PROTACpedia
Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines. Eur J Med Chem. 2020 Aug 1;199:112397. PMID:32388279 DOI:10.1016/j.ejmech.2020.112397
Target: BCL2L1 Bcl-2-like protein 1 Q07817 Homo sapiens
E3 ligase: Iap
E3 binder: LCL161
SMILES: show
C[C@H](NC)C(N[C@@H](C1CCCCC1)C(N2[C@H](C3=NC(C(C4=CC=C(F)C=C4)=O)=CS3)CCC2)=O)=O

 Ligand Name: ABT-263
Ligand PDB Id: 1XJ
PDB with Ligand: 4QNQ
SMILES: show
CC1(C)CCC(c2ccc(Cl)cc2)=C(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(N[C@H](CCN5CCOCC5)CSc5ccccc5)c(S(=O)(=O)C(F)(F)F)c4)cc3)CC2)C1

Calculated Values
MW: 1,753.61
Hbond donors: 4
Hbond acceptors: 24
cLogP: 12.37
TPSA: 298.47

SMILES: show
O=C(NS(=O)(C1=CC=C(N[C@H](CCN2CCN(C(CCCN3N=NC(COCCOCCOCCOC4=CC=CC(C(C5=CSC([C@H]6N(C([C@@H](C7CCCCC7)NC([C@@H](NC)C)=O)=O)CCC6)=N5)=O)=C4)=C3)=O)CC2)CSC8=CC=CC=C8)C(S(=O)(C(F)(F)F)=O)=C1)=O)C9=CC=C(N%10CCN(CC%11=C(C%12=CC=C(Cl)C=C%12)CCC(C)(C)C%11)CC%10)C=C9

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 147 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: Yangwode Jing
Calculated Values
MW: 1,600.43
Hbond donors: 4
Hbond acceptors: 20
cLogP: 11.78
TPSA: 258.53

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(COCCOCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 143 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,554.40
Hbond donors: 4
Hbond acceptors: 18
cLogP: 12.92
TPSA: 240.07

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 1959 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,709.56
Hbond donors: 4
Hbond acceptors: 23
cLogP: 12.35
TPSA: 289.24

SMILES: show
O=C(NS(=O)(C1=CC=C(N[C@H](CCN2CCN(C(CCCN3N=NC(COCCOCCOC4=CC=CC(C(C5=CSC([C@H]6N(C([C@@H](C7CCCCC7)NC([C@@H](NC)C)=O)=O)CCC6)=N5)=O)=C4)=C3)=O)CC2)CSC8=CC=CC=C8)C(S(=O)(C(F)(F)F)=O)=C1)=O)C9=CC=C(N%10CCN(CC%11=C(C%12=CC=C(Cl)C=C%12)CCC(C)(C)C%11)CC%10)C=C9

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 157 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: Yangwode Jing
Calculated Values
MW: 1,688.53
Hbond donors: 4
Hbond acceptors: 22
cLogP: 11.81
TPSA: 276.99

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(COCCOCCOCCOCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 75 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,540.37
Hbond donors: 4
Hbond acceptors: 18
cLogP: 12.53
TPSA: 240.07

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 997 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,582.46
Hbond donors: 4
Hbond acceptors: 18
cLogP: 13.70
TPSA: 240.07

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,568.43
Hbond donors: 4
Hbond acceptors: 18
cLogP: 13.31
TPSA: 240.07

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCCOC8=CC=CC(C(C9=CSC([C@H]%10N(CCC%10)C([C@H](NC([C@H](C)NC)=O)C%11CCCCC%11)=O)=N9)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
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
Contributed by: Ronen Gabizon
E3 ligase: Iap
E3 binder: L2
SMILES: show
O=C([C@H]1C(C)(C)C[C@@]([H])(OCC[C@H]2NC([C@@H](C)NC)=O)N1C2=O)N[C@@H]3CCCC4=CC(O)=CC=C43

 Ligand Name: ABT-263
Ligand PDB Id: 1XJ
PDB with Ligand: 4QNQ
SMILES: show
CC1(C)CCC(c2ccc(Cl)cc2)=C(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(N[C@H](CCN5CCOCC5)CSc5ccccc5)c(S(=O)(=O)C(F)(F)F)c4)cc3)CC2)C1

Calculated Values
MW: 1,574.36
Hbond donors: 5
Hbond acceptors: 19
cLogP: 9.72
TPSA: 266.90

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(COCCOCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 100 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,676.50
Hbond donors: 5
Hbond acceptors: 21
cLogP: 10.14
TPSA: 285.36

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(COCCOCCOCCOCCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: PEG
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 70 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,514.31
Hbond donors: 5
Hbond acceptors: 17
cLogP: 10.46
TPSA: 248.44

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 62 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,542.36
Hbond donors: 5
Hbond acceptors: 17
cLogP: 11.24
TPSA: 248.44

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 127 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,528.34
Hbond donors: 5
Hbond acceptors: 17
cLogP: 10.85
TPSA: 248.44

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 76 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,683.50
Hbond donors: 5
Hbond acceptors: 22
cLogP: 10.29
TPSA: 297.61

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCN8N=NC(COCCOCCOC9=CC=C%10C(CCC[C@H]%10NC([C@H]%11C(C)(C)C[C@@]([H])(OCC[C@H]%12NC([C@@H](C)NC)=O)N%11C%12=O)=O)=C9)=C8)=O)=O

Linker type: non-PEG polyether
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 153 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,556.39
Hbond donors: 5
Hbond acceptors: 17
cLogP: 11.63
TPSA: 248.44

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCCCCOC8=CC=C9C(CCC[C@H]9NC([C@H]%10C(C)(C)C[C@@]([H])(OCC[C@H]%11NC([C@@H](C)NC)=O)N%10C%11=O)=O)=C8)=O)=O

Linker type: Alkane
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 274 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
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,727.55
Hbond donors: 5
Hbond acceptors: 23
cLogP: 10.31
TPSA: 306.84

SMILES: show
O=C(C1=CC=C(C=C1)N2CCN(CC2)CC3=C(CCC(C)(C3)C)C4=CC=C(C=C4)Cl)NS(=O)(C5=CC=C(C(S(=O)(C(F)(F)F)=O)=C5)N[C@@H](CSC6=CC=CC=C6)CCN7CCN(CC7)C(CCCN8N=NC(COCCOCCOCCOC9=CC=C%10C(CCC[C@H]%10NC([C@H]%11C(C)(C)C[C@@]([H])(OCC[C@H]%12NC([C@@H](C)NC)=O)N%11C%12=O)=O)=C9)=C8)=O)=O

Linker type: non-PEG polyether
Incubation time (hours): 72
Cells: MyLa1929
EC50 (cells): = 119 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
Contributed by: Ronen Gabizon