PLX3618

PLX3618 is a monovalent direct degrader of bromodomain-containing protein 4 (BRD4). It binds to both bromodomain 1 (BD1) and BD2 of BRD4 and mediates its degradation via recruitment of the E3 ubiquitin ligase DDB1- and CUL4-associated factor 11 (DCAF11) with a half-maximal degradation concentration (DC50) value of 12.2 nM. PLX3618 inhibits the proliferation of a variety of hematopoietic cancer cells and induces apoptosis in MV4-11 acute myeloid leukemia (AML) cells. It induces tumor regression and intratumoral BRD4 degradation in an MV4-11 mouse xenograft model when administered at a dose of 5 mg/kg. SMILES: CC1=C(C)C(C(C2=CC=C(C3=CC(NC(C4=C5N(C=CC=N5)N=C4)=O)=CC=C3)C=C2)=N[C@H](C6=NN=C(N67)C)CC(N)=O)=C7S1. InChi Code: InChI=1S/C32H27N9O2S/c1-17-18(2)44-32-27(17)28(37-25(15-26(33)42)30-39-38-19(3)41(30)32)21-10-8-20(9-11-21)22-6-4-7-23(14-22)36-31(43)24-16-35-40-13-5-12-34-29(24)40/h4-14,16,25H,15H2,1-3H3,(H2,33,42)(H,36,43)/t25-/m0/s1. InChi Key: KGEBVZGNEUJHIO-VWLOTQADSA-N