PROTACpedia
Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol. 2017 Mar 13. PMID:28288108 DOI:10.1038/nchembio.2329
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: VHL
E3 binder: Vh032
SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

 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: 972.70
Hbond donors: 4
Hbond acceptors: 13
cLogP: 7.59
TPSA: 183.80

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: Alkane
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 960.65
Hbond donors: 4
Hbond acceptors: 14
cLogP: 6.05
TPSA: 193.03

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCOCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: PEG
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,004.70
Hbond donors: 4
Hbond acceptors: 15
cLogP: 6.07
TPSA: 202.26

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCOCCOCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: PEG
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,002.66
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.60
TPSA: 211.49

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[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
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 958.61
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.58
TPSA: 202.26

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCNC(=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
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,046.71
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.61
TPSA: 220.72

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOCCNC(=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
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 988.70
Hbond donors: 4
Hbond acceptors: 14
cLogP: 6.83
TPSA: 193.03

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCOCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,149.84
Hbond donors: 5
Hbond acceptors: 16
cLogP: 6.32
TPSA: 240.59

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)[C@@H](Cc2ccccc2)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
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 944.65
Hbond donors: 4
Hbond acceptors: 13
cLogP: 6.81
TPSA: 183.80

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: Alkane
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman
Calculated Values
MW: 988.70
Hbond donors: 4
Hbond acceptors: 14
cLogP: 6.83
TPSA: 193.03

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCOCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: Hela
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3
Contributed by: Daniel Zaidman