Identification of inhibitors of checkpoint kinase 1 through template screening

Journal of Medicinal Chemistry

Volumn 52, Issue 15, 2009, Pages 4810-4819

  Matthews, Thomas P ^a   Klair, Suki ^b   Burns, Samantha ^a   Boxall, Kathy ^a   Cherry, Michael ^b   Fisher, Martin ^b   Westwood, Isaac M ^a   Walton, Michael I ^a   McHardy, Tatiana ^a   Cheung, Kwai Ming J ^a   Van Montfort, Rob ^a   Williams, David ^b   Aherne, G Wynne ^a   Garrett, Michelle D ^a   Reader, John ^b   Collins, Ian ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b Sareum Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHECKPOINT KINASE 1; PROTEIN P53; PURINE DERIVATIVE; STAUROSPORINE;

ARTICLE; BIOASSAY; CELL CYCLE; CELL STRAIN HT29; CONTROLLED STUDY; DNA DAMAGE; ENZYME INHIBITION; HUMAN; HUMAN CELL; MOLECULAR WEIGHT; X RAY CRYSTALLOGRAPHY;

DRUG EVALUATION, PRECLINICAL; HT29 CELLS; HUMANS; HYDROGEN BONDING; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68549096176     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900314j     Document Type: Article

References (59)

1. Walworth, N. Cell-cycle checkpoint kinases: checking in on the cell cycle. Curr. Opin. Cell Biol. 2000, 12, 697-704.
2. Bartek, J.; Lukas, J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 2003, 3, 421-429.
3. Luo, Y.; Leverson, J. D. New opportunities in chemosensitization and radiosensitization: modulating the DNA-damage response. Expert Rev. Anticancer Ther. 2005, 5, 333-342.
4. Bourdon, J.-C. p53 and its isoforms in cancer. Br. J. Cancer 2007, 97, 277-282.
5. Chen, Z.; Xiao, Z.; Chen, J.; Ng, S. C.; Sowin, T.; Sham, H.; Rosenberg, S.; Fesik, S.; Zhang, H. Human Chk1 expression is dispensable for somatic cell death and critical for sustaining G2 DNA damage checkpoint. Mol. Cancer Ther. 2003, 2, 543-548.
6. Bucher, N.; Britten, C. D. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br. J. Cancer 2008, 98, 523-528.
7. Chen, Z.; Xiao, X.; Gu, W.; Xue, J.; Bui, M. H.; Kovar, P.; Li, G.; Wang, G.; Tao, Z.-F.; Tong, Y.; Lin, N.-H.; Sham, H. L.; Wang, J. Y. J.; Sowin, T. J.; Rosenberg, S. H.; Zhang, H. Selective Chk1 inhibitors differentially sensitize p53-deficient cells to cancer therapeutics. Int. J. Cancer 2006, 119, 2784-2794.
8. Zhou, B. B.; Bartek, J. Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat. Rev. Cancer 2004, 4, 216-225.
9. Tse, A. N.; Carvajal, R.; Scwartz, G. K. Targeting checkpoint kinase 1 in cancer therapeutics. Clin. Cancer Res. 2007, 13, 1955-1960.
10. Lam, M. H.; Rosen, J. M. Chk1 versus Cdc25: chking one's levels of cellular proliferation. Cell Cycle 2004, 3, 1355-1357.
11. Xiao, Z.; Xue, J.; Sowin, T. J.; Zhang, H. Differential roles of checkpoint kinase 1, checkpoint kinase 2, and mitogen-activated protein kinase-activated protein kinase 2 in mediating DNA damage-induced cell cycle arrest: implications for cancer therapy. Mol. Cancer Ther. 2006, 5, 1935-1943.
12. Ganzeinelli, M.; Carrassa, L.; Crippa, F.; Tavecchio, M.; Broggini, M.; Damia, G. Checkpoint kinase 1 down-regulation by an inducible small interfering RNA expression system sensitized in vivo tumours to treatment with 5-fluorouracil. Clin. Cancer Res. 2008, 14, 5131-5141.
13. Collins, I.; Garrett, M. Inhibitors of the cell cycle. Curr. Opin. Pharmacol. 2005, 5, 366-373.
14. Tao, Z.-F.; Lin, N.-H. Chk1 inhibitors for novel cancer treatment. Anticancer Agents Med. Chem. 2006, 6, 377-388.
15. (a) Wang, G. T.; Li, G.; Mantei, R. A.; Chen, Z.; Kovar, P.; Gu, W.; Xiao, Z.; Zhang, H.; Sham, H. L.; Sowin, T.; Rosenberg, S. H.; Lin, N.-H. 1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent and selective inhibitors of Chk1 kinase: synthesis, preliminary SAR, and biological activities. J. Med. Chem. 2005, 48, 31118-3121.
16. (b) Tong, Y.; Claiborne, A.; Stewart, K. D.; Park, C.; Kovar, P.; Chen, Z.; Credo, R. B.; Gu,W.-Z.; Gwaltney, S. L.II; Judge, R. A.; Zhang, H.; Rosenberg, S. H.; Sham, H. L.; Sowin, T. J.; Lin, N. Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors. Bioorg. Med. Chem. 2007, 15, 2759-2767.
17. (c) Wang, L.; Sullivan, G. M.; Hexamer, L. A.; Hasvold, R. T.; Przytulinska, M.; Tao, Z.-F.; Li, G.; Chen, Z.; Xiao, Z.; Gu,W.-Z.; Xue, J.; Bui, M.-H.; Merta, P.; Kovar, P.; Bouska, J. J.; Zhang, H.; Park, C.; Stewart, K. D.; Sham, H. L.; Sowin, T. J.; Rosenberg, S. H.; Lin, N.-H. Design, synthesis and biological activity of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-one-based potent and selective Chk-1 inhibitors. J. Med. Chem. 2007, 50, 4162-4176.
18. (a) Huang, S.; Garbaccio, R. M.; Fraley, M. E.; Steen, J.; Kreatsoulas, C.; Hartmann, G.; Stirdivant, S.; Drakas, B.; Rickert, K.; Walsh, E.; Hamilton, K.; Buser, C. A.; Hardwick, J.; Mao, X.; Abrams, M.; Beck, S.; Tao, W.; Lobell, R.; Sepp-Lorenzino, L.; Yan, Y.; Ikuta, M.; Murphy, J. Z.; Sardana, V.; Munshi, S.; Kuo, L.; Reilly, M.; Mahan, E. Development of 6-substituted indolylquinolinones as potent Chek1 inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 5907-5912.
19. (b) Fraley, M. E.; Steen, J. T.; Brnardic, E. J.; Arrington, K. L.; Spencer, K. L.; Hanney, B. A.; Kim, Y.; Hartman, G. D.; Stirdivant, S. M.; Drakas, B. A.; Rickert, K.;Walsh, E. S.; Hamilton, K.; Buser, C. A.; Hardwick, J.; Tao,W.; Beck, S. C.; Mao, X.; Lobell, R. B.; Sepp-Lorenzino, L.; Yan, Y.; Ikuta, M.; Munshi, S. K.; Kuo, L. C.; Kreatsoulas, C. 3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6. Bioorg. Med. Chem. Lett. 2006, 16, 6049-6053.
20. Teng, M.; Zhu, J.; Johnson, M. D.; Chen, P.; Kornmann, J.; Chen, E.; Blasina, A.; Register, J.; Anderes, K.; Rogers, C.; Deng, Y.; Ninkovic, S.; Grant, S.; Hu, Q.; Lundgren, K.; Peng, Z.; Kania, R. S. Structure-based design and synthesis of (5-arylamino-2H-pyrazol-3-yl)-biphenyl-20,40-diols as novel and potent human CHK1 inhibitors. J. Med. Chem. 2007, 50, 5253-5256.
21. Tse, A.; Rendahl, K. G.; Sheikh, T.; Cheema, H.; Aardalen, K.; Embry, M.; Ma, S.; Moler, E. J.; Nie, Z. J.; Lopas de Menezes, D. E.; Hibner, B.; Gesner, T. G.; Schwartz, G. K. CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase 1 poisons in vitro and in vivo. Clin. Cancer Res. 2007, 13, 591-602.
22. Blasina, A.; Hallin, J.; Chen, E.; Arango, M. E.; Kraynov, E.; Register, J.; Gant, S.; Ninkovic, S.; Chen, P.; Nichols, T.; O'Connor, P.; Anderes, K. Breaching the DNA damage checkpoint with PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol. Cancer Ther. 2008, 7, 2394-2404.
23. Zabludoff, S. D.; Deng, C.; Grondine, M. R.; Sheehy, A. M.; Ashwell, S.; Caleb, B. L.; Green, S.; Haye, H. R.; Horn, C. L.; Janetka, J. W.; Liu, D.; Mouchet, E.; Ready, S.; Rosenthal, J. L.; Queva, C.; Schwartz, G. K.; Taylor, K. J.; Tse, A. N.; Walker, G. E.; White, A. M. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol. Cancer Ther. 2008, 7, 2955-2966.
24. Ashwell, S.; Zabludoff, S. DNA damage detection and repair pathways-recent advances with inhibitors of checkpoint kinases in cancer therapy. Mol. Cancer Ther. 2008, 14, 4032-4037.
25. Janetka, J. W.; Ashwell, S.; Zabludoff, S.; Lyne, P. Inhibitors of checkpoint kinases: from discovery to the clinic. Curr. Opin. Drug Discovery Dev. 2007, 10, 473-486.
26. Prudhomme,M. Novel CHK1 inhibitors. Recent Pat. Anti-Cancer Drug Discovery 2006, 1, 55-68.
27. Hénon, H.; Conchon, E.; Hugon, B.; Messaoudi, S.; Golsteyn, R. M.; Prudhomme, M. Pyrrolocarbazoles as checkpoint 1 kinase inhibitors. Anticancer Agents Med. Chem. 2008, 8, 577-597.
28. Lyne, P.D.;Kenny, P.W.; Cosgrove,D.A.;Deng, C.; Zabludoff, S.; Wendeloski, J. J.; Ashwell, S. Identification of compounds with nanomolar binding affinity for checkpoint kinase-1 using knowledge-based virtual screening. J.Med. Chem. 2004, 47, 1962-1968.
29. Foloppe, N.; Fisher, L .M.; Howes, R.; Potter, A.; Robertson, A. G. S.; Surgenor, A. E. Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening. Bioorg. Med. Chem. 2006, 14, 4792-4802.
30. Chen, P.; Luo, C.; Deng, Y.; Ryan, K.; Register, J.; Margosiak, S.; Tempczyk-Russell, A.; Nguyen, B.; Myers, P.; Lundgren, K.; Kan, C.-C.; O'Connor, P. M. The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. Cell 2000, 100, 681-692.
31. Jhoti, H.; Cleasby, A.; Verdonk, M.; Williams, G. Fragment-based screening using X-ray crystallography and NMR spectroscopy. Curr. Opin. Chem. Biol. 2007, 11, 485-493.
32. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection. Drug Discovery Today 2004, 9, 430-431.
33. Card, G. L.; Blasdel, L.; England, B. P.; Zhang, C.; Suzuki, Y.; Gillette, S.; Fong, D.; Ibrahim, P. N.; Artis, D. R.; Bollag, G.; Milburn, M. V.; Kim, S. H.; Schlessinger, J.; Zhang, K. Y.Afamily of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat. Biotechnol. 2005, 23, 184-186.
34. Collins, I.; Workman, P. New approaches to molecular cancer therapeutics. Nat. Chem. Biol. 2006, 2, 689-700.
35. Chemical Computing Group; http://www.chemcomp.com. Accessed on 24 June 2009.
36. Von Leoprechting, A.; Kumpf, R.; Menzel, S.; Reulle, D.; Griebel, R.; Valler, M. J.; Buttner, F. H. Miniaturization and validation of a high-throughput serine kinase assay using the AlphaScreen platform. J. Biomol. Screen. 2004, 9, 719-725.
37. Ryan,A. J.;Gray,N.M.;Lowe,P.N.;Chung,C.W.Effect of detergent on "promiscuous" inhibitors. J.Med. Chem. 2003, 46, 3448-3451.
38. Burns, S.; Travers, J.; Collins, I.; Rowlands, M. G.; Newbatt, Y.; Thompson, N.; Garrett, M. D.; Workman, P.; Aherne, W. Identification of small molecule inhibitors of protein kinase B (PKB) in an AlphaScreen high-throughput screen. J. Biomol. Screening 2006, 11, 822-827.
39. Babaoglu, K.; Shoichet, B. K. Deconstructing fragment-based inhibitor discovery. Nat. Chem. Biol. 2006, 2, 658-659.
40. Foloppe, N.; Fisher, L. M.; Francis, G.; Howes, R.; Kierstan, P.; Potter, A. Identification of a buried pocket for potent and selective inhibition of CHk1: Prediction and verification. Bioorg. Med. Chem. 2006, 14, 1792-1804.
41. (a) Gibson, A. E.; Arris, C. E.; Bentley, J.; Boyle, F. T.; Curtin, N. J.; Davies, T. G.; Endicott, J. A.; Golding, B. T.; Grant, S.; Griffin, R. J.; Jewsbury, P.; Johnson, L. N.; Mesguiche, V.; Newell, D. R.; Noble, M. E.; Tucker, J. A.; Whitfield, H. J. Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O (6)-substituted guanine derivatives. J. Med. Chem. 2002, 45, 3381-3393.
42. (b) Hardcastle, I. R.; Arris, C. E.; Bentley, J.; Boyle, F. T.; Chen, Y.; Curtin, N. J.; Endicott, J. A.; Gibson, A. E.; Golding, B. T.; Griffin, R. J.; Jewsbury, P.; Menyerol, J.; Mesguiche, V.; Newell, D. R.; Noble, M. E.; Pratt, D. J.; Wang, L. Z.; Whitfield, H. J. N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. J. Med. Chem. 2004, 47, 3710-3722.
43. (a) Donald, A.; McHardy, T.; Rowlands, M. G.; Hunter, L. K.; Davies, T. G.; Boyle, R. G.; Aherne, G. W.; Garrett, M. D.; Collins, I. Rapid evolution of 6-phenylpurine inhibitors of protein kinase B through structure-based design. J. Med. Chem. 2007, 50, 2289-2293.
44. (b) Caldwell, J. J.; Davies, T. G.; Donald, A.; McHardy, T.; Rowlands, M. G.; Aherne, G.W.; Hunter, L. K.; Taylor, K.; Ruddle, R.; Raynaud, F. I.; Verdonk, M.; Workman, P.; Garrett, M. D.; Collins, I. Identification of 4-(4-aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as selective inhibitors of protein kinase B through fragment elaboration. J. Med. Chem. 2008, 51, 2147-2157.
45. Shapiro, G. I. Cyclin-dependent kinase pathways as targets for cancer treatment. J. Clin. Oncol. 2006, 24, 1770-1783.
46. Xiao, Z.; Xue, J.; Gu, W.-Z.; Bui, M.; Li, G.; Tao, Z.-F.; Lin, N.-H.; Sowin, T. J.; Zhang, H. Cyclin B1 is an efficacy-predicting biomarker for Chk1 inhibitors. Biomarkers 2008, 13, 579-596.
47. Hoehn, H.; Denzel, T. 1H-Pyrazolo[3,4-b]pyridines. Patent Appl. DE2301268, 1973 ;
48. Chem. Abs. 1973, 79, 115578.
49. Misra, R. N.; Xiao, H.-Y.; Rawlins, D. B.; Shan, W.; Kellar, K. A.; Mulheron, J. G.; Sack, J. S.; Tokarski, J. S.; Kimball, S. D.; Webster, K. R. 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclindependent kinases: highly potent 2,6-difluorophenacyl analogues. Bioorg. Med. Chem. Lett. 2003, 13, 2405-2408.
50. Brenner, E.; Baldwin, R. M.; Tamagnan, G. Asymmetric synthesis of (+)-(S,S)-reboxetine via a new (S)-2-(hydroxymethyl)morpholine preparation. Org. Lett. 2005, 7, 937-939.
51. Parry, D.; Shanahan, F.; Davis, N.; Wiswell, D.; Seghezzi, W.; Pierce, R.; Hsieh, Y.; Paruch, K.; Guzi, T. Targeting the replication checkpoint with a potent and selective CHK1 inhibitor SCH 900776. Abstracts of the 100th AACR Annual Meeting, Denver, CO, April 18-29, 2009, paper 2490.
52. (a) Schirok, H.; Kast, R.; Figueroa-Perez, S.; Bennabi, S.; Gnoth, M. J.; Feurer, A.; Heckroth, H.; Thutewohl, M.; Paulsen, H.; Knorr, A.; Huetter, J.; Lobell, M.; Muenter, K.; Geiss, V.; Ehmke, H.; Lang, D.; Radtke, M.; Mittendorf, J.; Stasch, J. Design and synthesis of potent and selective azaindole-based Rho kinase (ROCK) inhibitors. ChemMedChem 2008, 3, 1893-1904.
53. (b) Dai, Y.; Hartandi, K.; Soni, N. B.; Pease, L. J.; Reuter, D. R.; Olson, A. M.; Osterling, D. J.; Doktor, S. Z.; Albert, D. H.; Bouska, J. J.; Glaser,K. B.; Marcotte, P. A.; Stewart, K. D.; Davidsen, S. K.; Michaelides, M. R. Identification of aminopyrazolopyridine ureas as potent VEGFR/ PDGFR multitargeted kinase inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 386-390.
54. (c) Lin, R.; Connolly, P. J.; Lu, Y.; Chiu, G.; Li, S.; Yu, Y.; Huang, S.; Li, X.; Emanuel, S. L.; Middleton, S. A.; Gruninger, R. H.; Adams, M.; Fuentes-Pesquera, A. R.; Greenberger, L. M. Synthesis and evaluation of pyrazolo[3,4-b]pyridine CDK1 inhibitors as antitumor agents. Bioorg. Med. Chem. Lett. 2007, 17, 4297-4302.
55. (d) Witherington, J.; Bordas, V.; Gaiba, A.; Garton, N. S.; Naylor, A.; Rawlings, A. D.; Slingsby,B. P.; Smith, D. G.; Takle, A. K.;Ward, R.W. 6-Aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorg. Med. Chem. Lett. 2003, 13, 3055-3057.
56. (e) Witherington, J.; Bordas, V.; Garland, S. L.; Hickey, D. M. B.; Ife, R. J.; Liddle, J.; Saunders, M.; Smith, D. G.;Ward, R.W. 5-Aryl-pyrazolo[3,4-b] pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorg. Med. Chem. Lett. 2003, 13, 1577-1580.
57. (f) Misra, R. N.; Rawlins, D. B.; Xiao, H.; Shan, W.; Bursuker, I.; Kellar, K. A.; Mulheron, J. G.; Sack, J. S.; Tokarski, J. S.; Kimball, S. D.;Webster,K. R. 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136.
58. Collins, I.; Reader, J. C.; Cheung, K. M.; Matthews, T. P.; Proisy, N.; Klair, S. S. Patent Appl. WO2008075007, 2008;
59. Chem. Abstr. 2008, 149, 104737.