Abstract
There are great opportunities for innovation in the drug discovery process, particularly in the lead development phase. The traditional “design-synthesize-screen” cycle has seen little innovation as a whole despite major advances at each stage, including automated purification and synthesis as well as high throughput biological screening. It could be argued that the hit-to-lead and lead optimization processes remain slow and modular with inefficient flow of information, resulting in a loss of time and money. New flow technologies may provide a promising foundation for developing a continuous integrated small molecule optimization platform that would greatly enhance hit-to-lead and lead optimization programs. Herein, we discuss major developments in integrating synthesis, purification, screening, and machine learning into a single continuous-flow platform and provide some insight into future directions of this field.
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Dittrich, P. S.; Manz, A. Nat. Rev. Drug. Disc. 2006, 5, 210.
Watts, P. Anal. Bioanal. Chem. 2005, 382, 865.
Belder, D. Anal. Bioanal. Chem. 2006, 385, 416.
Wong Hawkes, S. Y. F.; Chapela, M. J. V.; Montembault, M. QSAR Comb. Sci. 2005, 24.
Malet-Santz, L.; Susanne, F. J. Med. Chem. 2012, 55, 4062.
Whitesides, G. Nature, 2006, 442, 368.
Yeo, L. Y.; Chang, H.-C.; Chan, P. P. Y.; Friend, J. R. Small 2011, 7, 12.
Duncombe, T. A.; Tentori, A. M.; Herr, A. E. Nat. Rev. Drug Disc. 2015, 16, 554.
Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. Chem. Rev. 2017, 117, 11796.
Kockmann, N.; Roberge, D. M. Chem. Eng. Technol. 2009, 32, 1682–1694.
Movsisyan, M.; Delbeke, E. I. P.; Berton, J. K. E. T.; Battilocchio, C.; Ley, S. V.; Stevens, C. V. Chem. Soc. Rev 2016, 45, 4892–4928.
Kockmann, N.; Thenee, P.; Fleischer-Trebes, C.; Laudadio, G.; Noel, T. React. Chem. Eng. 2017, 2, 258.
Gutmann, B.; Cantillo, D.; Kappe, C. O. Angew. Chem. Int. Ed. 2015, 54, 6688.
Porta, R.; Benaglia, M.; Puglisi, A. Org. Proc. Res. Dev. 2016, 20, 2.
Hochlowski, J. E.; Searle, P. A.; Tu, N. P.; Pan, J. Y.; Spanton, S. G.; Djuric, S. W. J.Flow. Chem. 2011, 2, 56.
Sutherland, J. D.; Tu, N. P.; Nemcek, T. A.; Searle, P. A.; Hochlowski, J. E.; Djuric, S. W.; Pan, J. Y. J. Lab. Aut. 2014, 19, 176.
Baranczak, A.; Tu, N. P.; Marjanovic, J.; Searle, P. A.; Vasudevan, A.; Djuric, S. W. ACS Med. Chem. Lett. 2017, 8, 461.
Hwang, Y.-J.; Coley, C. W.; Abolhasani, M.; Marzinzik, A. L.; Koch, G.; Spanka, C.; Lehmann, H.; Jensen, K. F. Chem. Commun. 2017, 53, 6649.
Weibel, D. B.; Whitesides, G. M. Curr Op. Chem. Biol. 2006, 10, 584.
Eribol, P.; Uguz, A. K., Ulgen, K. O. Biomicrofluidics, 2016, 10, 1.
Heus, F.; Giera, M.; de Kloe, G. E.; van Iperen, D.; Buijs, J.; Nahar, T. T.; Smit, A. B.; Lingeman, H.; de Esch, I. J. P.; Niessen, W. M. A.; Irth, H.; Kool, J. Anal. Bioanal. Chem. 2010, 398, 3023.
Hirata, J.; Ariese, F.; Gooijer, C.; Irth, H. Anal. Chim. Acta. 2003, 478, 1.
Hirata, J.; Chung, L. P.; Ariese, F.; Irth, H.; Gooijer, C. J. Chrom. A. 2005, 1081, 140.
Werner, M.; Kuratli, C.; Martin, R. E.; Hochstrasser, R.; Wechsler, D.; Enderle, T.; Alanine, A. I.; Vogel, H. Angew. Chem. Int. Ed. 2014, 53, 1704.
Ramjee, M. K.; Patel, S. Anal. Biochem. 2017, 528, 38.
Guetzoyan, L.; Nikbin, N.; Baxendale, I. R.; Ley, S. V. Chem. Sci. 2013, 4, 764.
Guetzoyan, L.; Ingham, R. J.; Nikbin, N.; Rossignol, J.; Wolling, M.; Baumert, M.; Burgess-Brown, N. A.; Strain-Damerell, C. M.; Shrestha, L.; Brennan, P. E.; Federov, O.; Knapp, S.; Ley, S. V. Med. Chem. Commun. 2014, 5, 540.
Murray, J. B.; Roughley, S. D.; Matassova, N.; Brough, P. A. J. Med. Chem. 2014, 57, 2845.
Desai, B.; Dixon, K.; Farrant, E.; Feng, Q.; Gibson, K. R.; van Hoom, W. P.; Mills, J.; Morgan, T.; Parry, D. M.; Ramjee, M. K.; Selway, C. N.; Tarver, G. J.; Whitlock, G.; Wright, A. G. J. Med. Chem. 2013, 56, 3033.
Czechtizky, W.; Dedio, J.; Desai, B.; Dixon, K.; Farrant, E.; Feng, Q.; Morgan, T.; Parry, D. M.; Ramjee, M. K.; Selway, C. N.; Schmidt, T.; Tarver, G. J.; Wright, A. G. ACS Med. Chem. Lett. 2013, 4, 768.
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Fleming, G.S., Beeler, A.B. Integrated Drug Discovery in Continuous Flow. J Flow Chem 7, 124–128 (2017). https://doi.org/10.1556/1846.2017.00027
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DOI: https://doi.org/10.1556/1846.2017.00027