Target: AR Androgen receptor P10275 Homo sapiens

E3 Ligand Binder

E3 ligase: VHL
E3 binder: Vh032
SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

Ligand

Ligand Name: Enzalutamide
IC₅₀: = 70 nM
SMILES: show

CNC(=O)c1ccc(N2C(=S)N(c3ccc(C#N)c(C(F)(F)F)c3)C(=O)C2(C)C)cc1F

Representative PROTAC (Active) name: 2c (ARCC-4) - status:Reviewed Edit

Calculated Values
MW: 1,024.20
Hbond donors: 3
Hbond acceptors: 11
cLogP: 8.58
TPSA: 177.43

SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCCCOc2ccc(-c3ccc(N4C(=S)N(c5ccc(C#N)c(C(F)(F)F)c5)C(=O)C4(C)C)cc3)cc2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 20
Cells: VCaP
IC₅₀: = 36 nM
DC₅₀: = 5 nM
D_max: = 98 %
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

Contributed by: Daniel Zaidman

PROTAC (Active) name: 2b - status:Reviewed Edit

Calculated Values
MW: 1,020.21
Hbond donors: 3
Hbond acceptors: 12
cLogP: 7.71
TPSA: 186.66

SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCCOCCCCCOc2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2)C(C)(C)C)cc1

Linker type: non-PEG polyether
Incubation time (hours): 20
Cells: VCaP
DC₅₀: = 15 nM
D_max: = 76 %
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

Contributed by: Daniel Zaidman

PROTAC (Active) name: 2a - status:Reviewed Edit

Calculated Values
MW: 1,008.16
Hbond donors: 3
Hbond acceptors: 13
cLogP: 6.16
TPSA: 195.89

SMILES: show

Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOc2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 20
Cells: VCaP
D_max: = 47 %
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

Contributed by: Daniel Zaidman