PROTACpedia
Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL. Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10. PMID:26593377 DOI:10.1002/anie.201507634
Target: ABL1 Tyrosine-protein kinase ABL1 P00519 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Bosutinib
Ligand PDB Id: DB8
PDB with Ligand: 3UE4
IC50: = 0.063 nM
SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c(Cl)cc1Cl

Calculated Values
MW: 1,074.07
Hbond donors: 3
Hbond acceptors: 16
cLogP: 7.77
TPSA: 223.22

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCCOCCCCCC(=O)Nc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.91 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,072.10
Hbond donors: 3
Hbond acceptors: 15
cLogP: 8.92
TPSA: 213.99

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCCCCOCCCCCC(=O)Nc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 2.8 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,150.12
Hbond donors: 3
Hbond acceptors: 19
cLogP: 6.26
TPSA: 250.91

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)Nc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.38 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 973.91
Hbond donors: 3
Hbond acceptors: 15
cLogP: 6.19
TPSA: 213.99

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCC(=O)Nc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.28 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Dasatinib
Ligand PDB Id: 1N1
PDB with Ligand: 2GQG
IC50: = 0.030 nM
SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCO)CC2)n1

Calculated Values
MW: 901.45
Hbond donors: 4
Hbond acceptors: 15
cLogP: 4.95
TPSA: 217.39

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCC(=O)Nc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.28 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,001.61
Hbond donors: 4
Hbond acceptors: 16
cLogP: 6.53
TPSA: 226.62

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCCOCCCCCC(=O)Nc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.60 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,077.66
Hbond donors: 4
Hbond acceptors: 19
cLogP: 5.02
TPSA: 254.31

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)Nc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.26 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 999.64
Hbond donors: 4
Hbond acceptors: 15
cLogP: 7.69
TPSA: 217.39

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCCCCOCCCCCC(=O)Nc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 1.3 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: c-ABL and BCR-ABL degredation
Contributed by: Efrat Resnick
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: Dasatinib
Ligand PDB Id: 1N1
PDB with Ligand: 2GQG
IC50: = 0.030 nM
SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCO)CC2)n1

Calculated Values
MW: 1,156.96
Hbond donors: 5
Hbond acceptors: 16
cLogP: 9.89
TPSA: 216.37

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCCCCOCCCCCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCc3ccc(-c4scnc4C)cc3)C(C)(C)C)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 2.6 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
Off-targets reported?: No
Comments: c-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,234.98
Hbond donors: 5
Hbond acceptors: 20
cLogP: 7.22
TPSA: 253.29

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCc3ccc(-c4scnc4C)cc3)C(C)(C)C)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.28 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: c-ABL degredation
Contributed by: Efrat Resnick
Calculated Values
MW: 1,058.77
Hbond donors: 5
Hbond acceptors: 16
cLogP: 7.16
TPSA: 216.37

SMILES: show
Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCc3ccc(-c4scnc4C)cc3)C(C)(C)C)CC2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.36 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: c-ABL degredation
Contributed by: Efrat Resnick
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: Bosutinib
Ligand PDB Id: DB8
PDB with Ligand: 3UE4
IC50: = 0.063 nM
SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c(Cl)cc1Cl

Calculated Values
MW: 1,131.24
Hbond donors: 4
Hbond acceptors: 16
cLogP: 8.40
TPSA: 212.97

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)NCc5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 1.3 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
Contributed by: Efrat Resnick
Calculated Values
MW: 1,229.43
Hbond donors: 4
Hbond acceptors: 16
cLogP: 11.13
TPSA: 212.97

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCCCCOCCCCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)NCc5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 4.6 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
Off-targets reported?: No
Contributed by: Efrat Resnick
Calculated Values
MW: 1,307.45
Hbond donors: 4
Hbond acceptors: 20
cLogP: 8.46
TPSA: 249.89

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)NCc5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 0.57 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
Contributed by: Efrat Resnick
Calculated Values
MW: 1,231.40
Hbond donors: 4
Hbond acceptors: 17
cLogP: 9.97
TPSA: 222.20

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCCCCCOCCOCCOCCCCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)NCc5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 1.4 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
Off-targets reported?: No
Contributed by: Efrat Resnick
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: imatinib
Ligand PDB Id: STI
PDB with Ligand: 2HYY
IC50: = 0.86 nM
SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Calculated Values
MW: 1,192.59
Hbond donors: 5
Hbond acceptors: 15
cLogP: 10.53
TPSA: 216.37

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCCCCOCCCCCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 19 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
Contributed by: Efrat Resnick
Calculated Values
MW: 1,094.40
Hbond donors: 5
Hbond acceptors: 15
cLogP: 7.80
TPSA: 216.37

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 5.8 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
Contributed by: Efrat Resnick
Calculated Values
MW: 1,270.61
Hbond donors: 5
Hbond acceptors: 19
cLogP: 7.86
TPSA: 253.29

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 1.7 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
Off-targets reported?: No
Contributed by: Efrat Resnick
Calculated Values
MW: 1,194.56
Hbond donors: 5
Hbond acceptors: 16
cLogP: 9.37
TPSA: 225.60

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCCOCCCCCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 4.3 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
Contributed by: Efrat Resnick
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: imatinib
Ligand PDB Id: STI
PDB with Ligand: 2HYY
IC50: = 0.86 nM
SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Calculated Values
MW: 1,113.28
Hbond donors: 4
Hbond acceptors: 18
cLogP: 5.66
TPSA: 254.31

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCCOCCOCCOCCOCC(=O)Nc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 3.0 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
Contributed by: Efrat Resnick
Calculated Values
MW: 1,037.23
Hbond donors: 4
Hbond acceptors: 15
cLogP: 7.17
TPSA: 226.62

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCCOCCCCCC(=O)Nc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 6.2 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
Off-targets reported?: No
Contributed by: Efrat Resnick
Calculated Values
MW: 937.07
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.59
TPSA: 217.39

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCOCC(=O)Nc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 4.7 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
Off-targets reported?: No
Contributed by: Efrat Resnick
Calculated Values
MW: 1,035.26
Hbond donors: 4
Hbond acceptors: 14
cLogP: 8.32
TPSA: 217.39

SMILES: show
Cc1ccc(NC(=O)c2ccc(CN3CCN(CCCCCCOCCCCCOCCCCCC(=O)Nc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Linker type: non-PEG polyether
Incubation time (hours): 24
Cells: K562 CML
IC50: = 24 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
Contributed by: Efrat Resnick