Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens

E3 Ligand Binder

E3 ligase: VHL
E3 binder: Vh032 3-Fluoro-4-Hydroxyproline Analog
SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2[C@@H](F)[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

Ligand

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

Representative PROTAC (Active) name: 15a - status:Reviewed Edit

Calculated Values
MW: 1,020.65
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.54
TPSA: 211.49

SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2[C@@H](F)[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCNC(=O)C[C@@H]2N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc32)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 24
Cells: HeLa, MV4;11, A549
IC₅₀: = 249 nM
DC₅₀: < 3 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?: BRD2, BRD3

Comments: DC50 is 1-3nM

Contributed by: Daniel Zaidman

E3 Ligand Binder

E3 ligase: VHL
E3 binder: Vh032 3-Fluoro-4-Hydroxyproline Analog
SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2[C@H](F)[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

Ligand

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

PROTAC (Active) name: 15b - status:Reviewed Edit

Calculated Values
MW: 1,020.65
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.54
TPSA: 211.49

SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2[C@H](F)[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCNC(=O)C[C@@H]2N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc32)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 24
Cells: HeLa, MV4;11, A549
IC₅₀: = 603 nM
DC₅₀: < 30 nM
D_max: = 99 %
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?: BRD2, BRD3

Comments: DC50 is 10-30nM

Contributed by: Daniel Zaidman