Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. Chem Commun (Camb). 2019 Dec 5;55(98):14765-14768. PMID:31754664 DOI:10.1039/c9cc07217a
Target: BCL2L1 Bcl-2-like protein 1 Q07817 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Ligand Name: A-1155463
Ligand PDB Id: 3CQ
PDB with Ligand: 4QVX
IC50: = 0.005 nM
SMILES: show

Calculated Values
MW: 1,221.36
Hbond donors: 4
Hbond acceptors: 20
cLogP: 6.03
TPSA: 272.95

SMILES: show

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: MOLT4
IC50: = 0.009 nM
DC50: = 50 nM
Dmax: = 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Comments: Selective BCLXL degradation: only in MOLT4 cells, not platelets
Contributed by: Paul Gehrtz