Discovery of AZD8931, an equipotent, reversible inhibitor of signaling by EGFR, HER2, and HER3 receptors

ACS Medicinal Chemistry Letters

Volumn 4, Issue 8, 2013, Pages 742-746

  Barlaam, Bernard ^a   Anderton, Judith ^a   Ballard, Peter ^a   Bradbury, Robert H ^a   Hennequin, Laurent F A ^a,c   Hickinson, D Mark ^a   Kettle, Jason G ^a   Kirk, George ^a   Klinowska, Teresa ^a   Lambert Van Der Brempt, Christine ^a   Trigwell, Cath ^a   Vincent, John ^a   Ogilvie, Donald ^a,b  

^a ASTRAZENECA   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c Galderma R and D   (France)

Author keywords

AZD8931; HER receptor family; kinase inhibitor

Indexed keywords

AMIDE; AZD 8931; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; ERLOTINIB; VASCULOTROPIN RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER GROWTH; CANCER INHIBITION; CELL PROLIFERATION; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN TISSUE; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; PROTON TRANSPORT; RAT; STRUCTURE ACTIVITY RELATION;

EID: 84881459273     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400146c     Document Type: Article

References (24)

1. Olayioye, M. A.; Neve, R. M.; Lane, H. A.; Hynes, N. E. The ErbB signaling network: receptor heterodimerization in development and cancer EMBO J. 2000, 19, 3159-67
2. Jorissen, R. N.; Walker, F.; Pouliot, N.; Garrett, T. P.; Ward, C. W.; Burgess, A. W. Epidermal growth factor receptor: mechanisms of activation and signalling Exp. Cell. Res. 2003, 284, 31-53
3. Citri, A.; Skaria, K. B.; Yarden, Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3 Exp. Cell. Res. 2003, 284, 54-65
4. Salomon, D.; Gullick, W. The erbB family of receptors and their ligands: multiple targets for therapy Signal 2001, 2, 4-11
5. Ciardiello, F.; Tortora, G. EGFR antagonists in cancer treatment N. Engl. J. Med. 2008, 358, 1160-74
6. Schulze, W. X.; Deng, L.; Mann, M. Phosphotyrosine interactome of the ErbB-receptor kinase family Mol. Syst. Biol. 2005, 1, 2005.0008
7. Engelman, J. A.; Jänne, P. A.; Mermel, C. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 3788-93
8. Barker, A. J.; Gibson, K. H.; Grundy, W.; Godfrey, A. A.; Barlow, J. J.; Healy, M. P.; Woodburn, J. R.; Ashton, S. E.; Curry, B. J.; Scarlett, L.; Henthorn, L.; Richards, L. Studies leading to the identification of ZD1839 (Iressa): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer Bioorg. Med. Chem. Lett. 2001, 11, 1911-1914
9. Hennequin, L. F. A.; Ballard, P.; Boyle, F. T.; Delouvrie, B.; Ellston, R. P. A.; Halsall, C. T.; Harris, C. S.; Hudson, K.; Kendrew, J.; Pease, J. E.; Ross, H. S.; Smith, P.; Vincent, J. L. Novel 4-anilinoquinazolines with C-6 carbon-linked side chains: Synthesis and structure-activity relationship of a series of potent, orally active, EGF receptor tyrosine kinase inhibitors Bioorg. Med. Chem. Lett. 2006, 16, 2672-2676
10. Ballard, P.; Bradbury, R. H.; Harris, C. S.; Hennequin, L. F. A.; Hickinson, M.; Kettle, J. G.; Kendrew, J.; Klinowska, T.; Ogilvie, D. J.; Pearson, S. E.; Williams, E. J.; Wilson, I. Inhibitors of epidermal growth factor receptor tyrosine kinase: Optimization of potency and in vivo pharmacokinetics Bioorg. Med. Chem. Lett. 2006, 16, 4908-4912
11. Ballard, P.; Bradbury, R. H.; Harris, C. S.; Hennequin, L. F. A.; Hickinson, M.; Johnson, P. D.; Kettle, J. G.; Klinowska, T.; Leach, A. G.; Morgentin, R.; Pass, M.; Ogilvie, D. J.; Olivier, A.; Warin, N.; Williams, E. J. Inhibitors of epidermal growth factor receptor tyrosine kinase: Novel C-5 substituted anilinoquinazolines designed to target the ribose pocket Bioorg. Med. Chem. Lett. 2006, 16, 1633-1637
12. Ballard, P.; Bradbury, R. H.; Hennequin, L. F. A.; Hickinson, D. M.; Johnson, P. D.; Kettle, J. G.; Klinowska, T.; Morgentin, R.; Ogilvie, D. J.; Olivier, A. 5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase Bioorg. Med. Chem. Lett. 2005, 15, 4226-4229
13. Ballard, P.; Barlaam, B. C.; Bradbury, R. H.; Dishington, A.; Hennequin, L. F. A.; Hickinson, D. M.; Hollingsworth, I. M.; Kettle, J. G.; Klinowska, T.; Ogilvie, D. J.; Pearson, S. E.; Scott, J. S.; Suleman, A.; Whittaker, R.; Williams, E. J.; Wood, R.; Wright, L. Neutral 5-substituted 4- anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase Bioorg. Med. Chem. Lett. 2007, 17, 6326-6329
14. Barlaam, B.; Ballard, P.; Bradbury, R. H.; Ducray, R.; Germain, H.; Hickinson, D. M.; Hudson, K.; Kettle, J. G.; Klinowska, T.; Magnien, F.; Ogilvie, D. J.; Olivier, A.; Pearson, S. E.; Scott, J. S.; Suleman, A.; Trigwell, C. B.; Vautier, M.; Whittaker, R. D.; Wood, R. A new series of neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase Bioorg. Med. Chem. Lett. 2008, 18, 674-678
15. Barlaam, B.; Acton, D. G.; Ballard, P.; Bradbury, R. H.; Cross, D.; Ducray, R.; Germain, H.; Hudson, K.; Klinowska, T.; Magnien, F.; Ogilvie, D. J.; Olivier, A.; Ross, H. S.; Smith, R.; Trigwell, C. B.; Vautier, M.; Wright, L. Neutral 5-substituted 4-indazolylaminoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase Bioorg. Med. Chem. Lett. 2008, 18, 1799-1803
16. Hickinson, D. M.; Klinowska, T.; Speake, G.; Vincent, J.; Trigwell, C.; Anderton, J.; Beck, S.; Marshall, G.; Davenport, S.; Callis, R.; Mills, E.; Grosios, K.; Smith, P.; Barlaam, B.; Wilkinson, R. W.; Ogilvie, D. AZD8931, an Equipotent, Reversible Inhibitor of Signaling by Epidermal Growth Factor Receptor, ERBB2 (HER2), and ERBB3: A Unique Agent for Simultaneous ERBB Receptor Blockade in Cancer Clin. Cancer Res. 2010, 16, 1159-1169
17. Previously described in Himmelsbach, F.; Jung, B.; Solca, F. Int. Pat. Appl. WO 2003082290.
18. Carter, C. A.; Kelly, R. J.; Giaccone, G. Small-molecule inhibitors of the human epidermal receptor family Expert Opin. Invest. Drugs 2009, 18, 1829-1842
19. Stamos, J.; Sliwkowski, M. X.; Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor J. Biol. Chem. 2002, 277, 46265-272
20. Allen, F. H. The Cambridge Structural Database: a quarter of a million crystal structures and rising Acta Crystallogr. 2002, B58, 380-388
21. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242
22. PDB code 3CGO: Buckley, G. M.; Ceska, T. A.; Fraser, J. L.; Gowers, L.; Groom, C. R.; Higueruelo, A. P.; Jenkins, K.; Mack, S. R.; Morgan, T.; Parry, D. M.; Pitt, W. R.; Rausch, O.; Richard, M. D.; Sabin, V. IRAK-4 inhibitors. Part II: a structure-based assessment of imidazo[1,2-a]pyridine binding Bioorg. Med. Chem. Lett. 2008, 18, 3291-3295
23. PDB code 2B55: Yue, E. W.; Higley, C. A.; Dimeo, S. V.; Carini, D. J.; Nugiel, D. A.; Benware, C.; Benfield, P. A.; Cox, S.; Burton, C. R.; Grafstrom, R. H.; Sharp, D. M.; Sisk, L. M.; Boylan, J. F.; Muckelbauer, J. K.; Smallwood, A. M.; Chen, H.; Chang, C.-H.; Seitz, S. P.; Trainor, G. L. Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 3. Structure activity relationships at C3(1,2) J. Med. Chem. 2002, 45, 5233-5248
24. PDB code 2R4B: Wood, E. R.; Shewchuk, L. M.; Ellis, B.; Brignola, P.; Brashear, R. L.; Caferro, T. R.; Dickerson, S. H.; Dickson, H. D.; Donaldson, K. H.; Gaul, M.; Griffin, R. J.; Hassell, A. M.; Keith, B.; Mullin, R.; Petrov, K. G.; Reno, M. J.; Rusnak, D. W.; Tadepalli, S. M.; Ulrich, J. C.; Wagner, C. D.; Vanderwall, D. E.; Waterson, A. G.; Williams, J. D.; White, W. L.; Uehling, D. E. 6-Ethynylthieno[3,2- d ]- and 6-ethynylthieno[2,3- d ]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 2773-78