Figure 2. Design and screening of a synthetically enable, ‘poised’ fragment library (DSPL) identified two hits for the atypical, second bromodomain of PHIP.

(A) All fragments in DSPL contain drug-like cores that can rapidly be constructed from robust reactions with populous building blocks. PHIP hits substructures highlighted. (B) Crystal structures of hits 1 (lavender) and 2 (peach) in the second bromodomain of PHIP. (C) Synthesis of analogues of hits 1 and 2 gave compounds 3 and 4 with measurable IC50’s.