Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: OTX015
IC₅₀: < 14 nM
SMILES: show

Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2

Representative PROTAC (Active) name: ARV-825 - status:Reviewed Edit

Calculated Values
MW: 923.45
Hbond donors: 3
Hbond acceptors: 15
cLogP: 5.77
TPSA: 204.67

SMILES: show

Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(OCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)cc1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 0.5,1,2,4,7,24
Cells: Namalwa, CA-46, Ramos
IC₅₀: < 90 nM
DC₅₀: < 1 nM
D_max: ~ 100 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No

Comments: tested also biological effects - proliferation and caspase activity on BL cells. IC50 of ligand is 14 nM (BD1), 3.5 nM (BD2). IC50 of PROTAC is 90 nM (BD1), 28 nM (BD2).

Contributed by: Adi Rogel