdis, A. P.;Park, H.W.; Cantley, L. C.; Auld, D. S. Abstr. Pap. Am. Chem. Soc. 2011, 242, 233-MEDI.

    17. [17]

      (17) Anastasiou, D.; Poulogiannis, G.; Asara, J. M.; Boxer, M. B.;Jiang, J. K.; Shen, M.; Bellinger, G.; Sasaki, A. T.; Locasale, J.W.; Auld, D. S.; Thomas, C. J.; Vander Heiden, M. G.; Cantley,L. C. Science 2011, 334, 1278. doi: 10.1126/science.1211485

    18. [18]

      (18) Anastasiou, D.; Yu, Y. M.; Israelsen,W. J.; Jiang, J. K.; Boxer,M. B.; Hong, B. S.; Tempel,W.; Dimov, S.; Shen, M.; Jha, A.;Yang, H.; Mattaini, K. R.; Metallo, C. M.; Fiske, B. P.; Courtney,K. D.; Malstrom, S.; Khan, T. M.; Kung, C.; Skoumbourdis, A.P.; Veith, H.; Southall, N.;Walsh, M. J.; Brimacombe, K. R.;Leister,W.; Lunt, S. Y.; Johnson, Z. R.; Yen, K. E.; Kunii, K.;Davidson, S. M.; Christofk, H. R.; Austin, C. P.; Inglese, J.;Harris, M. H.; Asara, J. M.; Stephanopoulos, G.; Salituro, F. G.;Jin, S. F.; Dang, L.; Auld, D. S.; Park, H.W.; Cantley, L. C.;Thomas, C. J.; Heiden, M. G. V. Nat. Chem. Biol. 2012, 8, 839.doi: 10.1038/nchembio.1060

    19. [19]

      (19) Anastasiou, D.; Yu, Y. M.; Israelsen,W. J.; Jiang, J. K.; Boxer,M. B.; Hong, B. S.; Tempel,W.; Dimov, S.; Shen, M.; Jha, A.;Yang, H.; Mattaini, K. R.; Metallo, C. M.; Fiske, B. P.; Courtney,K. D.; Malstrom, S.; Khan, T. M.; Kung, C.; Skoumbourdis, A.P.; Veith, H.; Southall, N.;Walsh, M. J.; Brimacombe, K. R.;Leister,W.; Lunt, S.Y.; Johnson, Z. R.;Yen, K. E.; Kunii, K.;Davidson, S. M.; Christofk, H. R.; Austin, C. P.; Inglese, J.;Harris, M. H.; Asara, J. M.; Stephanopoulos, G.; Salituro, F. G.;Jin, S. F.; Dang, L. N.; Auld, D. S.; Park, H.W.; Cantley, L. C.;Thomas, C. J.; Vander Heiden, M. G. Nat. Chem. Biol. 2012, 8,1008.

    20. [20]

      (20) Jiang, J. K.; Boxer, M. B.; Vander Heiden, M. G.; Shen, M.;Skoumbourdis, A. P.; Southall, N.; Veith, H.; Leister,W.;Austin, C. P.; Park, H.W.; Inglese, J.; Cantley, L. C.; Auld, D.S.; Thomas, C. J. Bioorganic & Medicinal Chemistry Letters2010, 20, 3387. doi: 10.1016/j.bmcl.2010.04.015

    21. [21]

      (21) Walsh, M. J.; Brimacombe, K. R.; Veith, H.; Bougie, J. M.;Daniel, T.; Leister,W.; Cantley, L. C.; Israelsen,W. J.; VanderHeiden, M. G.; Shen, M.; Auld, D. S.; Thomas, C. J.; Boxer, M.B. Bioorganic & Medicinal Chemistry Letters 2011, 21, 6322.doi: 10.1016/j.bmcl.2011.08.114

    22. [22]

      (22) Kubinyi, H. Drug Discov. Today 1997, 11, 457.

    23. [23]

      (23) Kubinyi, H. Drug Discov. Today 1997, 12, 538.

    24. [24]

      (24) SYBYL Molecular Modeling Software; Tripos Inc.: St. Louis,MO, USA, 2012.

    25. [25]

      (25) http://www.rcsb.org

    26. [26]

      (26) Discovery Studio, version 3.5; Accelrys Inc.: San Die , CA,USA, 2012.

    27. [27]

      (27) Kang, C. M.; Zhao, X. H.;Wang, X. Y.; Cheng, J. G.; Lü, Y. T.Acta Phys. -Chim. Sin. 2013, 29, 431. [康从民, 赵绪浩, 王新宇, 程家高, 吕英涛. 物理化学学报, 2013, 29, 431.]doi: 10.3866/PKU.WHXB201211151

    28. [28]

      (28) McIntosh, A. R.; Bookstein, F. L.; Haxby, J. V.; Grady, C. L.Neuroimage 1996, 3, 143. doi: 10.1006/nimg.1996.0016

    29. [29]

      (29) Cramer, R. D. Perspect Drug Discov. Des. 1993, 1, 269.doi: 10.1007/BF02174528

    30. [30]

      (30) Qiao, K.; Zeng, L. X.; Jin, H.W.; Liu, Z. M.; Zhang, L. R. Acta Phys. -Chim. Sin. 2012, 28, 1509. [乔康, 曾凌晓, 金宏威,刘振明, 张亮仁. 物理化学学报, 2012, 28, 1509.] doi: 10.3866/PKU.WHXB201203272

    31. [31]

      (31) Tropsha, A.; lbraikh, A. J. Mol. Graph. Model. 2002, 20, 269.doi: 10.1016/S1093-3263(01)00123-1

    32. [32]

      (32) Chaudhaery, S. S.; Roy, K. K.; Saxena, A. K. J. Chem Inf. Model. 2009, 49, 1590. doi: 10.1021/ci900049e

    33. [33]

      (33) Ouyang, L.; He, G.; Huang,W.; Song, X. R.;Wu, F. B.; Xiang,M. L. Int. J. Mol. Sci. 2012, 13, 5348. doi: 10.3390/ijms13055348

    34. [34]

      (34) He, G.; Qiu, M. H.; Li, R.; Ouyang, L.;Wu, F. B.; Song, X. R.;Cheng, L.; Xiang, M. L.; Yu, L. T. Chem. Biol. Drug Des. 2012,79, 960. doi: 10.1111/jpp.2012.79.issue-6

    35. [35]

      (35) He, G.; Qiu, M. H.; Li, R.; Song, X. R.; Zheng, X.; Shi, J. Y.;Xu, G. B.; Han, J.; Yu, L. T.; Yang, S. Y.; Chen, L. J.;Wei, Y. Q.Molecular Simulation 2011, 37, 31. doi: 10.1080/08927022.2010.517529

    36. [36]

      (36) Wu, F. B.; Xu, T.; He, G.; Ouyang, L.; Han, B.; Peng, C.; Song,X. R.; Xiang, M. L. Int. J. Mol. Sci. 2012, 13, 15668.doi: 10.3390/ijms131215668

    37. [37]

      (37) Clark, M.; Cramer, R. D.; Jones, D. M.; Patterson, D. E.;Simeroth, P. E. Tetrahedron Comput. Method 1990, 3, 47.doi: 10.1016/0898-5529(90)90120-W

    38. [38]

      (38) Dai, Z. J.; Zhou,W.; Yuan, Z. M. Acta Phys.-Chim. Sin. 2011,27, 1654. [代志军, 周玮, 袁哲明. 物理化学学报, 2011, 27,1654.] doi: 10.3866/PKU.WHXB20110735


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