JQ1-JX5 is a DCAF16-based BRD4 PROTAC degrader. JQ1-JX5 covalently modifies Cys58 of DCAF16, promotes ternary complex formation with BRD4, enables BRD4 ubiquitination and proteasomal degradation. JQ1-JX5 induces time-dependent degradation of BRD4 long and short isoforms in AGS cells with DC50 of 43.97 and 16.77 nM. JQ1-JX5 can be used for the research of cancer, such as acute myeloid leukemia [1]. (Pink: BRD4 ligand; Blue: DCAF16 ligand; Black: linker).
In Vitro, JQ1-JX5 (1.0 μM; 3-36 h) induces time-dependent degradation of BRD4 long and short isoforms in AGS cells with DC50 of 43.97 and 16.77 nM, and ~90% loss of both isoforms achieved by 24 hours[1]. JQ1-JX5 (0.01-5 μM; 12 h) induces degradation of BRD4 long and short isoforms in AGS, MDA-MB-453, AsPC1, MV-4-11, MDA-MB-231, and HEK293T cells[1]. JQ1-JX5 inhibits AGS cells proliferation with an IC50 of 0.4993 μM[1]. JQ1-JX5 mediates the degradation of BRD4 by covalent recruitment of DCAF16[1].
References:
[1]. Zhang J, et al. New Reversible Covalent Warheads: Cyanobenzothiazoles Recruiting DCAF16 for Targeted Protein Degradation. J Med Chem. 2026;69(9):11620-11637.
In Vitro, JQ1-JX5 (1.0 μM; 3-36 h) induces time-dependent degradation of BRD4 long and short isoforms in AGS cells with DC50 of 43.97 and 16.77 nM, and ~90% loss of both isoforms achieved by 24 hours[1]. JQ1-JX5 (0.01-5 μM; 12 h) induces degradation of BRD4 long and short isoforms in AGS, MDA-MB-453, AsPC1, MV-4-11, MDA-MB-231, and HEK293T cells[1]. JQ1-JX5 inhibits AGS cells proliferation with an IC50 of 0.4993 μM[1]. JQ1-JX5 mediates the degradation of BRD4 by covalent recruitment of DCAF16[1].
References:
[1]. Zhang J, et al. New Reversible Covalent Warheads: Cyanobenzothiazoles Recruiting DCAF16 for Targeted Protein Degradation. J Med Chem. 2026;69(9):11620-11637.