PROTACpedia
Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML. Cell Chem Biol. 2019 Feb 21;26(2):300-306.e9. PMID:30595531 DOI:10.1016/j.chembiol.2018.11.006
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: 937.02
Hbond donors: 3
Hbond acceptors: 18
cLogP: 2.32
TPSA: 245.82

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCOCCNC(=O)COc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 4
Cells: AML cells, CRBN-/-
Dmax: ~ 100 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: No
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: No
Contributed by: Daniel Zaidman
Calculated Values
MW: 936.04
Hbond donors: 4
Hbond acceptors: 18
cLogP: 2.36
TPSA: 248.62

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 4
Cells: AML cells
Dmax: ~ 100 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: CDK4, IKZF1, IKZF3
Contributed by: Daniel Zaidman
Target: CDK4 Cyclin-dependent kinase 4 P11802 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: 936.04
Hbond donors: 4
Hbond acceptors: 18
cLogP: 2.36
TPSA: 248.62

SMILES: show
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: PEG
Incubation time (hours): 4
Cells: AML cells
Dmax: ~ 100 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: CDK4, IKZF1, IKZF3
Contributed by: Daniel Zaidman