David Kendall Jung
GlaxoSmithKline
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Publication
Featured researches published by David Kendall Jung.
Journal of Medicinal Chemistry | 2016
Peiling Chen; A. Chaikuad; Paul Bamborough; Marcus Bantscheff; C. Bountra; Chun Wa Chung; Oleg Fedorov; Paola Grandi; David Kendall Jung; Robert Lesniak; Matthew J Lindon; Susanne Müller; Martin Philpott; Rab K. Prinjha; Catherine Rogers; Carolyn Selenski; Cynthia Tallant; Thilo Werner; Timothy M. Willson; Stefan Knapp; David H. Drewry
Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology.
Archive | 2001
Michael John Alberti; Ian Robert Baldwin; Mui Cheung; Stuart Cockerill; Philip A. Harris; David Kendall Jung; Gregory Peckham; Michael Robert Peel; Jennifer Gabriel Badiang; Kirk L. Stevens; James Marvin Veal
Archive | 2005
David Kendall Drewry; David Kendall Jung; James Andrew Linn; Robert Neil Hunter; Dennis Lee; Robert A. Stavenger; Clark A. Sehon
Archive | 2003
Michael John Alberti; Stephen GlaxoSmithKline Pharm. Garland; David Kendall Jung; James Marvin Veal; Jason GlaxoSmithKline Witherington
Archive | 2005
Michael John Alberti; Stanley D. Chamberlain; Mui Cheung; Kristjan Gudmundsson; Philip A. Harris; Brian A. Johns; David Kendall Jung; Michael Robert Peel; Jennifer Badiang Stanford
Archive | 2006
David Kendall Jung; Michael John Alberti
Archive | 2004
David H. Drewry; Brian L. Evans; Krista B. Goodman; Darren Victor Steven Green; David Kendall Jung; Dennis Lee; Robert A. Stavenger; Sjoerd Nocolaas Wadman
Archive | 2005
Michael John GlaxoSmithKline Alberti; David Kendall Jung
Archive | 2005
Michael John GlaxoSmithKline Alberti; David Kendall Jung
Archive | 2001
F. Leslie Boyd; Stanley D. Chamberlain; Mui Cheung; Kristjan Gudmundsson; Philip A. Harris; Brian A. Johns; David Kendall Jung; Michael Robert Peel; Jo Connie Sexton; G. Jennifer Stanford