PROTACpedia
A "Click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation. J Med Chem. 2018 Jan 25;61(2):453-461. PMID:28378579 DOI:10.1021/acs.jmedchem.6b01781
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 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: 957.47
Hbond donors: 2
Hbond acceptors: 18
cLogP: 3.64
TPSA: 232.58

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCn1cc(COCCOCCOCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.20 μM
Dmax: > 90 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: No
Contributed by: Ella Livnah
Calculated Values
MW: 781.25
Hbond donors: 2
Hbond acceptors: 14
cLogP: 3.58
TPSA: 195.66

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCn1cc(COc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.49 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 913.41
Hbond donors: 2
Hbond acceptors: 17
cLogP: 3.63
TPSA: 223.35

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCn1cc(COCCOCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.45 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 869.36
Hbond donors: 2
Hbond acceptors: 16
cLogP: 3.61
TPSA: 214.12

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCn1cc(COCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: > 5 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 825.31
Hbond donors: 2
Hbond acceptors: 15
cLogP: 3.59
TPSA: 204.89

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCn1cc(COCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn1)c1nnc(C)n1-2

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: > 5 μM
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?: No
Contributed by: Ella Livnah
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: 995.63
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.36
TPSA: 223.74

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCc2cn(CCNC(=O)C[C@@H]3N=C(c4ccc(Cl)cc4)c4c(sc(C)c4C)-n4c(C)nnc43)nn2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.059 μM
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: No
Contributed by: Ella Livnah
Calculated Values
MW: 1,039.69
Hbond donors: 4
Hbond acceptors: 17
cLogP: 5.37
TPSA: 232.97

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCc2cn(CCNC(=O)C[C@@H]3N=C(c4ccc(Cl)cc4)c4c(sc(C)c4C)-n4c(C)nnc43)nn2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.083 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 1,083.74
Hbond donors: 4
Hbond acceptors: 18
cLogP: 5.39
TPSA: 242.20

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCc2cn(CCNC(=O)C[C@@H]3N=C(c4ccc(Cl)cc4)c4c(sc(C)c4C)-n4c(C)nnc43)nn2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.24 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 1,171.84
Hbond donors: 4
Hbond acceptors: 20
cLogP: 5.42
TPSA: 260.66

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOCCOCc2cn(CCNC(=O)C[C@@H]3N=C(c4ccc(Cl)cc4)c4c(sc(C)c4C)-n4c(C)nnc43)nn2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.63 μM
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?: No
Contributed by: Ella Livnah
Calculated Values
MW: 1,127.79
Hbond donors: 4
Hbond acceptors: 19
cLogP: 5.40
TPSA: 251.43

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOCc2cn(CCNC(=O)C[C@@H]3N=C(c4ccc(Cl)cc4)c4c(sc(C)c4C)-n4c(C)nnc43)nn2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 4
Cells: H661
DC50: = 0.46 μM
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?: No
Contributed by: Ella Livnah