PROTACpedia
Delineating the role of cooperativity in the design of potent PROTACs for BTK. Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7285-E7292. PMID:30012605 DOI:10.1073/pnas.1803662115
Target: BTK Tyrosine-protein kinase BTK Q06187 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: PF-06250112
IC50: = 0.5 nM
SMILES: show
N#CN1CCC[C@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1

Calculated Values
MW: 976.99
Hbond donors: 4
Hbond acceptors: 17
cLogP: 3.67
TPSA: 267.43

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCOCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 61 nM
DC50: < 37.4 nM
Dmax: > 80 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: ZFP91, IKZF1, IKZF3, ZNF827
Comments: Ligand name is from PMID 24068666. DCmax is 80-87%. DC50 is 1.1 - 37.4 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 844.83
Hbond donors: 4
Hbond acceptors: 14
cLogP: 3.62
TPSA: 239.74

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 1150 nM
DC50: < 1994.5 nM
Dmax: < 64 %
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: Ligand name is from PMID 24068666. DCmax is 36-64%. DC50 is 1487 - 1994.5 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 814.80
Hbond donors: 4
Hbond acceptors: 13
cLogP: 3.01
TPSA: 230.51

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)COCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 489 nM
Dmax: < 34 %
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: Ligand name is from PMID 24068666. DCmax is 15-34%
Contributed by: Adi Rogel
Calculated Values
MW: 946.96
Hbond donors: 4
Hbond acceptors: 16
cLogP: 3.06
TPSA: 258.20

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)COCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 0.02,0.5,1,2,4,6,8,24,32,48
Cells: Ramos, THP-1
IC50: = 74 nM
DC50: < 217.7 nM
Dmax: > 71 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: No
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: TEC, ZFP91, IKZF1, IKZF3, ZNF827
Comments: Ligand name is from PMID 24068666. DCmax is 71-85%. DC50 is 5.9 - 217.7 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 800.78
Hbond donors: 4
Hbond acceptors: 13
cLogP: 3.61
TPSA: 230.51

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 1535 nM
Dmax: < 33 %
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: Ligand name is from PMID 24068666. DCmax is 18-33%
Contributed by: Adi Rogel
Calculated Values
MW: 902.91
Hbond donors: 4
Hbond acceptors: 15
cLogP: 3.04
TPSA: 248.97

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)COCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 79 nM
DC50: < 469.9 nM
Dmax: > 63 %
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: Ligand name is from PMID 24068666. DCmax is 63-84%. DC50 is 21.8 - 469.9 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 991.01
Hbond donors: 4
Hbond acceptors: 17
cLogP: 3.08
TPSA: 267.43

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)COCCOCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 138 nM
DC50: < 184.1 nM
Dmax: > 70 %
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: Ligand name is from PMID 24068666. DCmax is 70-85%. DC50 is 9.7 - 184.1 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 888.88
Hbond donors: 4
Hbond acceptors: 15
cLogP: 3.64
TPSA: 248.97

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 71 nM
DC50: < 398.5 nM
Dmax: > 68 %
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: Ligand name is from PMID 24068666. DCmax is 68-85%. DC50 is 36.9 - 398.5 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 932.93
Hbond donors: 4
Hbond acceptors: 16
cLogP: 3.65
TPSA: 258.20

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 80 nM
DC50: < 90.5 nM
Dmax: > 75 %
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: Ligand name is from PMID 24068666. DCmax is 75-87%. DC50 is 4.5 - 90.5 nM.
Contributed by: Adi Rogel
Calculated Values
MW: 770.75
Hbond donors: 4
Hbond acceptors: 12
cLogP: 3.00
TPSA: 221.28

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)COCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 1400 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: Ligand name is from PMID 24068666
Contributed by: Adi Rogel
Calculated Values
MW: 756.72
Hbond donors: 4
Hbond acceptors: 12
cLogP: 3.59
TPSA: 221.28

SMILES: show
NC(=O)c1c(-c2ccc(Oc3ccc(F)cc3F)cc2)nn([C@H]2CCCN(C(=O)OCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)C2)c1N

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
IC50: = 735 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: Ligand name is from PMID 24068666
Contributed by: Adi Rogel
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2[nH]cnc2C)cc1)C(C)(C)C

 Ligand Name: PF-06250112
SMILES: show
N#CN1CCC[C@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1

Calculated Values
MW: 1,173.33
Hbond donors: 6
Hbond acceptors: 17
cLogP: 4.85
TPSA: 299.27

SMILES: show
Cc1nc[nH]c1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOCCOCCOCCOCCOCCC(=O)N2CCC[C@@H](n3nc(-c4ccc(Oc5ccc(F)cc5F)cc4)c(C(N)=O)c3N)C2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
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: Ligand name is from PMID 24068666
Contributed by: Adi Rogel
Calculated Values
MW: 1,129.27
Hbond donors: 6
Hbond acceptors: 16
cLogP: 4.84
TPSA: 290.04

SMILES: show
Cc1nc[nH]c1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOCCOCCOCCOCCC(=O)N2CCC[C@@H](n3nc(-c4ccc(Oc5ccc(F)cc5F)cc4)c(C(N)=O)c3N)C2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 24
Cells: Ramos, THP-1
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: Ligand name is from PMID 24068666
Contributed by: Adi Rogel