High-throughput kinetics in drug discovery

Autor: Maria Filipa Pinto, Julija Sirina, Nicholas D Holliday, Claire L McWhirter

Publikováno v: SLAS Discovery, Vol 29, Iss 5, Pp 100170- (2024)

The importance of a drug's kinetic profile and interplay of structure-kinetic activity with PK/PD has long been appreciated in drug discovery. However, technical challenges have often limited detailed kinetic characterization of compounds to the latt

Externí odkaz: https://doaj.org/article/215d1b9e0e644570ab9c99b650955a7a

Role of G protein‐coupled receptor kinases (GRKs) in β2‐adrenoceptor‐mediated glucose uptake

Autor: Seungmin Ham, Saori Mukaida, Masaaki Sato, Peter Keov, Tore Bengtsson, Sebastian Furness, Nicholas D. Holliday, Bronwyn A. Evans, Roger J. Summers, Dana S. Hutchinson

Publikováno v: Pharmacology Research & Perspectives, Vol 12, Iss 1, Pp n/a-n/a (2024)

Abstract Truncation of the C‐terminal tail of the β2‐AR, transfection of βARKct or over‐expression of a kinase‐dead GRK mutant reduces isoprenaline‐stimulated glucose uptake, indicating that GRK is important for this response. We explored

Externí odkaz: https://doaj.org/article/8b05f72e8cfe40dba5549ad1377f554f

Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol

Autor: Reggie Bosma, Nicola C. Dijon, Yang Zheng, Hannes Schihada, Niels J. Hauwert, Shuang Shi, Marta Arimont, Rick Riemens, Hans Custers, Andrea van de Stolpe, Henry F. Vischer, Maikel Wijtmans, Nicholas D. Holliday, Diederik W.D. Kuster, Rob Leurs

Publikováno v: iScience, Vol 25, Iss 9, Pp 104882- (2022)

Summary: In this study, we synthesized and evaluated new photoswitchable ligands for the beta-adrenergic receptors β1-AR and β2-AR, applying an azologization strategy to the first-generation beta-blocker propranolol. The resulting compounds (Opto-p

Externí odkaz: https://doaj.org/article/febb6a52402644b994ea390ddeafdfc7

Discovery, Characterization, and Structure-Based Optimization of Small-Molecule In Vitro and In Vivo Probes for Human DNA Polymerase Theta

Autor: Martin L. Stockley, Amanda Ferdinand, Giovanni Benedetti, Peter Blencowe, Susan M. Boyd, Mat Calder, Mark D. Charles, Lucy V. Edwardes, Tennyson Ekwuru, Harry Finch, Alessandro Galbiati, Lerin Geo, Diego Grande, Vera Grinkevich, Nicholas D. Holliday, Wojciech W. Krajewski, Ellen MacDonald, Jayesh B. Majithiya, Hollie McCarron, Claire L. McWhirter, Viral Patel, Chris Pedder, Eeson Rajendra, Marco Ranzani, Laurent J. M. Rigoreau, Helen M. R. Robinson, Theresia Schaedler, Julija Sirina, Graeme C. M. Smith, Martin E. Swarbrick, Andrew P. Turnbull, Simon Willis, Robert A. Heald

Publikováno v: Journal of Medicinal Chemistry. 65:13879-13891

Human DNA polymerase theta (Polθ), which is essential for microhomology-mediated DNA double strand break repair, has been proposed as an attractive target for the treatment of BRCA deficient and other DNA repair pathway defective cancers. As previou

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a3234589eaa7f5350d23a2af196b12e
https://doi.org/10.1021/acs.jmedchem.2c01142

Optical control of the β2-adrenergic receptor with opto-prop-2:A cis-active azobenzene analog of propranolol

Autor: Reggie Bosma, Nicola C. Dijon, Yang Zheng, Hannes Schihada, Niels J. Hauwert, Shuang Shi, Marta Arimont, Rick Riemens, Hans Custers, Andrea van de Stolpe, Henry F. Vischer, Maikel Wijtmans, Nicholas D. Holliday, Diederik W.D. Kuster, Rob Leurs

Publikováno v: Bosma, R, Dijon, N C, Zheng, Y, Schihada, H, Hauwert, N J, Shi, S, Arimont, M, Riemens, R, Custers, H, van de Stolpe, A, Vischer, H F, Wijtmans, M, Holliday, N D, Kuster, D W D & Leurs, R 2022, ' Optical control of the β2-adrenergic receptor with opto-prop-2 : A cis-active azobenzene analog of propranolol ', iScience, vol. 25, no. 9, 104882 . https://doi.org/10.1016/j.isci.2022.104882
Bosma, R, Dijon, N C, Zheng, Y, Schihada, H, Hauwert, N J, Shi, S, Arimont, M, Riemens, R, Custers, H, van de Stolpe, A, Vischer, H F, Wijtmans, M, Holliday, N D, Kuster, D W D & Leurs, R 2022, ' Optical control of the β 2-adrenergic receptor with opto-prop-2 : A cis-active azobenzene analog of propranolol ', iScience, vol. 25, no. 9, 104882, pp. 1-19 . https://doi.org/10.1016/j.isci.2022.104882
iScience, 25(9):104882, 1-19. Elsevier
iScience, 25(9):104882. Elsevier Inc.

In this study, we synthesized and evaluated new photoswitchable ligands for the beta-adrenergic receptors β1-AR and β2-AR, applying an azologization strategy to the first-generation beta-blocker propranolol. The resulting compounds (Opto-prop-1, -2

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::570e6c0b6ad21c3fc99482159e6edb4d
https://research.vumc.nl/en/publications/04cdc2f5-c759-4d77-a27b-b1862fb11788