PROTACpedia
A novel cereblon modulator for targeted protein degradation. Eur J Med Chem. 2019 Mar 15;166:65-74. PMID:30684871 DOI:10.1016/j.ejmech.2019.01.023
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: Cereblon
E3 binder: Td-106
SMILES: show
Nc1cccc2nnn(C3CCC(=O)NC3=O)c(=O)c12

 Ligand Name: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2

Calculated Values
MW: 879.40
Hbond donors: 3
Hbond acceptors: 16
cLogP: 5.44
TPSA: 205.84

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1cccc(OCCOCCOCCNc3cccc4nnn(C5CCC(=O)NC5=O)c(=O)c34)c1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 24
Cells: 22Rv1
DC50: = 0.32 nM
Dmax: = 100 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 879.40
Hbond donors: 3
Hbond acceptors: 16
cLogP: 5.44
TPSA: 205.84

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(OCCOCCOCCNc3cccc4nnn(C5CCC(=O)NC5=O)c(=O)c34)cc1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 24
Cells: 22Rv1
DC50: = 3.3 nM
Dmax: = 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
Contributed by: Daniel Zaidman
Calculated Values
MW: 783.36
Hbond donors: 3
Hbond acceptors: 13
cLogP: 5.84
TPSA: 178.15

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCCCCCCCNc1cccc3nnn(C4CCC(=O)NC4=O)c(=O)c13)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 24
Cells: 22Rv1
Dmax: = 63 %
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
Contributed by: Daniel Zaidman
Calculated Values
MW: 787.30
Hbond donors: 3
Hbond acceptors: 15
cLogP: 3.53
TPSA: 196.61

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCOCCOCCNc1cccc3nnn(C4CCC(=O)NC4=O)c(=O)c13)c1nnc(C)n1-2

Linker type: Alkane
Incubation time (hours): 24
Cells: 22Rv1
Dmax: = 36 %
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
Contributed by: Daniel Zaidman