Targeting bromodomains: epigenetic readers of lysine acetylation.

Nature reviews. Drug discovery (2014-04-23)
Panagis Filippakopoulos, Stefan Knapp
ABSTRACT

Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of which have a key role in the acetylation-dependent assembly of transcriptional regulator complexes. These complexes can then initiate transcriptional programmes that result in phenotypic changes. The recent discovery of potent and highly specific inhibitors for the BET (bromodomain and extra-terminal) family of bromodomains has stimulated intensive research activity in diverse therapeutic areas, particularly in oncology, where BET proteins regulate the expression of key oncogenes and anti-apoptotic proteins. In addition, targeting BET bromodomains could hold potential for the treatment of inflammation and viral infection. Here, we highlight recent progress in the development of bromodomain inhibitors, and their potential applications in drug discovery.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Lysine, ≥98% (TLC)
Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Lysine, crystallized, ≥98.0% (NT)
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Supelco
L-Lysine, analytical standard
Supelco
L-Lysine monohydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Lysine monohydrochloride, BioUltra, ≥99.5% (AT)
Sigma-Aldrich
L-Lysine acetate salt, ≥98% (HPLC)
Supelco
L-Lysine Acetate, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Lysine monohydrochloride, certified reference material, TraceCERT®
Lysine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(-)-JQ1, ≥95% (HPLC)
Lysine acetate, European Pharmacopoeia (EP) Reference Standard