PROTACpedia
Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs. Bioorg Med Chem Lett. 2020 May 1;30(9):127106. PMID:32184044 DOI:10.1016/j.bmcl.2020.127106
Target: CDK6 Cyclin-dependent kinase 6 Q00534 Homo sapiens
E3 ligase: Iap
E3 binder: Iap Ligand
SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](N)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 1,059.23
Hbond donors: 5
Hbond acceptors: 17
cLogP: 3.87
TPSA: 243.58

SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)COCCOCCOCCN2CCN(c3ccc(Nc4ncc5c(C)c(C(C)=O)c(=O)n(C6CCCC6)c5n4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,129.32
Hbond donors: 6
Hbond acceptors: 17
cLogP: 3.98
TPSA: 259.79

SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)CCOCCOCCOCCNC(=O)CN2CCN(c3ccc(Nc4cc5c(cn4)c(C)c(C(C)=O)c(=O)n5C4CCCC4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 831.93
Hbond donors: 4
Hbond acceptors: 15
cLogP: 3.09
TPSA: 220.93

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 891.99
Hbond donors: 4
Hbond acceptors: 17
cLogP: 2.34
TPSA: 239.39

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 1,064.32
Hbond donors: 4
Hbond acceptors: 18
cLogP: 5.53
TPSA: 235.57

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCOCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman
Calculated Values
MW: 1,135.40
Hbond donors: 5
Hbond acceptors: 19
cLogP: 5.04
TPSA: 264.67

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCOCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: inactive for CDK4, active for CDK6
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,016.33
Hbond donors: 4
Hbond acceptors: 15
cLogP: 7.82
TPSA: 207.88

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCCCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Target: CDK4 Cyclin-dependent kinase 4 P11802 Homo sapiens
E3 ligase: Iap
E3 binder: Iap Ligand
SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](N)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 1,059.23
Hbond donors: 5
Hbond acceptors: 17
cLogP: 3.87
TPSA: 243.58

SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)COCCOCCOCCN2CCN(c3ccc(Nc4ncc5c(C)c(C(C)=O)c(=O)n(C6CCCC6)c5n4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,129.32
Hbond donors: 6
Hbond acceptors: 17
cLogP: 3.98
TPSA: 259.79

SMILES: show
CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)CCOCCOCCOCCNC(=O)CN2CCN(c3ccc(Nc4cc5c(cn4)c(C)c(C(C)=O)c(=O)n5C4CCCC4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 831.93
Hbond donors: 4
Hbond acceptors: 15
cLogP: 3.09
TPSA: 220.93

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 891.99
Hbond donors: 4
Hbond acceptors: 17
cLogP: 2.34
TPSA: 239.39

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

 Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Calculated Values
MW: 1,135.40
Hbond donors: 5
Hbond acceptors: 19
cLogP: 5.04
TPSA: 264.67

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCOCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: inactive for CDK4, active for CDK6
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,016.33
Hbond donors: 4
Hbond acceptors: 15
cLogP: 7.82
TPSA: 207.88

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCCCCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 24
Cells: Jurkat
Tested a non-binding E3 control?: No
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,064.32
Hbond donors: 4
Hbond acceptors: 18
cLogP: 5.53
TPSA: 235.57

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCOCC(=O)N[C@H](C(=O)N5C[C@H](O)C[C@H]5C(=O)N[C@@H](C)c5ccc(-c6scnc6C)cc5)C(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 24
Cells: Jurkat
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: Daniel Zaidman