PROTACpedia - PROTACS on 31539241

Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase. J Med Chem. 2019 Oct 24;62(20):9281-9298. PMID:31539241 DOI:10.1021/acs.jmedchem.9b01264

Uniprot ID:
P00519

Target: ABL1 Tyrosine-protein kinase ABL1 P00519 Homo sapiens

E3 Ligand Binder

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

Ligand Name: Dasatinib
Ligand PDB Id: 1N1
PDB with Ligand: 2GQG
SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCO)CC2)n1

Representative PROTAC (Active) name: 19 (SIAIS178) - status:Reviewed Edit

Calculated Values
MW: 1,012.70
Hbond donors: 5
Hbond acceptors: 14
cLogP: 7.43
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 8.5 nM
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: EPHB4, RIPK2, Src, PDGFRβ, BTK

Contributed by: Ronen Gabizon

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

Calculated Values
MW: 998.68
Hbond donors: 5
Hbond acceptors: 14
cLogP: 7.04
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 17.9 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: Ronen Gabizon

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

Calculated Values
MW: 956.60
Hbond donors: 5
Hbond acceptors: 14
cLogP: 5.87
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 611 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: Ronen Gabizon

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

Calculated Values
MW: 1,026.73
Hbond donors: 5
Hbond acceptors: 14
cLogP: 7.82
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 37.9 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: Ronen Gabizon

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

Calculated Values
MW: 1,040.76
Hbond donors: 5
Hbond acceptors: 14
cLogP: 8.21
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 10.1 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
Off-targets reported?: No

Contributed by: Ronen Gabizon

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

Calculated Values
MW: 984.65
Hbond donors: 5
Hbond acceptors: 14
cLogP: 6.65
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 34.7 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: Ronen Gabizon

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

Calculated Values
MW: 970.62
Hbond donors: 5
Hbond acceptors: 14
cLogP: 6.26
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
DC₅₀: = 40.2 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: Ronen Gabizon

PROTAC (Inactive) name: 25 - status:Reviewed Edit

Calculated Values
MW: 1,027.67
Hbond donors: 6
Hbond acceptors: 15
cLogP: 5.38
TPSA: 244.08

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CNC(=O)CCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 15 - status:Reviewed Edit

Calculated Values
MW: 1,124.92
Hbond donors: 5
Hbond acceptors: 14
cLogP: 10.55
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCCCCCCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 10 - status:Reviewed Edit

Calculated Values
MW: 1,176.86
Hbond donors: 5
Hbond acceptors: 19
cLogP: 5.95
TPSA: 261.13

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCOCCOCCOCCOCCOCCC(=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: PEG
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 13 - status:Reviewed Edit

Calculated Values
MW: 1,044.70
Hbond donors: 5
Hbond acceptors: 16
cLogP: 5.90
TPSA: 233.44

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCOCCOCCC(=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: PEG
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 7 - status:Reviewed Edit

Calculated Values
MW: 1,158.93
Hbond donors: 5
Hbond acceptors: 17
cLogP: 8.73
TPSA: 225.60

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCCOCCOCCOCCCCCC(=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
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: Ronen Gabizon

PROTAC (Inactive) name: 11 - status:Reviewed Edit

Calculated Values
MW: 1,132.81
Hbond donors: 5
Hbond acceptors: 18
cLogP: 5.94
TPSA: 251.90

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCOCCOCCOCCOCCC(=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: PEG
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 9 - status:Reviewed Edit

Calculated Values
MW: 1,172.92
Hbond donors: 5
Hbond acceptors: 17
cLogP: 8.26
TPSA: 242.67

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCOCCOCCOCCCCCC(=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
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: Ronen Gabizon

PROTAC (Inactive) name: 16 - status:Reviewed Edit

Calculated Values
MW: 1,096.87
Hbond donors: 5
Hbond acceptors: 14
cLogP: 9.77
TPSA: 214.98

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCCCCCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 26 - status:Reviewed Edit

Calculated Values
MW: 1,139.89
Hbond donors: 6
Hbond acceptors: 15
cLogP: 8.50
TPSA: 244.08

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCCNC(=O)CCCCCCCCC(=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: Alkane
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 12 - status:Reviewed Edit

Calculated Values
MW: 1,088.75
Hbond donors: 5
Hbond acceptors: 17
cLogP: 5.92
TPSA: 242.67

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCOCCOCCOCCC(=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: PEG
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 24 - status:Reviewed Edit

Calculated Values
MW: 1,079.75
Hbond donors: 5
Hbond acceptors: 17
cLogP: 6.48
TPSA: 245.69

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)CCCc3cn(CCCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)nn3)CC2)n1

Linker type: Other
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 27 - status:Reviewed Edit

Calculated Values
MW: 1,125.91
Hbond donors: 6
Hbond acceptors: 15
cLogP: 8.97
TPSA: 227.01

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCCCCNC(=O)CCCCCCCCC(=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: Other
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon

PROTAC (Inactive) name: 14 - status:Reviewed Edit

Calculated Values
MW: 1,016.65
Hbond donors: 5
Hbond acceptors: 16
cLogP: 5.12
TPSA: 233.44

SMILES: show

Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(C(=O)COCCOCC(=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: PEG
Incubation time (hours): 24
Cells: K562
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: Ronen Gabizon