Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to non-bromodomain and extra terminal domain (non-BET) bromodomains through displacement of a normally conserved network of four water molecules. Starting from an initial hit molecule, we report its divergent optimization toward the
ATPase
family AAA domain containing 2 (ATAD2) and
cat eye syndrome chromosome region, candidate 2
(
CECR2
) domains. This work concludes with the identification of
(
R
)-55
(GSK232), a highly selective, cellularly penetrant
CECR2
inhibitor with excellent physicochemical properties.
...
PMID:Optimization of Potent ATAD2 and CECR2 Bromodomain Inhibitors with an Atypical Binding Mode. 3232 Dec 40
