PROTACpedia
Selective degradation of CDK6 by a palbociclib based PROTAC. Bioorg Med Chem Lett. 2019 Jun 1;29(11):1375-1379. PMID:30935795 DOI:10.1016/j.bmcl.2019.03.035
Target: CDK6 Cyclin-dependent kinase 6 Q00534 Homo sapiens
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: 964.09
Hbond donors: 4
Hbond acceptors: 18
cLogP: 3.14
TPSA: 248.62

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCCOCCOCCOCCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 4,24
Cells: MiaPaCa2, HPNE
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: Amit Shraga
Calculated Values
MW: 816.92
Hbond donors: 3
Hbond acceptors: 14
cLogP: 4.28
TPSA: 208.90

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCCC(=O)Nc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 4,24
Cells: MiaPaCa2
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: Amit Shraga
Calculated Values
MW: 874.02
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.24
TPSA: 220.93

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(C(=O)NCCCCCCCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 4,24
Cells: MiaPaCa2
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: Amit Shraga
Calculated Values
MW: 850.93
Hbond donors: 3
Hbond acceptors: 17
cLogP: 3.16
TPSA: 219.52

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCONc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 4,24
Cells: MiaPaCa2
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: Amit Shraga
Calculated Values
MW: 817.91
Hbond donors: 4
Hbond acceptors: 14
cLogP: 3.68
TPSA: 220.93

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(C(=O)NCCCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Alkane
Incubation time (hours): 4,24
Cells: MiaPaCa2
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: Amit Shraga