Kinetics for Drug Discovery: an industry-driven effort to target drug residence time

Doris A. Schuetz; Wilhelmus Egbertus Arnout de Witte; Yin Cheong Wong; Bernhard Knasmueller; Lars Richter; Daria B. Kokh; S. Kashif Sadiq; Reggie Bosma; Indira Nederpelt; Laura H Heitman; Elena Segala; Marta Amaral; Dong Guo; Dorothee Andres; Victoria Georgi; Leigh A. Stoddart; Steve Hill; Robert M. Cooke; C. de Graaf; Rob Leurs; Matthias Frech; Rebecca C. Wade; Elizabeth Cunera Maria de Lange; Adriaan P. IJzerman; Anke Müller-Fahrnow; Gerhard F. Ecker

doi:10.1016/j.drudis.2017.02.002

Kinetics for Drug Discovery: an industry-driven effort to target drug residence time

Doris A. Schuetz, Wilhelmus Egbertus Arnout de Witte, Yin Cheong Wong, Bernhard Knasmueller, Lars Richter, Daria B. Kokh, S. Kashif Sadiq, Reggie Bosma, Indira Nederpelt, Laura H Heitman, Elena Segala, Marta Amaral, Dong Guo, Dorothee Andres, Victoria Georgi, Leigh A. Stoddart, Steve Hill, Robert M. Cooke, C. de Graaf, Rob LeursMatthias Frech, Rebecca C. Wade, Elizabeth Cunera Maria de Lange, Adriaan P. IJzerman, Anke Müller-Fahrnow, Gerhard F. Ecker^*

^*Corresponding author for this work

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Abstract

A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target–ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public–private partnership.

Original language	English
Pages (from-to)	896-911
Number of pages	16
Journal	Drug Discovery Today
Volume	22
Issue number	6
Early online date	13 Apr 2017
DOIs	https://doi.org/10.1016/j.drudis.2017.02.002
Publication status	Published - Jun 2017

Funding

The authors are part of the K4DD consortium, which is supported by the Innovative Medicines Initiative Joint Undertaking (IMI JU) under grant agreement no 115366. The IMI JU is a project supported by the EU's Seventh Framework Programme (FP7/2007–2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA). DBK, SKS and RCW gratefully acknowledge the support of the Klaus Tschira Foundation.

Funders	Funder number
IMI JU	115366
Seventh Framework Programme
European Federation of Pharmaceutical Industries and Associations
Seventh Framework Programme
Klaus Tschira Stiftung
Innovative Medicines Initiative

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.drudis.2017.02.002

Kinetics for Drug Discovery an industry-driven effort to target drug residence timeFinal published version, 2.74 MBLicence: Article 25fa Dutch Copyright Act

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Schuetz, D. A., de Witte, W. E. A., Wong, Y. C., Knasmueller, B., Richter, L., Kokh, D. B., Sadiq, S. K., Bosma, R., Nederpelt, I., Heitman, L. H., Segala, E., Amaral, M., Guo, D., Andres, D., Georgi, V., Stoddart, L. A., Hill, S., Cooke, R. M., de Graaf, C., ... Ecker, G. F. (2017). Kinetics for Drug Discovery: an industry-driven effort to target drug residence time. Drug Discovery Today, 22(6), 896-911. https://doi.org/10.1016/j.drudis.2017.02.002

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abstract = "A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target–ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public–private partnership.",

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year = "2017",

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doi = "10.1016/j.drudis.2017.02.002",

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Schuetz, DA, de Witte, WEA, Wong, YC, Knasmueller, B, Richter, L, Kokh, DB, Sadiq, SK, Bosma, R, Nederpelt, I, Heitman, LH, Segala, E, Amaral, M, Guo, D, Andres, D, Georgi, V, Stoddart, LA, Hill, S, Cooke, RM, de Graaf, C, Leurs, R, Frech, M, Wade, RC, de Lange, ECM, IJzerman, AP, Müller-Fahrnow, A & Ecker, GF 2017, 'Kinetics for Drug Discovery: an industry-driven effort to target drug residence time', Drug Discovery Today, vol. 22, no. 6, pp. 896-911. https://doi.org/10.1016/j.drudis.2017.02.002

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AU - Schuetz, Doris A.

AU - de Witte, Wilhelmus Egbertus Arnout

AU - Wong, Yin Cheong

AU - Knasmueller, Bernhard

AU - Richter, Lars

AU - Kokh, Daria B.

AU - Sadiq, S. Kashif

AU - Bosma, Reggie

AU - Nederpelt, Indira

AU - Heitman, Laura H

AU - Segala, Elena

AU - Amaral, Marta

AU - Guo, Dong

AU - Andres, Dorothee

AU - Georgi, Victoria

AU - Stoddart, Leigh A.

AU - Hill, Steve

AU - Cooke, Robert M.

AU - de Graaf, C.

AU - Leurs, Rob

AU - Frech, Matthias

AU - Wade, Rebecca C.

AU - de Lange, Elizabeth Cunera Maria

AU - IJzerman, Adriaan P.

AU - Müller-Fahrnow, Anke

AU - Ecker, Gerhard F.

PY - 2017/6

Y1 - 2017/6

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Kinetics for Drug Discovery: an industry-driven effort to target drug residence time

Abstract

Funding

UN SDGs

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