Target: ABL1 Tyrosine-protein kinase ABL1 P00519 Homo sapiens

E3 Ligand Binder

E3 ligase: Iap
E3 binder: Bestatin
SMILES: show

CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)Cc1ccccc1)C(=O)O

Ligand

Ligand Name: imatinib
Ligand PDB Id: STI
PDB with Ligand: 2HYY
SMILES: show

Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

Representative PROTAC (Active) name: SNIPER(ABL)-2 - status:Reviewed Edit

Calculated Values
MW: 842.06
Hbond donors: 7
Hbond acceptors: 10
cLogP: 6.38
TPSA: 213.35

SMILES: show

CC(C[C@H](C(NCCCCCCCC(NCC1=CC=C(C(NC2=CC(NC3=NC=CC(C4=CN=CC=C4)=N3)=C(C=C2)C)=O)C=C1)=O)=O)NC([C@@H]([C@H](Cc5ccccc5)N)O)=O)C

Linker type: Alkane
Incubation time (hours): 8, 24
Cells: K562
DC₅₀: ~ 30 μM
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

Comments: BCR-ABL degredation

Contributed by: Yangwode Jing, Ronen Gabizon

PROTAC (Active) name: SNIPER(ABL)-3 - status:Reviewed Edit

Calculated Values
MW: 856.09
Hbond donors: 7
Hbond acceptors: 10
cLogP: 6.77
TPSA: 213.35

SMILES: show

CC(C[C@H](C(NCCCCCCCCC(NCC1=CC=C(C(NC2=CC(NC3=NC=CC(C4=CN=CC=C4)=N3)=C(C=C2)C)=O)C=C1)=O)=O)NC([C@@H]([C@H](Cc5ccccc5)N)O)=O)C

Comments: BCR-ABL degredation

Contributed by: Yangwode Jing, Ronen Gabizon

PROTAC (Inactive) name: SNIPER(ABL)-1 - status:Reviewed Edit

Calculated Values
MW: 828.03
Hbond donors: 7
Hbond acceptors: 10
cLogP: 5.99
TPSA: 213.35

SMILES: show

CC(C[C@H](C(NCCCCCCC(NCC1=CC=C(C(NC2=CC(NC3=NC=CC(C4=CN=CC=C4)=N3)=C(C=C2)C)=O)C=C1)=O)=O)NC([C@@H]([C@H](Cc5ccccc5)N)O)=O)C

Linker type: Alkane
Incubation time (hours): 8, 24
Cells: K562
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

Comments: BCR-ABL degredation

Contributed by: Yangwode Jing