PROTACpedia
Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. J Med Chem. 2019 Dec 26;62(24):11218-11231. PMID:31804827 DOI:10.1021/acs.jmedchem.9b01393
Target: AR Androgen receptor P10275 Homo sapiens
E3 ligase: VHL
E3 binder: VH-E
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccc(Cl)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 949.98
Hbond donors: 3
Hbond acceptors: 9
cLogP: 8.01
TPSA: 178.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccc(Cl)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,033.11
Hbond donors: 3
Hbond acceptors: 10
cLogP: 8.48
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(Cl)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-G
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccccc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 915.53
Hbond donors: 3
Hbond acceptors: 9
cLogP: 7.36
TPSA: 178.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 0.5,1,3,6,12,24
Cells: LNCaP
DC50: = 0.5352 nM
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 946.59
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.44
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C3CN(c4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)C3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 970.61
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.04
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)C2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 68 %
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: Adi Rogel
Calculated Values
MW: 970.61
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.04
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)C3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 86 %
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: Adi Rogel
Calculated Values
MW: 946.59
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.16
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CC(c4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)C3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 892.50
Hbond donors: 3
Hbond acceptors: 10
cLogP: 6.42
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCN(c3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 998.67
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.82
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 891.51
Hbond donors: 3
Hbond acceptors: 9
cLogP: 7.48
TPSA: 178.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(c3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccccc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-D
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccc(Br)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 994.43
Hbond donors: 3
Hbond acceptors: 9
cLogP: 8.12
TPSA: 178.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccc(Br)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,077.56
Hbond donors: 3
Hbond acceptors: 10
cLogP: 8.59
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(Br)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 95 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-B
SMILES: show
C#Cc1ccc([C@H](CC(=O)NC)NC(=O)[C@H]2C[C@H](O)CN2C(=O)[C@@H](c2cc(C)no2)C(C)C)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 939.55
Hbond donors: 3
Hbond acceptors: 9
cLogP: 7.34
TPSA: 178.10

SMILES: show
C#Cc1ccc([C@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)NC(=O)[C@H]2C[C@H](O)CN2C(=O)[C@@H](c2cc(C)no2)C(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,022.69
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.81
TPSA: 181.34

SMILES: show
C#Cc1ccc([C@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)NC(=O)[C@H]2C[C@H](O)CN2C(=O)[C@@H](c2cc(C)no2)C(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-C
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccc(C#N)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 940.54
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.23
TPSA: 201.89

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccc(C#N)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,023.68
Hbond donors: 3
Hbond acceptors: 11
cLogP: 7.70
TPSA: 205.13

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(C#N)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-F
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccc(F)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 933.52
Hbond donors: 3
Hbond acceptors: 9
cLogP: 7.50
TPSA: 178.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccc(F)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,016.66
Hbond donors: 3
Hbond acceptors: 10
cLogP: 7.96
TPSA: 181.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(F)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-A
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](c1cc(C)no1)C(C)C)c1ccc(-c2scnc2C)cc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(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@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(N3CCC(C#Cc4ccc(C(=O)N[C@H]5C(C)(C)[C@H](Oc6ccc(C#N)c(Cl)c6)C5(C)C)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 0.5,1,3,6,12,24
Cells: LNCaP
DC50: = 7.2 nM
Dmax: > 99 %
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: Adi Rogel
Calculated Values
MW: 1,012.67
Hbond donors: 3
Hbond acceptors: 11
cLogP: 8.79
TPSA: 190.99

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@@H](O)C[C@@H]2C(=O)N[C@@H](CC(=O)N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: > 99 %
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: Adi Rogel
E3 ligase: VHL
E3 binder: VH-H
SMILES: show
CNC(=O)C[C@H](NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@@H](CNC(C)=O)C(C)C)c1ccccc1

 Ligand Name: Apalutamide analog
SMILES: show
CC1(C)[C@H](NC(=O)c2ccccc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Calculated Values
MW: 891.51
Hbond donors: 4
Hbond acceptors: 8
cLogP: 5.78
TPSA: 181.17

SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@@H](O)C[C@@H]1C(=O)N[C@@H](CC(=O)N1CCC(C#Cc2ccc(C(=O)N[C@H]3C(C)(C)[C@H](Oc4ccc(C#N)c(Cl)c4)C3(C)C)cc2)CC1)c1ccccc1)C(C)C

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: < 5 %
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: Adi Rogel
Calculated Values
MW: 988.67
Hbond donors: 4
Hbond acceptors: 9
cLogP: 6.50
TPSA: 184.41

SMILES: show
CC(=O)NC[C@H](C(=O)N1C[C@@H](O)C[C@@H]1C(=O)N[C@@H](CC(=O)N1CCC(N2CCC(C#Cc3ccc(C(=O)N[C@H]4C(C)(C)[C@H](Oc5ccc(C#N)c(Cl)c5)C4(C)C)cc3)CC2)CC1)c1ccccc1)C(C)C

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 11 %
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: Adi Rogel