PROTACpedia
Exploring Targeted Degradation Strategy for Oncogenic KRAS(G12C). Cell Chem Biol. 2020 Jan 16;27(1):19-31.e6. PMID:31883964 DOI:10.1016/j.chembiol.2019.12.006
Target: KRAS GTPase KRas, N-terminally processed P01116 Homo sapiens
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: Compound 1
Ligand PDB Id: 91G
PDB with Ligand: 5V9O
SMILES: show
C=CC(=O)N1CCN(c2ncnc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Calculated Values
MW: 917.44
Hbond donors: 4
Hbond acceptors: 13
cLogP: 5.11
TPSA: 183.65

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCN3CCN(CCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 32 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: No
Comments: Engagment was tested in-vitro
Contributed by: Efrat Resnick
Calculated Values
MW: 917.44
Hbond donors: 4
Hbond acceptors: 13
cLogP: 5.11
TPSA: 183.65

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCN3CCN(CCCNc4ccc5c(c4)C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 35 %
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: 936.40
Hbond donors: 5
Hbond acceptors: 14
cLogP: 4.25
TPSA: 224.73

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCC(=O)NCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
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: 862.36
Hbond donors: 4
Hbond acceptors: 12
cLogP: 5.42
TPSA: 180.41

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCN(C)CCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 25 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: No
Comments: Engagment was tested in-vitro
Contributed by: Efrat Resnick
Calculated Values
MW: 954.41
Hbond donors: 3
Hbond acceptors: 15
cLogP: 4.74
TPSA: 211.29

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCOCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: PEG
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 6 %
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: 1,024.50
Hbond donors: 5
Hbond acceptors: 16
cLogP: 4.28
TPSA: 243.19

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCC(=O)NCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
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: 991.52
Hbond donors: 4
Hbond acceptors: 15
cLogP: 4.75
TPSA: 202.11

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCCN3CCN(CCOCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 10 %
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: 917.48
Hbond donors: 4
Hbond acceptors: 11
cLogP: 8.61
TPSA: 177.17

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCCCCCCCCCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Alkane
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 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
Contributed by: Efrat Resnick
Calculated Values
MW: 910.36
Hbond donors: 3
Hbond acceptors: 14
cLogP: 4.72
TPSA: 202.06

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: PEG
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 7 %
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: 1,032.53
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.26
TPSA: 235.57

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCc3cn(CCOCCOCCOCCC(=O)Nc4cccc5c4CN(C4CCC(=O)NC4=O)C5=O)nn3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
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: 998.46
Hbond donors: 3
Hbond acceptors: 16
cLogP: 4.76
TPSA: 220.52

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCOCCOCCOCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: PEG
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 3 %
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: 865.32
Hbond donors: 4
Hbond acceptors: 13
cLogP: 4.74
TPSA: 195.63

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCNc3ccc4c(c3)C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: PEG
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 4 %
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: 945.50
Hbond donors: 4
Hbond acceptors: 13
cLogP: 5.89
TPSA: 183.65

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCCCN3CCN(CCCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 17 %
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: 1,150.66
Hbond donors: 4
Hbond acceptors: 19
cLogP: 4.92
TPSA: 263.26

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCOCCc3cn(CCOCCOCCOCCC(=O)Nc4cccc5c4CN(C4CCC(=O)NC4=O)C5=O)nn3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
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: 889.39
Hbond donors: 4
Hbond acceptors: 13
cLogP: 4.33
TPSA: 183.65

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCN3CCN(CCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: Other
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 24 %
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: 909.37
Hbond donors: 4
Hbond acceptors: 14
cLogP: 4.76
TPSA: 204.86

SMILES: show
C=CC(=O)N1CCN(c2nc(NCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nc3c(F)c(-c4cc(O)cc5ccccc45)c(Cl)cc23)CC1

Linker type: PEG
Incubation time (hours): 16
Cells: GFP-KRASG12C reporter cell line in Flp-In 293
Dmax: = 19 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: Yes
Off-targets reported?: No
Comments: Engagment was tested in-vitro
Contributed by: Efrat Resnick