Target: BRD4 Bromodomain-containing protein 4 O60885 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: compound 6
IC₅₀: = 46.4 nM
EC₅₀ (cells): = 3.26 μM
SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)NC(N3C)=O)=C2

Representative PROTAC (Active) name: Compound 21 - status:Reviewed Edit

Calculated Values
MW: 757.76
Hbond donors: 2
Hbond acceptors: 12
cLogP: 3.73
TPSA: 202.17

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(COCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7=O)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
Cells: THP-1
IC₅₀: = 41.8 nM
EC₅₀ (cells): = 0.81 μM
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: No

Comments: IC50 of PROTAC with error of ± 7.8 nM

Contributed by: Shimrit Azulay, Daniel Zaidman

PROTAC (Active) name: Compound 24 - status:Reviewed Edit

Calculated Values
MW: 875.90
Hbond donors: 2
Hbond acceptors: 15
cLogP: 3.73
TPSA: 229.86

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCOCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7=O)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
IC₅₀: = 173.4 nM
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

Comments: IC50 of PROTAC with error of ± 23.2 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 23 - status:Reviewed Edit

Calculated Values
MW: 845.87
Hbond donors: 2
Hbond acceptors: 14
cLogP: 3.76
TPSA: 220.63

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7=O)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
Cells: THP-1
IC₅₀: = 68.5 nM
EC₅₀ (cells): = 1.75 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?: No

Comments: IC50 of PROTAC with error of ± 8.5 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 22 - status:Reviewed Edit

Calculated Values
MW: 815.84
Hbond donors: 2
Hbond acceptors: 13
cLogP: 3.78
TPSA: 211.40

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7=O)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
Cells: THP-1
IC₅₀: = 67.7 nM
EC₅₀ (cells): = 1.66 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?: No

Comments: IC50 of PROTAC with error of ± 9.0 nM

Contributed by: Shimrit Azulay

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show

Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: compound 6
IC₅₀: = 46.4 nM
EC₅₀ (cells): = 3.26 μM
SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)NC(N3C)=O)=C2

PROTAC (Active) name: Compound 20 - status:Reviewed Edit

Calculated Values
MW: 861.91
Hbond donors: 2
Hbond acceptors: 14
cLogP: 4.09
TPSA: 212.79

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCOCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
IC₅₀: = 22.6 nM
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

Comments: IC50 of PROTAC with error of ± 3.7 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 11 - status:Reviewed Edit

Calculated Values
MW: 745.84
Hbond donors: 3
Hbond acceptors: 8
cLogP: 5.00
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 99.1 nM
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

Comments: IC50 of PROTAC with error of ± 8.7 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 12 - status:Reviewed Edit

Calculated Values
MW: 759.86
Hbond donors: 3
Hbond acceptors: 8
cLogP: 5.39
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 80.6 nM
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

Comments: IC50 of PROTAC with error of ± 6.5 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 16 - status:Reviewed Edit

Calculated Values
MW: 702.81
Hbond donors: 2
Hbond acceptors: 7
cLogP: 6.27
TPSA: 145.16

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CCCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 118.2 nM
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

Comments: IC50 of PROTAC with error of ± 12.6 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 19 - status:Reviewed Edit

Calculated Values
MW: 831.89
Hbond donors: 2
Hbond acceptors: 13
cLogP: 4.12
TPSA: 203.56

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
IC₅₀: = 22.1 nM
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

Comments: IC50 of PROTAC with error of ± 2.9 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 17 - status:Reviewed Edit

Calculated Values
MW: 743.78
Hbond donors: 2
Hbond acceptors: 11
cLogP: 4.09
TPSA: 185.10

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(COCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
Cells: THP-1
IC₅₀: = 14.2 nM
EC₅₀ (cells): = 1.83 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?: No

Comments: IC50 of PROTAC with error of ± 1.6 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 14 - status:Reviewed Edit

Calculated Values
MW: 674.76
Hbond donors: 2
Hbond acceptors: 7
cLogP: 5.49
TPSA: 145.16

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 143.7 nM
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

Comments: IC50 of PROTAC with error of ± 13.6 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 8 - status:Reviewed Edit

Calculated Values
MW: 703.76
Hbond donors: 3
Hbond acceptors: 8
cLogP: 3.83
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 132.2 nM
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

Comments: IC50 of PROTAC with error of ± 13.8 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 13 - status:Reviewed Edit

Calculated Values
MW: 773.89
Hbond donors: 3
Hbond acceptors: 8
cLogP: 5.78
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCCCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 68.3 nM
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

Comments: IC50 of PROTAC with error of ± 7.1 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 18 - status:Reviewed Edit

Calculated Values
MW: 801.86
Hbond donors: 2
Hbond acceptors: 12
cLogP: 4.14
TPSA: 194.33

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC5=CN(CCOCCOCC(NC6=C7C(C(N(C8CCC(NC8=O)=O)C7)=O)=CC=C6)=O)N=N5)C(N3C)=O)=C2

Linker type: PEG
IC₅₀: = 15.4 nM
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

Comments: IC50 of PROTAC with error of ± 2.3 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 9 - status:Reviewed Edit

Calculated Values
MW: 717.78
Hbond donors: 3
Hbond acceptors: 8
cLogP: 4.22
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 138.4 nM
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

Comments: IC50 of PROTAC with error of ± 15.4 nM

Contributed by: Shimrit Azulay

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

Calculated Values
MW: 688.79
Hbond donors: 2
Hbond acceptors: 7
cLogP: 5.88
TPSA: 145.16

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 135.1 nM
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

Comments: IC50 of PROTAC with error of ± 14.0 nM

Contributed by: Shimrit Azulay

PROTAC (Active) name: Compound 10 - status:Reviewed Edit

Calculated Values
MW: 731.81
Hbond donors: 3
Hbond acceptors: 8
cLogP: 4.61
TPSA: 174.26

SMILES: show

CC1=NOC(C)=C1C2=CC=C3C(C(C4=CC=CC=C4)N(CC(NCCCCC(NC5=C6C(C(N(C7CCC(NC7=O)=O)C6)=O)=CC=C5)=O)=O)C(N3C)=O)=C2

Linker type: Alkane
IC₅₀: = 133.6 nM
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

Comments: IC50 of PROTAC with error of ± 14.2 nM

Contributed by: Shimrit Azulay