Identification of a novel and selective series of Itk inhibitors via a template-hopping strategy

ACS Medicinal Chemistry Letters

Volumn 4, Issue 10, 2013, Pages 948-952

  Alder, Catherine M ^a   Ambler, Martin ^a   Campbell, Amanda J ^a   Champigny, Aurelie C ^a   Deakin, Angela M ^a   Harling, John D ^a   Harris, Carol A ^a   Longstaff, Tim ^a   Lynn, Sean ^a   Maxwell, Aoife C ^a   Mooney, Chris J ^a   Scullion, Callum ^a   Singh, Onkar M P ^a   Smith, Ian E D ^a   Somers, Donald O ^a   Tame, Christopher J ^a   Wayne, Gareth ^a   Wilson, Caroline ^a   Woolven, James M ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

aminobenzothiazole; Interleukin 2 inducible tyrosine kinase; Itk; kinase inhibitors; kinase selectivity; template hopping

Indexed keywords

AURORA A KINASE; AURORA B KINASE; BENZOTHIAZOLE DERIVATIVE; GAMMA INTERFERON; INTERLEUKIN 2 INDUCIBLE TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; ASTHMA; BINDING SITE; CELL ASSAY; CELL CYCLE REGULATION; CRYSTAL STRUCTURE; DRUG IDENTIFICATION; DRUG SCREENING; DRUG SELECTIVITY; ENZYME ASSAY; ENZYME INHIBITION; HINGE REGION; HYDROGEN BOND; IC 50; MOLECULAR WEIGHT; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; T LYMPHOCYTE; X RAY CRYSTALLOGRAPHY;

EID: 84884764926     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400206q     Document Type: Article

References (22)

1. Grasis, J. A.; Tsoukas, C. D. Itk: The rheostat of the T cell response J. Signal Transduction 2011, 267868
2. August, A.; Ragin, M. J. Regulation of T-cell responses and diseases by Tec kinase Itk Int. Rev. Immumol. 2012, 31, 155-165
3. Das, J.; Furch, J. A.; Liu, C.; Moquin, R. V.; Lin, J.; Spergel, S. H.; McIntyre, K. W.; Shuster, D. J.; O'Day, K. D.; Penhallow, B.; Hung, C. Y.; Doweyko, A. M.; Kamath, A.; Zhang, H.; Marathe, P.; Kanner, S. B.; Lin, T. A.; Dodd, J. H.; Barrish, J. C.; Wityak, J. Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors Bioorg. Med. Chem. Lett. 2006, 16, 3706-3712
4. Riether, D.; Zindell, R.; Kowalski, J. A.; Cook, B. N.; Bentzien, J.; Lombaert, S. D.; Thomson, D.; Kugler, S. Z., Jr.; Skow, D.; Martin, L. S.; Raymond, E. L.; Khine, H. H.; O'Shea, K.; Woska, J. R., Jr.; Jeanfavre, D.; Sellati, R.; Ralph, K. L.; Ahlberg, J.; Labissiere, G.; Kashem, M. A.; Pullen, S. S.; Takahashi, H. 5-Aminomethylbenzimidazoles as potent ITK antagonists Bioorg. Med. Chem. Lett. 2009, 19, 1588-1591
5. Charrier, J. D.; Miller, A.; Kay, D. P.; Brenchley, G.; Twin, H. C.; Collier, P. N.; Ramaya, S.; Keily, S. B.; Durrant, S. J.; Knegtel, R. M.; Tanner, A. J.; Brown, K.; Curnock, A. P.; Jimenez, J. M. Discovery and structure-activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors J. Med. Chem. 2011, 54, 2341-2350
6. Zapf, C. W.; Gerstenberger, B. S.; Xing, L.; Limburg, D. C.; Anderson, D. R.; Caspers, N.; Han, S.; Aulabaugh, A.; Kurumbail, R.; Shakya, S.; Li, X.; Spaulding, V.; Czerwinski, R. M.; Seth, N.; Medley, Q. G. Covalent inhibitors of interleukin-2 inducible T-cell kinase (Itk) with nanomolar potency in a whole-blood assay J. Med. Chem. 2012, 55, 10047-10063
7. Lo, H. Y. Itk inhibitors: a patent review Expert Opin. Ther. Patents 2010, 20, 459-469
8. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9, 430-431
9. Erlanson, D. A.; McDowell, R. S.; O'Brien, T. Fragment-based drug discovery J. Med. Chem. 2004, 47, 3463-3482
10. Congreve, M.; Chessari, G.; Tisi, D.; Woodhead, A. J. Recent developments in fragment-based drug discovery J. Med. Chem. 2008, 51, 3661-3680
11. Scott, D. E.; Coyne, A. G.; Hudson, S. A.; Abell, C. Fragment-based approaches in drug discovery and chemical biology Biochemistry 2012, 51, 4990-5003
12. Bamborough, P.; Brown, M. J.; Christopher, J. A.; Chung, C.; Mellor, G. W. Selectivity of kinase inhibitor fragments J. Med. Chem. 2011, 54, 5131-5143
13. Hancock, A. A.; Bush, E. N.; Stanisic, D.; Kyncl, J. J.; Lin, C. T. Data normalization before statistical analysis: keeping the horse before the cart Trends Pharmacol. Sci. 1998, 9, 29-32
14. Fauq, A. H.; Singh, R. P.; Meshri, D. T. Encyclopedia of Reagents for Organic Synthesis; Wiley & Sons: New York, 2006.
15. Alder, C. M.; Baldwin, I. R.; Barton, N. P.; Campbell, A. J.; Champigny, A. C.; Harling, J. D.; Maxwell, A. C.; Simpson, J. K.; Smith, I. E. D.; Tame, C. J. Preparation of Pyrimidine Derivatives As Itk Kinase Inhibitors. WO 2010/106016 A1.
16. Kelly, K. R.; Ecsedy, J.; Mahalingam, D.; Nawrocki, S. T.; Padmanabhan, S.; Giles, F. J.; Carew, J. S. Targeting Aurora kinases in cancer treatment Curr. Drug Targets 2011, 12, 2067-2078
17. Carmena, M.; Earnshaw, W. C. The cellular geography of aurora kinases Nat. Rev. Mol. Cell. Biol. 2003, 4, 842-854
18. Glide, version 4.5; Schrödinger, LLC: New York, 2007.
19. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22, 3099-3108
20. Upstate kinase panel now part of Millipore; http://www.millipore.com/ life-sciences/flx4/lead-discovery.
21. Nowakowski, J.; Cronin, C. N.; McRee, D. E.; Knuth, M. W.; Nelson, C. G.; Pavletich, N. P.; Rogers, J.; Sang, B.-C.; Scheibe, D. N.; Swanson, R. V.; Thompson, D. A. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography Structure 2002, 10, 1659-1667
22. Coumar, M. S.; Leou, J.-S.; Shukla, P.; Wu, J.-S.; Dixit, A. K.; Lin, W.-H.; Chang, C.-Y.; Lien, T.-W.; Tan, U.-K.; Chen, C.-H.; Hsu, J. T-A.; Chao, Y.-S.; Wu, S.-Y.; Hsieh, H.-P. Structure-based drug design of novel aurora kinase A inhibitors: Structural basis for potency and specificity J. Med. Chem. 2009, 52, 1050-1062