PROTACpedia
Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481. PMID:28339196 DOI:10.1021/acs.jmedchem.6b01816
Target: BRD3 Bromodomain-containing protein 3 Q15059 Homo sapiens
E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show
Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 798.91
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.13
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 nM
Dmax: = 100 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 770.85
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.35
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 10 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 784.88
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.74
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 812.93
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.52
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 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
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 871.91
Hbond donors: 5
Hbond acceptors: 15
cLogP: 4.34
TPSA: 257.66

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 10 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
Comments: Direct degration studies in this paper only conducted for first and final compounds; during the med chem campaign cell viability was used as the read out. Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD. DC50 is between 3nM-10nM.
Contributed by: Ronen Gabizon
Target: BRD2 Bromodomain-containing protein 2 P25440 Homo sapiens
E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show
Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 798.91
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.13
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 nM
Dmax: = 100 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 770.85
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.35
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 10 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 812.93
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.52
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 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
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 784.88
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.74
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 871.91
Hbond donors: 5
Hbond acceptors: 15
cLogP: 4.34
TPSA: 257.66

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 10 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
Comments: Direct degration studies in this paper only conducted for first and final compounds; during the med chem campaign cell viability was used as the read out. Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD. DC50 is between 3nM-10nM.
Contributed by: Ronen Gabizon
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show
Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 798.91
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.13
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 nM
Dmax: = 100 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 770.85
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.35
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 10 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 812.93
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.52
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 1 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
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
Calculated Values
MW: 784.88
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.74
TPSA: 202.26

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: ~ 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
Off-targets reported?: No
Comments: Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: HJB97
IC50: < 7 nM
SMILES: show
CCn1nc(C2CC2)cc1Nc1ncnc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Calculated Values
MW: 871.91
Hbond donors: 5
Hbond acceptors: 15
cLogP: 4.34
TPSA: 257.66

SMILES: show
CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12

Linker type: Alkane
Incubation time (hours): 3
Cells: RS4;11, MOLM-13
DC50: < 10 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
Comments: Direct degration studies in this paper only conducted for first and final compounds; during the med chem campaign cell viability was used as the read out. Complex structure with the ligand was modeled based on 4Z93. IC50 of the ligand is between 2nM and 7nM, depending on which BRD. DC50 is between 3nM-10nM.
Contributed by: Ronen Gabizon