Systematic exploration of dual-acting modulators from a combined medicinal chemistry and biology perspective

Journal of Medicinal Chemistry

Volumn 56, Issue 3, 2013, Pages 1197-1210

  Bornot, Aurelie ^a   Bauer, Udo ^b   Brown, Alastair ^a   Firth, Mike ^a   Hellawell, Caroline ^a   Engkvist, Ola ^b  

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLECYSTOKININ RECEPTOR; GHRELIN RECEPTOR; HORMONE RECEPTOR; IBUTAMOREN; MITEMCINAL; MOTILIN RECEPTOR; NEUROKININ 1 RECEPTOR; OPIATE RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG MECHANISM; DRUG TARGETING; GASTROINTESTINAL DISEASE; METHODOLOGY; PHARMACOPHORE; PHYSICAL CHEMISTRY; PROBABILITY;

CHEMISTRY, PHARMACEUTICAL; DRUG DISCOVERY; RECEPTORS, CHOLECYSTOKININ; RECEPTORS, NEUROKININ-1; RECEPTORS, OPIOID;

EID: 84873898165     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301653f     Document Type: Article

References (62)

1. Morgan, S.; Grootendorst, P.; Lexchin, J.; Cunningham, C.; Greyson, D. The cost of drug development: a systematic review Health Policy 2011, 100, 4-17
2. Hopkins, A. L. Network pharmacology: the next paradigm in drug discovery Nat. Chem. Biol. 2008, 4, 682-690
3. Wishart, D. S.; Knox, C.; Guo, A. C.; Cheng, D.; Shrivastava, S.; Tzur, D.; Gautam, B.; Hassanali, M. DrugBank: a knowledgebase for drugs, drug actions and drug targets Nucleic Acids Res. 2008, 36, D901-906
4. YildIrIm, M. A.; Goh, K. I.; Cusick, M. E.; Barabási, A. L.; Vidal, M. Drug-target network Nat. Biotechnol. 2007, 25, 1119-1126
5. Mestres, J.; Gregori-Puigjane, E.; Valverde, S.; Sole, R. V. Data completeness-the Achilles heel of drug-target networks Nat. Biotechnol. 2008, 26, 983-984
6. Jalencas, X.; Mestres, J. On the origins of drug polypharmacology Med. Chem. Commun. 2013, 4, 80-87
7. Benson, S. C.; Pershadsingh, H. A.; Ho, C. I.; Chittiboyina, A.; Desai, P.; Pravenec, M.; Qi, N.; Wang, J.; Avery, M. A.; Kurtz, T. W. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity Hypertension 2004, 43, 993-1002
8. Benndorf, R. A.; Rudolph, T.; Appel, D.; Schwedhelm, E.; Maas, R.; Schulze, F.; Silberhorn, E.; Boger, R. H. Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension Metabolism 2006, 55, 1159-1164
9. Peters, J. U., Ed. Polypharmacology in Drug Discovery; Wiley: Hoboken, NJ, 2012.
10. Morphy, J. R.; Harris, C. J. Designing Multi-Target Drugs; Royal Society of Chemistry: Cambridge, U.K., 2012.
11. Van der Schyf, C. J. The use of multi-target drugs in the treatment of neurodegenerative diseases Expert Rev. Clin. Pharmacol. 2011, 4, 293-298
12. Morphy, R.; Rankovic, Z. Designing multiple ligands-medicinal chemistry strategies and challenges Curr. Pharm. Des. 2009, 15, 587-600
13. Costantino, L.; Barlocco, D. Designed multiple ligands: basic research vs clinical outcomes Curr. Med. Chem. 2012, 19, 3353-3387
14. Wang, Y.; Xiao, J.; Suzek, T. O.; Zhang, J.; Wang, J.; Zhou, Z.; Han, L.; Karapetyan, K.; Dracheva, S.; Shoemaker, B. A.; Bolton, E.; Gindulyte, A.; Bryant, S. H. PubChem's BioAssay Database Nucleic Acids Res. 2012, 40, D400-D412
15. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B.; Overington, J. P. ChEMBL: a large-scale bioactivity database for drug discovery Nucleic Acids Res. 2012, 40, D1100-D1107
16. Krejsa, C. M.; Horvath, D.; Rogalski, S. L.; Penzotti, J. E.; Mao, B.; Barbosa, F.; Migeon, J. C. Predicting ADME properties and side effects: the BioPrint approach Curr. Opin. Drug Discovery Dev. 2003, 6, 470-480
17. GOSTAR (GVK BIO Online Structure Activity Relationship Database); GVK Biosciences Private Limited, S-1, Phase-1, T.I.E.: Hyderabad, A.P, India, 2010.
18. Fliri, A. F.; Loging, W. T.; Volkmann, R. A. Drug effects viewed from a signal transduction network perspective J. Med. Chem. 2009, 52, 8038-8046
19. Paolini, G. V.; Shapland, R. H.; van Hoorn, W. P.; Mason, J. S.; Hopkins, A. L. Global mapping of pharmacological space Nat. Biotechnol. 2006, 24, 805-815
20. Boran, A. D.; Iyengar, R. Systems approaches to polypharmacology and drug discovery Curr. Opin. Drug Discovery Dev. 2010, 13, 297-309
21. Maglott, D.; Ostell, J.; Pruitt, K. D.; Tatusova, T. Entrez Gene: gene-centered information at NCBI Nucleic Acids Res. 2011, 39, D52-D57
22. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890
23. Gleeson, M. P. Generation of a set of simple, interpretable ADMET rules of thumb J. Med. Chem. 2008, 51, 817-834
24. Patchett, A. A.; Nargund, R. P. Privileged structures-an update Annu. Rep. Med. Chem. 2000, 35, 289-298
25. Gloriam, D. E. Chemogenomics of allosteric binding sites in GPCRs. Drug Discovery Today: Technol. [Online eary access]. DOI: 10.1016/i.ddtec.2012.07. 010. Published Online: 2012.
26. Pang, M. H.; Kim, Y.; Jung, K. W.; Cho, S.; Lee, D. H. A series of case studies: practical methodology for identifying antinociceptive multi-target drugs Drug Discovery Today 2012, 17, 425-434
27. Bureeva, S.; Zvereva, S.; Romanov, V.; Serebryiskaya, T. Manual annotation of protein interactions Methods Mol. Biol. 2009, 563, 75-95
28. Inui, A. Ghrelin: an orexigenic and somatotrophic signal from the stomach Nat. Rev. Neurosci. 2001, 2, 551-560
29. Ohno, T.; Mochiki, E.; Kuwano, H. The roles of motilin and ghrelin in gastrointestinal motility Int. J. Pept. 2010, 2010, 820794
30. Bailey, J. M.; Scott, J. S.; Basilla, J. B.; Bolton, V. J.; Boyfield, I.; Evans, D. G.; Fleury, E.; Heightman, T. D.; Jarvie, E. M.; Lawless, K.; Matthews, K. L.; McKay, F.; Mok, H.; Muir, A.; Orlek, B. S.; Sanger, G. J.; Stemp, G.; Stevens, A. J.; Thompson, M.; Ward, J.; Vaidya, K.; Westaway, S. M. The discovery and optimisation of benzazepine sulfonamide and sulfones as potent agonists of the motilin receptor Bioorg. Med. Chem. Lett. 2009, 19, 6452-6458
31. Holzer, P. Opioid receptors in the gastrointestinal tract Regul. Pept. 2009, 155, 11-17
32. Shimizu, Y.; Matsuyama, H.; Shiina, T.; Takewaki, T.; Furness, J. B. Tachykinins and their functions in the gastrointestinal tract Cell. Mol. Life Sci. 2008, 65, 295-311
33. Walsh, S.; Heilig, M.; Nuzzo, A. P.; Henderson, P.; Lofwall, R. M. Effects of the NK(1) antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers. Addict. Biol. [Online early access]. DOI: 10.1111/j.1369-1600.2011.00419.x. Published Online: Jan 19, 2012
34. Vardanyan, R.; Kumirov, V. K.; Nichol, G. S.; Davis, P.; Liktor-Busa, E.; Rankin, D.; Varga, E.; Vanderah, T.; Porreca, F.; Lai, J.; Hruby, V. J. Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands Bioorg. Med. Chem. 2011, 19, 6135-6142
35. Ballet, S.; Feytens, D.; Buysse, K.; Chung, N. N.; Lemieux, C.; Tumati, S.; Keresztes, A.; Van Duppen, J.; Lai, J.; Varga, E.; Porreca, F.; Schiller, P. W.; Vanden Broeck, J.; Tourwe, D. Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist J. Med. Chem. 2011, 54, 2467-2476
36. Rémond, G.; Portevin, B.; Bonnet, J.; Canet, E.; Regoli, D.; DeNanteuil, G. Pharmacological profile of a novel series of NK1 antagonists. In vitro and in vivo potency of benzimidazolone derivatives Eur. J. Med. Chem. 1997, 32, 843-868
37. Agnes, R. S.; Lee, Y. S.; Davis, P.; Ma, S. W.; Badghisi, H.; Porreca, F.; Lai, J.; Hruby, V. J. Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors J. Med. Chem. 2006, 49, 2868-2875
38. Foran, S. E.; Carr, D. B.; Lipkowski, A. W.; Maszczynska, I.; Marchand, J. E.; Misicka, A.; Beinborn, M.; Kopin, A. S.; Kream, R. M. A substance P-opioid chimeric peptide as a unique nontolerance-forming analgesic Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 7621-7626
39. Morphy, R.; Rankovic, Z. Fragments, network biology and designing multiple ligands Drug Discovery Today 2007, 12, 156-160
40. Wermuth, C. G. Selective optimization of side activities: the SOSA approach Drug Discovery Today 2006, 11, 160-164
41. Martin, R. E.; Green, L. G.; Guba, W.; Kratochwil, N.; Christ, A. Discovery of the first nonpeptidic, small-molecule, highly selective somatostatin receptor subtype 5 antagonists: a chemogenomics approach J. Med. Chem. 2007, 50, 6291-6294
42. Gattrell, W. T.; Sambrook Smith, C. P.; Smith, A. J. An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors Bioorg. Med. Chem. Lett. 2012, 22, 2464-2469
43. Pipeline Pilot, version 7.5.2; Accelrys Software Inc.: San Diego, CA, 2008.
44. Spotfire Decision Site, version 9.1; TIBCO Software Inc.: Somerville, MA, 2007.
45. Rogers, D.; Hahn, M. Extended-connectivity fingerprints J. Chem. Inf. Model. 2010, 50, 742-754
46. Xia, X.; Maliski, E. G.; Gallant, P.; Rogers, D. Classification of kinase inhibitors using a Bayesian model J. Med. Chem. 2004, 47, 4463-4470
47. HUGO Gene Nomenclature Committee at the European Bioinformatics Institute. http://www.genenames.org/.
48. Wilming, L. G.; Gilbert, J. G.; Howe, K.; Trevanion, S.; Hubbard, T.; Harrow, J. L. The vertebrate genome annotation (Vega) database Nucleic Acids Res. 2008, 36, D753-760
49. The UniProt Consortium. Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res. 2012, 40, D71-D75.
50. Thomson-pharma-partnering. http://thomsonreuters.com/products-services/ science/science-products/a-z/thomson-pharma-partnering.
51. Thomson Reuters Integrity. http://thomsonreuters.com/products-services/ science/science-products/a-z/integrity.
52. ADIS R&D Insight. http://adisinsight.com/rd-insight/.
53. Citeline. http://www.citeline.com/.
54. Medline. http://www.nlm.nih.gov/bsd/pmresources.html.
55. Embase. http://www.embase.com/home.
56. Knowledge Discovery Platform. http://www.medintelsolutions.com.
57. ClinicalTrials.gov. http://clinicaltrials.gov.
58. TrialTrove. http://www.citeline.com/products/trialtrove/.
59. Solr. http://lucene.apache.org/solr.
60. Schuemie, M. J.; Jelier, R.; Kors, J. A. Peregrine: Lightweight Gene Name Normalization by Dictionary Lookup. Proceedings of the BioCreative II Workshop; BioCreative Organizing Committees, 2007.
61. Feldman, R.; Sanger, J. The Text Mining Handbook: Advanced Approaches in Analyzing Unstructured Data; Cambridge University Press: Cambridge, U.K., 2007.
62. Thompson, J. D.; Higgins, D. G.; Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice Nucleic Acids Res. 1994, 22, 4673-4680