Target: PLK1 Serine/threonine-protein kinase PLK1 P53350 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: BI2536
Ligand PDB Id: R78
PDB with Ligand: 4O74
IC₅₀: = 25 nM
SMILES: show

CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccccc3OC)nc2N1C1CCCC1

Representative PROTAC (Active) name: HBL-4 - status:Reviewed Edit

Calculated Values
MW: 811.90
Hbond donors: 4
Hbond acceptors: 14
cLogP: 3.01
TPSA: 213.73

SMILES: show

CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NCCOCCOCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)cc3OC)nc2N1C1CCCC1

Linker type: PEG
Incubation time (hours): 24
Cells: MV4-11, MOLM-13, KG1
DC₅₀: < 5 nM
D_max: ~ 100 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No

Comments: They show "dual" degradation but don't do any test that the dual degradation actually made any difference. They make it sound novel but of course we can call our PROTACs "dual" degraders if you can the off-targets "targets". EC50 of ligand is in measured in MV4-11 cell line. EC50 of PROTAC is between 4.5nM-6.94nM (depended on the cell line).

Contributed by: Ronen Gabizon

Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens