PROTACpedia
Development of selective small molecule MDM2 degraders based on nutlin. Eur J Med Chem. 2019 Aug 15;176:476-491. PMID:31128449 DOI:10.1016/j.ejmech.2019.05.046
Target: MDM2 E3 ubiquitin-protein ligase Mdm2 Q00987 Homo sapiens
E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show
Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

 Ligand Name: RG7112 analogue
Ligand PDB Id: 1F0
PDB with Ligand: 4IPF
SMILES: show
O=C(N1CCNCC1)N2C(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC

Calculated Values
MW: 859.85
Hbond donors: 1
Hbond acceptors: 7
cLogP: 7.78
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCN3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
EC50 (cells): = 7.2 nM
DC50: ~ 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
Off-targets reported?: No
Contributed by: Yangwode Jing, Ronen Gabizon
Calculated Values
MW: 972.97
Hbond donors: 2
Hbond acceptors: 8
cLogP: 7.60
TPSA: 161.03

SMILES: show
O=C(NCC(N1CCN(C(N2C(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC)=O)CC1)=O)CCCC#CC6=CC=CC7=C6CN(C(CC8)C(NC8=O)=O)C7=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 901.89
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.09
TPSA: 131.93

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCC(N3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)=O)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 929.95
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.87
TPSA: 131.93

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCCCC(N3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)=O)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 873.88
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.17
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCN3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 915.92
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.48
TPSA: 131.93

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCCC(N3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)=O)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 887.91
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.56
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCCN3CCN(C(N4C(C5=CC=C(Cl)C=C5)C(C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 987.00
Hbond donors: 2
Hbond acceptors: 8
cLogP: 7.99
TPSA: 161.03

SMILES: show
O=C(NCC(N1CCN(C(N2C(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC)=O)CC1)=O)CCCCC#CC6=CC=CC7=C6CN(C(CC8)C(NC8=O)=O)C7=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 958.94
Hbond donors: 2
Hbond acceptors: 8
cLogP: 7.21
TPSA: 161.03

SMILES: show
O=C(NCC(N1CCN(C(N2C(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC)=O)CC1)=O)CCC#CC6=CC=CC7=C6CN(C(CC8)C(NC8=O)=O)C7=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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
E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show
Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

 Ligand Name: (4S,5R)-RG7112 analogue
Ligand PDB Id: 1F0
PDB with Ligand: 4IPF
SMILES: show
O=C(N1CCNCC1)N2[C@H](C3=CC=C(Cl)C=C3)[C@H](C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC

Calculated Values
MW: 859.85
Hbond donors: 1
Hbond acceptors: 7
cLogP: 7.78
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCN3CCN(C(N4[C@H](C5=CC=C(Cl)C=C5)[C@H](C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
EC50 (cells): = 3.2 nM
DC50: = 23 nM
Dmax: = 90 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Yangwode Jing
Calculated Values
MW: 873.88
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.17
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCN3CCN(C(N4[C@H](C5=CC=C(Cl)C=C5)[C@H](C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 887.91
Hbond donors: 1
Hbond acceptors: 7
cLogP: 8.56
TPSA: 114.86

SMILES: show
O=C(C(N(CC1=C2C=CC=C1C#CCCCN3CCN(C(N4[C@H](C5=CC=C(Cl)C=C5)[C@H](C6=CC=C(Cl)C=C6)N=C4C7=CC=C(C(C)(C)C)C=C7OCC)=O)CC3)C2=O)CC8)NC8=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: RG7112 analogue
Ligand PDB Id: 1F0
PDB with Ligand: 4IPF
SMILES: show
O=C(N1CCNCC1)N2C(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC

Calculated Values
MW: 892.84
Hbond donors: 2
Hbond acceptors: 9
cLogP: 7.01
TPSA: 161.03

SMILES: show
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCC(N4CCN(C(N5C(C6=CC=C(Cl)C=C6)C(C7=CC=C(Cl)C=C7)N=C5C8=CC=C(C(C)(C)C)C=C8OCC)=O)CC4)=O)=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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: 835.79
Hbond donors: 1
Hbond acceptors: 8
cLogP: 7.58
TPSA: 131.93

SMILES: show
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3N4CCN(C(N5C(C6=CC=C(Cl)C=C6)C(C7=CC=C(Cl)C=C7)N=C5C8=CC=C(C(C)(C)C)C=C8OCC)=O)CC4)=O

Linker type: Other
Incubation time (hours): 6
Cells: RS4;11
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