Azaindole-based inhibitors of Cdc7 kinase: Impact of the Pre-DFG residue, Val 195

ACS Medicinal Chemistry Letters

Volumn 4, Issue 2, 2013, Pages 211-215

  Tong, Yunsong ^a   Stewart, Kent D ^b   Florjancic, Alan S ^a   Harlan, John E ^d   Merta, Philip J ^c   Przytulinska, Magdalena ^a   Soni, Nirupama ^a   Swinger, Kerren K ^b   Zhu, Haizhong ^d   Johnson, Eric F ^a   Shoemaker, Alexander R ^a   Penning, Thomas D ^a  

^a Cancer Research   (United States)

^b Structural Biology   (United States)

^c Lead Discovery   (United States)

^d ABBOTT LABORATORIES   (United States)

Author keywords

azaindole; Cdc7 kinase; pre DFG residue

Indexed keywords

AZAINDOLE DERIVATIVE; CELL DIVISION CYCLE 7 INHIBITOR; GLYCOGEN SYNTHASE KINASE 3BETA; INDOLE DERIVATIVE; METHIONINE; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROPHOBICITY; MOLECULAR MODEL; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY;

EID: 84873970591     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml300348c     Document Type: Article

References (25)

1. Sheridan, R. P.; Nam, K.; Mairov, V. N.; McMasters, D. R.; Cornell, W. D. QSAR Models for predicting the similarity in binding profiles for pairs of protein kinases and the variation of models between experimental data sets J. Chem. Inf. Model. 2009, 49, 1974-1985
2. Bousset, K.; Diffley, J. F. The Cdc7 protein kinase is required for origin firing during S phase Genes Dev. 1998, 12, 480-490
3. Jiang, W.; McDonald, D.; Hope, T. J.; Hunter, T. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication EMBO J. 1999, 18, 5703-5713
4. Kumagai, H.; Sato, N.; Yamada, M.; Mahony, D.; Seghezzi, W.; Lees, E.; Arai, K.; Masai, H. A novel growth- and cell cycle-regulatedprotein, ASK, activates human Cdc7-related kinase and is essentialfor G1/S transition in mammalian cells Mol. Cell. Biol. 1999, 19, 5083-5095
5. Montagnoli, A.; Bosotti, R.; Villa, F.; Rialland, M.; Brotherton, D.; Mercurio, C.; Berthelsen, J.; Santocanale, C. Drf1, a novel regulatory subunit for human Cdc7 kinase EMBO J. 2002, 2, 3171-3181
6. Chapman, J. W.; Johnston, L. H. The yeast gene, DBF4, essential for entry into S phase is cell cycle regulated Exp. Cell Res. 1989, 180, 419-428
7. Cho, W.-H.; Lee, Y.-J.; Kong, S.-I.; Hurwitz, J.; Lee, J.-K. CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein Proc. Natl. Acad. Sci. 2006, 103, 11521-11526
8. Montagnoli, A.; Valsasina, B.; Brotherton, D.; Troiani, S.; Rainoldi, S.; Tenca, P.; Molinari, A.; Santocanale, C. Identification of Mcm2 Phosphorylation Sites by S-phase-regulating Kinases J. Biol. Chem. 2006, 281, 10281-10290
9. Forsburg, S. L. Eukaryotic MCM proteins: Beyond replication initiation Microbiol. Mol. Biol. Rev. 2004, 68, 109-131
10. Bonte, D.; Lindvall, C.; Liu, H.; Dykema, K.; Furge, K.; Weinreich, M. Cdc7-Dbf4 kinase is overexpressed in multiple cancers and tumor cell lines and is correlated with p53 inactivation Neoplasia 2008, 10, 920-931
11. Hessa, G. F.; Dronga, R. F.; Weilanda, K. L.; Slightoma, J. L.; Sclafanib, R. A.; Hollingsworth, R. E. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines Gene 1998, 211, 133-140
12. Montagnoli, A.; Tenca, P.; Sola, F.; Carpani, D.; Brotherton, D.; Albanese, C.; Santocanale, C. Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells Cancer Res. 2004, 64, 7110-7116
13. Kim, J. M.; Kakusho, N.; Yamada, M.; Kanoh, Y.; Takemoto, N.; Masai, H. Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint Oncogene 2008, 27, 3475-3482
14. Lindvall, M.; McBride, C.; McKenna, M.; Gesner, T. G.; Yabannavar, A.; Wong, K.; Lin, S.; Walter, A.; Shafer, C. M. 3D Pharmacophore model-assisted discovery of novel CDC7 inhibitors ACS Med. Chem. Lett 2011, 2, 720-723
15. Swords, R.; Mahalingam, D.; O'Dwyer, M.; Santocanale, C.; Kelly, K.; Carew, J.; Giles, F. Cdc7 kinase; a new target for drug development Eur. J. Cancer 2010, 46, 33-40
16. Shafer, C. M.; Lindvall, M.; Bellamacina, C.; Gesner, T. G.; Yabannavar, A.; Jia, W.; Lin, S.; Walter, A. 4-(1H-Indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 4482-4485
17. Zhao, C.; Tovar, C.; Yin, X.; Xu, Q.; Todorov, I. T.; Vassilev, L. T.; Chen, L. Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 319-323
18. Ermoli, A.; Bargiotti, A.; Brasca, M. G.; Ciavolella, A.; Colombo, N.; Fachin, G.; Isacchi, A.; Menichincheri, M.; Molinari, A.; Montagnoli, A.; Pillan, A.; Rainoldi, S.; Riccardi Sirtori, F.; Sola, F.; Thieffine, S.; Tibolla, M.; Valsasina, B.; Volpi, D.; Santocanale, C.; Vanotti, E. Cell Division Cycle 7 Kinase Inhibitors: 1HPyrrolo[2,3-b]pyridines, Synthesis and Structure-Activity Relationships J. Med. Chem. 2009, 52, 4380-4390
19. Vanotti, E.; Amici, R.; Bargiotti, A.; Berthelsen, J.; Bosotti, R.; Ciavolella, A.; Cirla, A.; Cristiani, C.; D'Alessio, R.; Forte, B.; Isacchi, A.; Martina, K.; Menichincheri, M.; Molinari, A.; Montagnoli, A.; Orsini, P.; Pillan, A.; Roletto, F.; Scolaro, A.; Tibolla, M.; Valsasina, B.; Varasi, M.; Volpi, D.; Santocanale, C. Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships J. Med. Chem. 2008, 51, 487-501
20. Montagnoli, A.; Valsasina, B.; Croci, V.; Menichincheri, M.; Rainoldi, S.; Marchesi, V.; Tibolla, M.; Tenca, P.; Brotherton, D.; Albanese, C.; Patton, V.; Alzani, R.; Ciavolella, A.; Sola, F.; Molinari, A.; Volpi, D.; Avanzi, N.; Fiorentini, F.; Cattoni, M.; Healy, S.; Ballinari, D.; Pesenti, E.; Isacchi, A.; Moll, J.; Bensimon, A.; Vanotti, E.; Santocanale, C. A. Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity Nat. Chem. Biol. 2008, 4, 357-365
21. Menichincheri, M.; Albanese, C.; Alli, C.; Ballinari, D.; Bargiotti, A.; Caldarelli, M.; Ciavolella, A.; Cirla, A.; Colombo, M.; Colotta, F.; Croci, V.; D'Alessio, R.; D'Anello, M.; Ermoli, A.; Fiorentini, F.; Forte, B.; Galvani, A.; Giordano, P.; Isacchi, A.; Martina, K.; Molinari, A.; Moll, J. K.; Montagnoli, A.; Orsini, P.; Orzi, F.; Pesenti, E.; Pillan, A.; Roletto, F.; Scolaro, A.; Tatò, M.; Tibolla, M.; Valsasina, B.; Varasi, M.; Vianello, P.; Volpi, D.; Santocanale, C.; Vanotti, E. Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding J. Med. Chem. 2010, 53, 7296-7315
22. Woods, K. W.; Lai, C.; Miyashiro, J. M.; Tong, Y.; Florjancic, A. S.; Han, E. K.; Soni, N.; Shi, Y.; Lasko, L.; Leverson, J. D.; Johnson, E. F.; Shoemaker, A. R.; Penning, T. D. Aminopyrimidinone Cdc7 kinase inhibitors Bioorg. Med. Chem. Lett. 2012, 22, 1940-1943
23. Schlosser, M.; Rausis, T. The structural proliferation of 2,6-difluoropyridine through organometallic intermediates Eur. J. Org. Chem. 2004, 5, 1018-1024
24. Menichincheri, M.; Bargiotti, A.; Berthelsen, J.; Bertrand, J. A.; Bossi, R.; Ciavolella, A.; Cirla, A.; Cristiani, C.; Croci, V.; D'Alessio, R.; Fasolini, M.; Fiorentini, F.; Forte, B.; Isacchi, A.; Martina, K.; Molinari, A.; Montagnoli, A.; Orsini, P.; Orzi, F.; Pesenti, E.; Pezzetta, D.; Pillan, A.; Poggesi, I.; Roletto, F.; Scolaro, A.; Tato, M.; Tibolla, M.; Valsasina, B.; Varasi, M.; Volpi, D.; Santocanale, C.; Vanotti, E. First Cdc7 Kinase Inhibitors: Pyrrolopyridinones as Potent and Orally Active Antitumor Agents. 2. Lead Discovery J. Med. Chem. 2009, 52, 293-307
25. Huang, D.; Zhou, T.; Lafleur, K.; Nevado, C.; Caflisch, A. Kinase selectivity potential for inhibitors targeting the ATP binding site: A network analysis Bioinformatics 2010, 26, 198-204