Target: BCL2L1 Bcl-2-like protein 1 Q07817 Homo sapiens

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Ligand

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

CN(C)CC#Cc1ccc(OCCCc2sc(N3CCc4cccc(C(=O)Nc5nc6ccccc6s5)c4C3)nc2C(=O)O)c(F)c1

Representative PROTAC (Active) name: XZ424 - status:Reviewed Edit

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

SMILES: show

O=C1CCC(N2C(=O)c3cccc(NCCOCCOCc4cn(CCCC(=O)N5CCN(CC#Cc6ccc(OCCCc7sc(N8CCc9cccc(C(=O)Nc%10nc%11ccccc%11s%10)c9C8)nc7C(=O)O)c(F)c6)CC5)nn4)c3C2=O)C(=O)N1

Linker type: non-PEG polyether
Incubation time (hours): 16
Cells: MOLT4
IC₅₀: = 0.009 nM
DC₅₀: = 50 nM
D_max: = 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