Recent progress in the identification of adenosine monophosphate-activated protein kinase (AMPK) activators

Bioorganic and Medicinal Chemistry Letters

Volumn 26, Issue 21, 2016, Pages 5139-5148

  Cameron, Kimberly O ^a   Kurumbail, Ravi G ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Allostery; AMPK; CBM; CBS; Crystallography; Enzyme activators

Indexed keywords

ENZYME ACTIVATOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE;

ANIMAL; CHEMISTRY; ENZYME ACTIVATION; HUMAN; METABOLISM; PHOSPHORYLATION; PROTEIN CONFORMATION;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ENZYME ACTIVATION; ENZYME ACTIVATORS; HUMANS; PHOSPHORYLATION; PROTEIN CONFORMATION;

EID: 84992416929     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2016.09.065     Document Type: Review

References (110)

1. 1 Steinberg, G.R., Kemp, B.E., Physiol. Rev., 89, 2009, 1025.
2. 2 Hardie, D.G., Curr. Opin. Cell Biol., 33, 2015, 1.
3. 3 Oakhill, J.S., Scott, J.W., Kemp, B.E., Trends Endocrinol. Metab., 23, 2012, 125.
4. 4 Weikel, K.A., Ruderman, N.B., Cacicedo, J.M., Metabolism, 65, 2016, 634.
5. 5 Mounier, R., Théret, M., Lantier, L., Foretz, M., Viollet, B., Trends Endocrinol. Metab., 26, 2015, 275.
6. 6 Pelosse, M., Tokarska-Schlattner, M., Schlattner, U., AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart, 2015, Springer, Switzerland, 187.
7. 7 Alers, S., Loffler, A.S., Wesselborg, S., Stork, B., Mol. Cell. Biol., 32, 2012, 2.
8. 8 Kim, J., Shin, J., Ha, J., Expert Opin. Ther. Pat., 25, 2015, 261.
9. 9 Zaks, I., Getter, T., Gruzman, A., Future Med. Chem., 6, 2014, 1325.
10. 10 Miglianico, M., Nicolaes, G.A.F., Neumann, D., J. Med. Chem., 59, 2016, 2879.
11. 11 Calabrese, M.F., Rajamohan, F., Harris, M.S., Caspers, N.L., Magyar, R., Withka, J.M., Wang, H., Borzilleri, K.A., Sahasrabudhe, P.V., Hoth, L.R., Geoghegan, K.F., Han, S., Brown, J., Subashi, T.A., Reyes, A.R., Frisbie, R.K., Ward, J., Miller, R.A., Landro, J.A., Londregan, A.T., Carpino, P.A., Cabral, S., Smith, A.C., Conn, E.L., Cameron, K.O., Qiu, X., Kurumbail, R.G., Structure, 22, 2014, 1161.
12. 12 Chen, L., Xin, F.J., Wang, J., Hu, J., Zhang, Y.Y., Wan, S., Cao, L.S., Lu, C., Li, P., Yan, S.F., Neumann, D., Schlattner, U., Xia, B., Wang, Z.X., Wu, J.W., Nature, 498, 2013, E8.
13. 13 Li, X., Wang, L., Zhou, X.E., Ke, J., de Waal, P.W., Gu, X., Tan, M.H., Wang, D., Wu, D., Xu, H.E., Melcher, K., Cell Res., 25, 2015, 50.
14. 14 Xiao, B., Sanders, M.J., Carmena, D., Bright, N.J., Haire, L.F., Underwood, E., Patel, B.R., Heath, R.B., Walker, P.A., Hallen, S., Giordanetto, F., Martin, S.R., Carling, D., Gamblin, S.J., Nat. Commun., 4, 2013, 2017.
15. 15 Chen, L., Wang, J., Zhang, Y.Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.X., Wu, J.W., Nat. Struct. Mol. Biol., 19, 2012, 716.
16. 16 Xiao, B., Heath, R., Saiu, P., Leiper, F.C., Leone, P., Jing, C., Walker, P.A., Haire, L., Eccleston, J.F., Davis, C.T., Martin, S.R., Carling, D., Gamblin, S.J., Nature, 449, 2007, 496.
17. 17 Xiao, B., Sanders, M.J., Underwood, E., Heath, R., Mayer, F.V., Carmena, D., Jing, C., Walker, P.A., Eccleston, J.F., Haire, L.F., Saiu, P., Howell, S.A., Aasland, R., Martin, S.R., Carling, D., Gamblin, S.J., Nature, 472, 2011, 230.
18. 18 Gowans, G.J., Hawley, S.A., Ross, F.A., Hardie, D.G., Cell Metab., 18, 2013, 556.
19. 19 Oakhill, J.S., Steel, R., Chen, Z.-P., Scott, J.W., Ling, N., Tam, S., Kemp, B.E., Science, 332, 2011, 1433.
20. 20 Rajamohan, F., Reyes, A.R., Frisbie, R.K., Hoth, L.R., Sahasrabudhe, P., Magyar, R., Landro, J.A., Withka, J.M., Caspers, N.L., Calabrese, M.F., Ward, J., Kurumbail, R.G., Biochem. J., 473, 2016, 581.
21. 21 Friedrichsen, M., Mortensen, B., Pehmøller, C., Birk, J.B., Wojtaszewski, J.F., Mol. Cell. Endocrinol., 366, 2013, 204.
22. 22 Hunter, R.W., Treebak, J.T., Wojtaszewski, J.F., Sakamoto, K., Diabetes, 60, 2011, 766.
23. 23 Treebak, J.T., Pehmøller, C., Kristensen, J.M., Kjøbsted, R., Birk, J.B., Schjerling, P., Richter, E.A., Goodyear, L.J., Wojtaszewski, J.F.P., J. Physiol., 592, 2014, 351.
24. 24 Marcinko, K., Steinberg, G.R., Exp. Physiol., 99, 2014, 1581.
25. 25 Crawford, S.A., Costford, S.R., Aguer, C., Thomas, S.C., deKemp, R.A., DaSilva, J.N., Lafontaine, D., Kendall, M., Dent, R., Beanlands, R.S., McPherson, R., Harper, M.E., Diabetologia, 53, 2010, 1986.
26. 26 Milan, D., Jeon, J.T., Looft, C., Amarger, V., Robic, A., Thelander, M., Rogel-Gaillard, C., Paul, S., Iannuccelli, N., Rask, L., Ronne, H., Lundstrom, K., Reinsch, N., Gellin, J., Kalm, E., Roy, P.L., Chardon, P., Andersson, L., Science, 288, 2000, 1248.
27. 27 Barnes, B.R., Glund, S., Long, Y.C., Hjalm, G., Andersson, L., Zierath, J.R., FASEB J., 19, 2005, 773.
28. 28 Barnes, B.R., Marklund, S., Steiler, T.L., Walter, M., Hjalm, G., Amarger, V., Mahlapuu, M., Leng, Y., Johansson, C., Galuska, D., Lindgren, K., Abrink, M., Stapleton, D., Zierath, J.R., Andersson, L., J. Biol. Chem., 279, 2004, 38441.
29. 29 Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., Viollet, B., J. Clin. Invest., 120, 2010, 2355.
30. 30 Fullerton, M.D., Curr. Opin. Lipidol., 27, 2016, 172.
31. 31 Bijland, S., Mancini, S.J., Salt, I.P., Clin. Sci., 124, 2013, 491.
32. 32 Xu, X.J., Gauthier, M.S., Hess, D.T., Apovian, C.M., Cacicedo, J.M., Gokce, N., Farb, M., Valentine, R.J., Ruderman, N.B., J. Lipid Res., 53, 2012, 792.
33. 33 Ford, R.J., Fullerton, M.D., Pinkosky, S.L., Day, E.A., Scott, J.W., Oakhill, J.S., Bujak, A.L., Smith, B.K., Crane, J.D., Blümer, R.M., Marcinko, K., Kemp, B.E., Gerstein, H.C., Steinberg, G.R., Biochem. J., 468, 2015, 125.
34. 34 Fullerton, M.D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.P., O'Neill, H.M., Ford, R.J., Palanivel, R., O'Brien, M., Hardie, D.G., Macaulay, S.L., Schertzer, J.D., Dyck, J.R.B., vanDenderen, B.J., Kemp, B.E., Steinberg, G.R., Nat. Med., 19, 2013, 1649.
35. 35 Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M.F., Goodyear, L.J., Moller, D.E., J. Clin. Invest., 108, 2001, 1167.
36. 36 Gaidhu, M.P., Bikopoulos, G., Ceddia, R.B., Am. J. Physiol. Cell Physiol., 303, 2012, C1192.
37. 37 Yin, W., Mu, J., Birnbaum, M.J., J. Biol. Chem., 278, 2003, 43074.
38. 38 Koh, H.J., Hirshman, M.F., He, H., Li, Y., Manabe, Y., Balschi, J.A., Goodyear, L.J., Biochem. J., 403, 2007, 473.
39. 39 Mottillo, E.P., Desjardins, E.M., Crane, J.D., Smith, B.K., Green, A.E., Ducommun, S., Henriksen, T.I., Rebalka, I.A., Razi, A., Sakamoto, K., Scheele, C., Kemp, B.E., Hawke, T.J., Ortega, J., Granneman, J.G., Steinberg, G.R., Cell Metab., 24, 2016, 118.
40. 40 Dasgupta, B., Chhipa, R.R., Trends Pharmacol. Sci., 37, 2016, 192.
41. 41 Faubert, B., Vincent, E.E., Poffenberger, M.C., Jones, R.G., Cancer Lett., 356, 2015, 165.
42. 42 Hardie, D.G., Clin. Cancer Res., 21, 2015, 3836.
43. 43 Zadra, G., Batista, J.L., Loda, M., Mol. Cancer Res., 13, 2015, 1059.
44. 44 Foretz, M., Guigas, B., Bertrand, L., Pollak, M., Viollet, B., Cell Metab., 20, 2014, 953.
45. 45 Hardie, D.G., Genes Dev., 25, 2011, 1895.
46. 46 Ducommun, S., Deak, M., Sumpton, D., Ford, R.J., Nunez Galindo, A., Kussmann, M., Viollet, B., Steinberg, G.R., Foretz, M., Dayon, L., Morrice, N.A., Sakamoto, K., Cell. Signal., 27, 2015, 978.
47. 47 Toyama, E.Q., Herzig, S., Courchet, J., Lewis, T.L. Jr., Loson, O.C., Hellberg, K., Young, N.P., Chen, H., Polleux, F., Chan, D.C., Shaw, R.J., Science, 351, 2016, 275.
48. 48 Ruderman, N.B., Carling, D., Prentki, M., Cacicedo, J.M., J. Clin. Invest., 123, 2013, 2764.
49. 49 Decleves, A.E., Zolkipli, Z., Satriano, J., Wang, L., Nakayama, T., Rogac, M., Le, T.P., Nortier, J.L., Farquhar, M.G., Naviaux, R.K., Sharma, K., Kidney Int., 85, 2014, 611.
50. 50 Mount, P.F., Power, D.A., J. Pathol., 237, 2015, 407.
51. 51 Garcia-Prieto, C.F., Gil-Ortega, M., Aranguez, I., Ortiz-Besoain, M., Somoza, B., Fernandez-Alfonso, M.S., Vascul. Pharmacol., 67–69, 2015, 10.
52. 52 Kim, T.T., Dyck, J.R., Trends Endocrinol. Metab., 26, 2015, 40.
53. 53 O'Neill, L.A.J., Grahame Hardie, D., Nature, 493, 2013, 346.
54. 54 Rana, S., Blowers, E.C., Natarajan, A., J. Med. Chem., 58, 2015, 2.
55. 55 Porto, A.G., Brun, F., Severini, G.M., Losurdo, P., Fabris, E., Taylor, M.R., Mestroni, L., Sinagra, G., Circ. Arrhythm. Electrophysiol., 9, 2016, e003121.
56. 56 Yavari, A., Stocker, C.J., Ghaffari, S., Wargent, E.T., Steeples, V., Czibik, G., Pinter, K., Bellahcene, M., Woods, A., Martinez de Morentin, P.B., Cansell, C., Lam, B.Y., Chuster, A., Petkevicius, K., Nguyen-Tu, M.S., Martinez-Sanchez, A., Pullen, T.J., Oliver, P.L., Stockenhuber, A., Nguyen, C., Lazdam, M., O'Dowd, J.F., Harikumar, P., Toth, M., Beall, C., Kyriakou, T., Parnis, J., Sarma, D., Katritsis, G., Wortmann, D.D., Harper, A.R., Brown, L.A., Willows, R., Gandra, S., Poncio, V., de Oliveira Figueiredo, M.J., Qi, N.R., Peirson, S.N., McCrimmon, R.J., Gereben, B., Tretter, L., Fekete, C., Redwood, C., Yeo, G.S., Heisler, L.K., Rutter, G.A., Smith, M.A., Withers, D.J., Carling, D., Sternick, E.B., Arch, J.R., Cawthorne, M.A., Watkins, H., Ashrafian, H., Cell Metab., 23, 2016, 821.
57. 57 Yang, X., Mudgett, J., Bou-About, G., Champy, M.F., Jacobs, H., Monassier, L., Pavlovic, G., Sorg, T., Herault, Y., Petit-Demouliere, B., Lu, K., Feng, W., Wang, H., Ma, L.J., Askew, R., Erion, M.D., Kelley, D.E., Myers, R.W., Li, C., Guan, H.P., J. Biol. Chem., 2016 ISSN 1083-351X.
58. 58 López, M., Nogueiras, R., Tena-Sempere, M., Diéguez, C., Nat. Rev. Endocrinol., 12, 2016, 421.
59. 59 Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R., Zhao, G., Marsh, K., Kym, P., Jung, P., Camp, H.S., Frevert, E., Cell Metab., 3, 2006, 403.
60. 60 Neumann, D., Woods, A., Carling, D., Wallimann, T., Schlattner, U., Protein Expr. Purif., 30, 2003, 230.
61. 61 Ward, J., Reyes, A., Kurumbail, R.G., Methods Enzymol., 2016 in press.
62. 62 El-Mir, M.Y., Nogueira, V., Fontaine, E., Averet, N., Rigoulet, M., Leverve, X., J. Biol. Chem., 275, 2000, 223.
63. 63 Lee, Y.S., Kim, W.S., Kim, K.H., Yoon, M.J., Cho, H.J., Shen, Y., Ye, J.M., Lee, C.H., Oh, W.K., Kim, C.T., Hohnen-Behrens, C., Gosby, A., Kraegen, E.W., James, D.E., Kim, J.B., Diabetes, 55, 2006, 2256.
64. 64 Vincent, M.F., Erion, M.D., Gruber, H.E., Van den Berghe, G., Diabetologia, 39, 1996, 1148.
65. 65 Young, M.E., Radda, G.K., Leighton, B., FEBS Lett., 382, 1996, 43.
66. 66 Gómez-Galeno, J.E., Dang, Q., Nguyen, T.H., Boyer, S.H., Grote, M.P., Sun, Z., Chen, M., Craigo, W.A., van Poelje, P.D., MacKenna, D.A., Cable, E.E., Rolzin, P.A., Finn, P.D., Chi, B., Linemeyer, D.L., Hecker, S.J., Erion, M.D., ACS Med. Chem. Lett., 1, 2010, 478.
67. 67 Hunter, R.W., Foretz, M., Bultot, L., Fullerton, M.D., Deak, M., Ross, F.A., Hawley, S.A., Shapiro, N., Viollet, B., Barron, D., Kemp, B.E., Steinberg, G.R., Hardie, D.G., Sakamoto, K., Chem. Biol., 21, 2014, 866.
68. 68 Langendorf, C.G., Ngoei, K.R., Scott, J.W., Ling, N.X., Issa, S.M., Gorman, M.A., Parker, M.W., Sakamoto, K., Oakhill, J.S., Kemp, B.E., Nat. Commun., 7, 2016, 10912.
69. 69 Moinet, M.; Marais, D.; Hallakou-Bozec, S.; Charon, C. WO 2,008,006,432, 2008.
70. 70 Zhao, G., Iyengar, R.R., Judd, A.S., Cool, B., Chiou, W., Kifle, L., Frevert, E., Sham, H., Kym, P.R., Bioorg. Med. Chem. Lett., 17, 2007, 3254.
71. 71 Moreno, D., Knecht, E., Viollet, B., Sanz, P., FEBS Lett., 582, 2008, 2650.
72. 72 Scott, J.W., van Denderen, B.J., Jorgensen, S.B., Honeyman, J.E., Steinberg, G.R., Oakhill, J.S., Iseli, T.J., Koay, A., Gooley, P.R., Stapleton, D., Kemp, B.E., Chem. Biol., 15, 2008, 1220.
73. 73 Treebak, J.T., Birk, J.B., Hansen, B.F., Olsen, G.S., Wojtaszewski, J.F., Am. J. Physiol. Cell Physiol., 297, 2009, C1041.
74. 74 Langendorf, C.G., Kemp, B.E., Cell Res., 25, 2015, 5.
75. 75 Sanders, M.J., Ali, Z.S., Hegarty, B.D., Heath, R., Snowden, M.A., Carling, D., J. Biol. Chem., 282, 2007, 32539.
76. 76 Mirguet, O., Sautet, S., Clement, C.A., Toum, J., Donche, F., Marques, C., Rondet, E., Pizzonero, M., Beaufils, B., Dudit, Y., Huet, P., Trottet, L., Grondin, P., Brusq, J.M., Boursier, E., Saintillan, Y., Nicodeme, E., Mirguet, O., Rondet, E., Pizzonero, M., ACS Med. Chem. Lett., 4, 2013, 632.
77. 77 Zadra, G., Photopoulos, C., Tyekucheva, S., Heidari, P., Weng, Q.P., Fedele, G., Liu, H., Scaglia, N., Priolo, C., Sicinska, E., Mahmood, U., Signoretti, S., Birnberg, N., Loda, M., EMBO Mol. Med., 6, 2014, 519.
78. 78 Cameron, K.O., Kung, D.W., Kalgutkar, A.S., Kurumbail, R.G., Miller, R., Salatto, C.T., Ward, J., Withka, J.M., Bhattacharya, S.K., Boehm, M., Borzilleri, K.A., Brown, J.A., Calabrese, M., Caspers, N.L., Cokorinos, E., Conn, E.L., Dowling, M.S., Edmonds, D.J., Eng, H., Fernando, D.P., Frisbie, R., Hepworth, D., Landro, J., Mao, Y., Rajamohan, F., Reyes, A.R., Rose, C.R., Ryder, T., Shavnya, A., Smith, A.C., Tu, M., Wolford, A.C., Xiao, J., J. Med. Chem., 59, 2016, 8068.
79. 79 Erion, M.D., Van Poelje, P.D., Mackenna, D.A., Colby, T.J., Montag, A.C., Fujitaki, J.M., Linemeyer, D.L., Bullough, D.A., J. Pharmacol. Exp. Ther., 312, 2005, 554.
80. 80 Scott, J.W., Galic, S., Graham, K.L., Foitzik, R., Ling, N.X., Dite, T.A., Issa, S.M., Langendorf, C.G., Weng, Q.P., Thomas, H.E., Kay, T.W., Birnberg, N.C., Steinberg, G.R., Kemp, B.E., Oakhill, J.S., Chem. Biol., 22, 2015, 705.
81. 81 Hawley, S.A., Fullerton, M.D., Ross, F.A., Schertzer, J.D., Chevtzoff, C., Walker, K.J., Peggie, M.W., Zibrova, D., Green, K.A., Mustard, K.J., Kemp, B.E., Sakamoto, K., Steinberg, G.R., Hardie, D.G., Science, 336, 2012, 918.
82. 82 Hardie, D.G., Diabetes, 62, 2013, 2164.
83. 83 Cravo, D.; Lepifre, F.; Hallakou-Bozec, S.; Charon, C. WO 2,009,124,636, 2009.
84. 84 Cravo, D.; Hallakou-Bozec, S.; Bolze, S.; Lepifre, F.; Faveriel, L.; Durand, J.-D.; Charon, C. WO 2,014,001,554, 2014.
85. 85 Daugan, A. C.; Lamotte, Y.; Mirguet, O. WO 2,012,119,978, 2012.
86. 86 Bouillot, A. M. J.; Daugan, A. C.; Lamotte, Y.; Mirguet, O. WO 2,012,119,979, 2012.
87. 87 Birnberg, N. C.; Liu, H.; Weng, Q. P.; Shang, H.; Yin, P.; Rajur, S. B.; Kim, H.-O.; Salgaonkar, P. D.; Peet, N. P. WO 2,009,100,130, 2009.
88. 88 Bhattacharya, S. K.; Cameron, K. O.; Dowling, M. S.; Ebner, D. C.; Fernando, D. P.; Filipski, K. J.; Kung, D. W.; Lee, E. C. Y.; Smith, A. C.; Tu, M. WO 2,013,153,479, 2013.
89. 89 Muzzin, P.; Lysek, R.; Garrouste, P. WO 2,014,128,549, 2014.
90. 90 Fett, E.; Mougenot, P.; Namane, C.; Nicolai, E.; Venier, O. WO 2,015,091,937, 2015.
91. 91 Madanahalli, R. R. J.; Gurram, R. M.; Pachiyappan, S. WO 2,014,202,580, 2014.
92. 92 Tamura, Y.; Kojima, E.; Ikemoto, H.; Hinata, Y. US 20,150,203,450, 2015.
93. 93 Bookser, B. C.; Dang, Q.; Gibson, T. S.; Jiang, H.; Chung, D. M.; Bao, J.; Jiang, J.; Kassick, A.; Kekec, A.; Lan, P.; Lu, H.; Makara, G. M.; Romero, F. A.; Sebhat, I.; Wilson, D.; Wodka, D. WO 2,010,036,613, 2010.
94. 94 Bookser, B. C.; Dang, Q.; Gibson, T. S.; Jiang, H.; Chung, D. C.; Bao, J.; Jiang, J.; Kassick, A.; Kekec, A.; Lan, P.; Lu, H.; Makara, G. M.; Romero, F. A.; Sebhat, I.; Wilson, D.; Wodka, D. WO 2,010,047,982, 2010.
95. 95 Anand, R.; Apgar, J. M.; Biftu, T.; Chen, P.; Chu, L.; Colandrea, V. J.; Dong, G.; Dropinski, J.F.; Feng, D.; Hicks, J. D.; Jiang, J.; Kim, A. J.; Leavitt, K. J.; Li, B.; Qian, X.; Sebhat, I.; Wei, L.; Wilkening, R.R.; Wu, Z. WO 2,012,116,145, 2012.
96. 96 Tonogaki, K.; Ino, A.; Kojima, E.; Katou, M.; Iwatsu, M.; Tanaka, N.; Fujioka, M. US 20,130,184,240, 2013.
97. 97 Kojima, E.; Tonogaki, K.; Tanaka, N.; Katou, M.; Ino, A.; Iwatsu, M.; Fujioka, M.; Hinata, Y.; Ohyabu, N. US 20,140,194,420, 2014.
98. 98 Apgar, J. M.; Arasappan, A.; Biftu, T.; Chen, P.; Feng, D.; Guidry, E.; Hicks, J.; Kekec, A.; Leavitt, K.; Li, B.; Mccracken, T.; Sebhat, I.; Qian, X.; Wei, L.; Wilkening, R.; Wu, Z. WO 2,014,031,515, 2014.
99. 99 Apgar, J. M.; Biftu, T.; Chen, P.; Feng, D.; Hicks, J. D.; Kekec, A.; Leavitt, K. J.; Li, B.; Sebhat, I.; Qian, X.; Wei, L.; Wilkening, R. R.; Wu, Z. WO 2,014,031,465, 2014.
100. 100 Himmelsbach, F.; Langkopf, E.; Wagner, H. WO 2,015,007,669, 2015.
101. 101 Muzerelle, M.; Lysek, R.; Bellocq, N.; Lang, M. WO 2,016,001,224, 2016.
102. 102 Scott, J.W., Oakhill, J.S., Ling, N.X., Langendorf, C.G., Foitzik, R.C., Kemp, B.E., Issinger, O.G., Biochem. Biophys. Res. Commun., 443, 2014, 435.
103. 103 Pang, T., Zhang, Z.S., Gu, M., Qiu, B.Y., Yu, L.F., Cao, P.R., Shao, W., Su, M.B., Li, J.Y., Nan, F.J., Li, J., J. Biol. Chem., 283, 2008, 16051.
104. 104 Jensen, T.E., Ross, F.A., Kleinert, M., Sylow, L., Knudsen, J.R., Gowans, G.J., Hardie, D.G., Richter, E.A., Biochem. J., 467, 2015, 461.
105. 105 Yu, L.F., Li, Y.Y., Su, M.B., Zhang, M., Zhang, W., Zhang, L.N., Pang, T., Zhang, R.T., Liu, B., Li, J.Y., Li, J., Nan, F.J., ACS Med. Chem. Lett., 4, 2013, 475.
106. 106 Chen, L.; Feng, L.; Huang, M.; Liu, Y.; Wu, G.; Wu, J. Z.; Zhou, M. WO 2,011,128,251, 2011.
107. 107 Chen, L.; Feng, L.; He, Y.; Huang, M.; Liu, Y.; Yun, H.; Zhou, M. WO 2,012,001,020, 2012.
108. 108 Feng, F.; Huang, M.; Liu, Y.; Wu, G.; Zhou, M. WO 2,012,052,372, 2012.
109. 109 https://clinicaltrials.gov/ct2/show/NCT02286882?term=PF-06409577&rank=1.
110. 110 http://www.poxel.com/pdf/20160620_PXL770%20Phase%201%20Data_English.pdf.