HL435 is a potent, alkenyl oxindole-based heterobifunctional BRD4 degrader PROTAC with DC50 values of 11.9 and 21.9 nM in MDA-MB-231 and MCF-7 cells, respectively.
HL435 is demonstrated to efficiently degrade BRD4 in a concentration-dependent manner in multiple cell lines, the Dmax all >95%.
CRL4 DCAF11 complex is potentially responsible for HL435-induced proteasomal degradation activity.
HL435 recruits CRL4DCAF11 complex to induce proteasomal degradation of BRD4.
HL435 potently inhibits proliferation and induces apoptosis of tumor cells in vitro (22RV1 prostate cancer cell, IC50 of 8.6 nM), significantly superior to JQ1 (IC50 = 157 nM).
HL435 not only exhibits excellent antiproliferative capacity against multiple tumor cell lines but also effectively arrests the cell cycle and induces apoptosis in breast cancer cells (MCF-7, MDA-MB-231, IC50=0.38 and 0.21 uM, respectively).
HL435 (20 mg/kg, daily, i.p.) exhibits potent antitumor ability in mouse xenograft tumor model of MDA-MB-231 xenograft.