Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Seow, Vernon ^a   Lim, Junxian ^a   Cotterell, Adam J ^a   Yau, Mei Kwan ^a   Xu, Weijun ^a   Lohman, Rink Jan ^a   Kok, W Mei ^a   Stoermer, Martin J ^a   Sweet, Matthew J ^a   Reid, Robert C ^a   Suen, Jacky Y ^a   Fairlie, David P ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C5A; COMPLEMENT COMPONENT C5A RECEPTOR; IMMUNOSUPPRESSIVE AGENT;

ANIMAL; ANTAGONISTS AND INHIBITORS; BIOAVAILABILITY; CHEMICAL STRUCTURE; CHEMISTRY; CHEMOTAXIS; CONFORMATION; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; EDEMA; HUMAN; IMMUNOLOGY; MACROPHAGE; MALE; METABOLISM; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MONOCYTE; RAT;

ANIMALS; BIOLOGICAL AVAILABILITY; CHEMOTAXIS; COMPLEMENT C5A; DISEASE MODELS, ANIMAL; EDEMA; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MACROPHAGES; MALE; MOLECULAR CONFORMATION; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; MONOCYTES; RATS; RECEPTOR, ANAPHYLATOXIN C5A;

EID: 84964402769     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep24575     Document Type: Article

References (46)

1. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computional approaches to estaimate solubility and permeability in drug discovery and development settings, Adv. Drug Delivery Rev. 23, 3-25 (1997).
2. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46, 3-26 (2001).
3. Veber, D. F., Johnson, S. R., Cheng, H. Y., Ward, B. R. & Kopple, K. D. Molecular properties that influences the oral bioavailability of drug candidates. J. Med. Chem. 45, 2615-2623 (2002).
4. Monk, P. N., Scola, A. M., Madala, P. & Fairlie, D. P. Function, structure and therapeutic potential of complement C5a receptors. Br. J. Pharmacol. 152, 429-448 (2007).
5. Lim, J. et al. C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling. FASEB J. 27, 822-831 (2013).
6. Seow, V. et al. Inflammatory responses induced by lipopolysaccharide are amplified in primary human monocytes but suppressed in macrophages by complement protein C5a. J. Immunol. 191, 4308-4316 (2013).
7. Markiewski, M. M. et al. Modulation of the antitumor immune response by complement. Nat. Immunol. 9, 1225-1235 (2008).
8. Vasrevu, S. K. et al. Complement C5a receptor facilitates cancer metastasis by altering T-cell responses in the metastic niche. Cancer. Res. 13, 3454-3465 (2014).
9. Guo, R. F. & Ward, P. A. Role of C5a in inflammatory responses. Annu. Rev. Immunol. 23, 821-852 (2005).
10. Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A. & Bell, L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat. Biotechnol. 25, 1256-1264 (2007).
11. Wong, A. K. et al. Small Molecular Probes for G-Protein-Coupled C5a Receptors: Conformationally Constrained Antagonists Derived from the C Terminus of the Human Plasma Protein C5a. J. Med. Chem. 41, 3417-3425 (1998).
12. Finch, A. M. et al. Low-molecular-weight peptidic and cyclic antagonists of the receptor for the complement factor C5a. J. Med. Chem. 42, 1965-1974 (1999).
13. March, D. R. et al. Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Mol. Pharmacol. 65, 868-879 (2004).
14. Sumichika, H. et al. Identification of a potent and orally active non-peptide C5a receptor antagonist. J. Biol. Chem. 277, 49403-49407 (2002).
15. Gong, Y. et al. Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists. Bioorg. Med. Chem. Lett. 18, 3852-3855 (2008).
16. Kawai, M. et al. Identification and synthesis of a receptor binding site of human anaphylatoxin C5a. J. Med. Chem. 34, 2068-2071 (1991).
17. Konteatis, Z. D. et al. Development of C5a receptor antagonists. Differential loss of functional responses. J. Immunol. 153, 4200-4204 (1994).
18. Wyllie, D. J. & Chen, P. E. Taking the time to study competitive antagonism. Br. J. Pharmacol. 150, 541-551 (2007).
19. Ward, A. P. The dark side of C5a in sepsis. Nat. Rev. Immuol. 4, 133-142 (2004).
20. Vauquelin, G. & Charlton, J. S. Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action. Br. J. Pharmacol. 3, 1476-5381 (2004).
21. Wu, B. et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 330, 1066-1071 (2010).
22. Higginbottom, A. et al. Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. J. Biol. Chem. 280, 17831-17840 (2005).
23. Boucard, A. A. et al. Constitutive activation of the angiotensin II type 1 receptor alters the spatial proximity of transmembrane 7 to the ligand-binding pocket. J. Biol. Chem. 278, 36628-36636 (2003).
24. Joseph, M. P., Maigret, B., Bonnafous, J. C., Marie, J. & Scheraga, H. A. A computer modeling postulated mechanism for angiotensin II receptor activation. J. Prot. Chem. 14, 381-398 (1995).
25. Miao, Y., Nichols, S. E., Gasper, P. M., Metzger, V. T. & McCammon, J. A. Activation and dynamic network of the M2 muscarine receptor. Proc. Natl. Acad. Sci. USA 110. 10982-10987 (2013).
26. Rosenbaum, D. M., Rasmussen, S. G. & Kobilka, B. K. The structure and function of G-protein-coupled receptors. Nature. 459, 356-363 (2009).
27. Gonzalez, A., Cordomi, A., Matsoukas, M., Zachmann, J. & Pardo, L. Modeling of G protein-coupled receptors using crystal structures: from monomers to signaling complexes. Adv. Exp. Med. Biol. 796, 15-33 (2014).
28. Klos, A. et al. The role of the anaphylatoxins in health and disease. Mol. Immunol. 46, 2753-2766 (2009).
29. Matthews, K. W., Mueller-Ortiz, S. L. & Wetsel, R. A. Carboxypeptidase N: A pleiotropic regulator of inflammation. Mol. Immunol. 40, 785-793 (2004).
30. Buck, E. & Wells, J. A. Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor. Proc. Natl. Acad. Sci. USA 102, 2719-2724 (2005).
31. Gonsiorek, W. et al. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J. Pharmacol. Exp. Ther. 322, 477-485 (2007).
32. Vauquelin, G. & Szczuka, A. Kinetic versus allosteric mechanisms to explain insurmountable antagonism and delayed ligand dissociation. Neurochem. Int. 51, 254-260 (2007).
33. Lu, H. & Tonge, P. J. Drug-target residence time: critical information for lead optimization. Curr. Opin. Chem. Biol. 14, 467-474 (2010).
34. Sanderson, K. Irreversible kinase inhibitors gain traction. Nat. Rev. Drug Discov. 12, 649-651 (2013).
35. Singh, J., Petter, R. C., Baillie, T. A. & Whitty, A. The resurgence of covalent drugs. Nature Rev. Drug Discov. 10, 307-317 (2011).
36. Copeland, R. A., Pompliano, D. L. & Meek, T. D. Drug-target residence time and its implications for lead optimization. Nat. Rev. Drug Discov. 5, 730-739 (2006).
37. Tummino, P. J. & Copeland, R. A. Residence Time of Receptor-Ligand Complexes and Its Effect on Biological Function. Biochemistry 47, 5481-5492 (2008).
38. Reid, R. C., Abbenante, G., Taylor, S. M. & Fairlie, D. P. A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug. J. Org. Chem. 68, 4464-4471 (2003).
39. Halai, R., Croker, D. E., Suen, J. Y., Fairlie, D. P. & Cooper, M. A. A Comparative study of impedance versus optical label-free systems relative to labelled assays in a predominantly G coupled GPCR (C5aR) signalling. Biosensors 2, 273-290 (2012).
40. Suen, J. Y. et al. Modulating human proteinase activated receptor 2 with a novel antagonist (GB88) and agonist (GB110). Br. J. Pharmacol. 165, 1413-1423 (2012).
41. Lohman, R. J. et al. An antagonist of human protease activated receptor-2 attenuates PAR2 signaling, macrophage activation, mast cell degranulation, and collagen-induced arthritis in rats. FASEB J. 26, 2877-2887 (2012).
42. Kilkenny, C., Browne, W. I., Cuthill, C., Emerson, M. & Altman, D. G. Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160, 1577-1579 (2010).
43. McGrath, J., Drummond, G., McLachlan, E., Kilkenny, C. & Wainwright, C. Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160, 1573-1576 (2010).
44. Isberg, V. et al. GPCRDB: an information system for G protein-coupled receptors. Nucleic. Acids. Res. 42, 422-425 (2014).
45. Benkert, P., Kunzli, M. & Schwede, T. QMEAN server for protein model quality estimation. Nucleic. Acids. Res. 37, W510-514 (2009).
46. Zhang, C., Liu, S. & Zhou, Y. Accurate and efficient loop selections by the DFIRE-based all-atom statistical potential. Protein. Sci. 13, 391-399 (2004).