XY-06-007

XY-06-007 is a highly selective and potent "Bump & Hole" TAG Degrader (DC_50,6h = 10 nM, T_1/2 < 43.2 min). XY-06-007 comprises a cereblon (CRBN) E3 ligase ligand joined by a linker to a (+)-JQ1 (Cat. No. 4499) derivative (the "bump" bearer) that selectively binds the Brd4^{BD1 L94V} variant (the "hole"). In cell lines expressing a fusion of the target protein with the tag, Brd4^{BD1 L94V}, XY-06-007 drives formation of a ternary complex between CRBN and the tagged protein, leading to ubiquitination and subsequent proteasomal degradation of the entire protein. XY-06-007 is highly selective for Brd4^{BD1 L94V} over wild-type, and is broadly selective across the proteome. XY-06-007 can be combined with the dTAG approach to achieve simultaneous degrader-mediated depletion of their respective protein fusions. XY-06-007 is suitable for in vivo studies.

Sold under license from Dana-Farber Cancer Institute