1 research outputs found
Identification and Development of 2,3-Dihydropyrrolo[1,2‑<i>a</i>]quinazolin-5(1<i>H</i>)‑one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex
Bromodomain containing proteins PB1,
SMARCA4, and SMARCA2 are important
components of SWI/SNF chromatin remodeling complexes. We identified
bromodomain inhibitors that target these proteins and display unusual
binding modes involving water displacement from the KAc binding site.
The best compound binds the fifth bromodomain of PB1 with a <i>K</i><sub>D</sub> of 124 nM, SMARCA2B and SMARCA4 with <i>K</i><sub>D</sub> values of 262 and 417 nM, respectively, and
displays excellent selectivity over bromodomains other than PB1, SMARCA2,
and SMARCA4