Target: BTK Tyrosine-protein kinase BTK Q06187 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: Ibrutinib
Ligand PDB Id: "8E8"
PDB with Ligand: 5P9J
SMILES: show

C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1

Representative PROTAC (Active) name: P13I - status:Reviewed Edit

Calculated Values
MW: 912.96
Hbond donors: 3
Hbond acceptors: 18
cLogP: 3.50
TPSA: 253.14

SMILES: show

Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2[C@@H]1CCCN(C(=O)c2cn(CCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)nn2)C1

Linker type: Other
Incubation time (hours): 4,8,12,24
Cells: HBL1, Ramos, Mino, IgE MM
DC₅₀: < 11.4 nM
D_max: = 94 %
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

Comments: also degrades ibrutinib-resistant C481S BTK. DC50 is 6.3 nM (HBL1), 8.5 nM (Ramos), 9.2 nM (Mino), 11.4 nM (IgE MM)

Contributed by: Adi Rogel