dWBP4-1 is a potent, highly selective, CRBN-dependent, phenotypically silent molecular glue degrader of spliceosome-associated scaffold protein WBP4 with DC50 of 3.4 nM in in MOLT-4 cells (Dmax=88%, 6h).
dWBP4-1 exhibits exceptional proteome-wide selectivity with negligible transcriptomic or alternative splicing perturbation.
WBP4-1 (100 nM) induced rapid and robust WBP4degradation as early as 30 min post-treatment in MOLT-4 cells via immunoblot analysis.
dWBP4-1 selectively degraded WBP4 without affecting other canonical IMiD targetsor spliceosomal components such as SNRPB2, WBP11, SF3B1-4, and SNRNP200.
dWBP4-1 efficiently mediates the proximity of CRBN and WBP4 with EC50 of 224 nM.
WW domain-binding protein 4 (WBP4), originally identifiedas formin-binding protein 21 (FBP21), is a 376-residue proteincharacterized by two tandem WW domains and a zinc-fingermotif, is a critical component of the RNA splicingmachinery.