PROTACpedia
Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment. Neoplasia. 2020 Jan 10;22(2):111-119. PMID:31931431 DOI:10.1016/j.neo.2019.12.003
Target: AR Androgen receptor P10275 Homo sapiens
E3 ligase: VHL
E3 binder: VH Ligand 6
SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NCc2ccc(-c3scnc3C)cc2)C(C)C)on1

 Ligand Name: Enzalutamide
SMILES: show
CNC(=O)c1ccc(N2C(=S)N(c3ccc(C#N)c(C(F)(F)F)c3)C(=O)C2(C)C)cc1F

Calculated Values
MW: 1,102.32
Hbond donors: 2
Hbond acceptors: 12
cLogP: 8.93
TPSA: 179.45

SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NC(CC(=O)N2CCC(N3CCC(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LnCap
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
Contributed by: Paul Gehrtz
E3 ligase: VHL
E3 binder: VH Ligand 6
SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NCc2ccc(-c3scnc3C)cc2)C(C)C)on1

 Ligand Name: Apalutamide
SMILES: show
CNC(=O)c1ccc(N2C(=S)N(c3cnc(C#N)c(C(F)(F)F)c3)C(=O)C23CCC3)cc1F

Calculated Values
MW: 1,115.32
Hbond donors: 2
Hbond acceptors: 13
cLogP: 8.46
TPSA: 192.34

SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NC(CC(=O)N2CCC(N3CCC(C#Cc4ccc(N5C(=S)N(c6cnc(C#N)c(C(F)(F)F)c6)C(=O)C56CCC6)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LnCap
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
Contributed by: Paul Gehrtz
E3 ligase: VHL
E3 binder: VH Ligand 6
SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NCc2ccc(-c3scnc3C)cc2)C(C)C)on1

 Ligand Name: ARI-16
SMILES: show
CC1(C)C(NC(=O)c2cnn(CCO)c2)C(C)(C)C1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 1,095.81
Hbond donors: 3
Hbond acceptors: 12
cLogP: 9.26
TPSA: 194.23

SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NC(CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)NC5C(C)(C)C(Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LnCap
DC50: = 8.0 nM
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Paul Gehrtz
E3 ligase: VHL
E3 binder: VH Ligand 6
SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NCc2ccc(-c3scnc3C)cc2)C(C)C)on1

 Ligand Name: Bicalutamide
SMILES: show
CC(O)(CS(=O)(=O)c1ccc(F)cc1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1

Calculated Values
MW: 1,125.31
Hbond donors: 4
Hbond acceptors: 14
cLogP: 7.17
TPSA: 239.37

SMILES: show
Cc1cc(C(C(=O)N2C[C@H](O)CC2C(=O)NC(CC(=O)N2CCC(N3CCC(C#Cc4ccc(S(=O)(=O)CC(C)(O)C(=O)Nc5ccc(C#N)c(C(F)(F)F)c5)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LnCap
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
Contributed by: Paul Gehrtz