PROTACpedia
Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer. J Med Chem. 2019 Jan 24;62(2):941-964. PMID:30629437 DOI:10.1021/acs.jmedchem.8b01631
Target: AR Androgen receptor P10275 Homo sapiens
E3 ligase: VHL
E3 binder: Vh032 Analog
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: Enzalutamide (analog)
SMILES: show
Cc1ccc(Cc2c(C)nn(-c3ccc(C#N)c(Cl)c3)c2C)cc1

Calculated Values
MW: 1,034.73
Hbond donors: 2
Hbond acceptors: 12
cLogP: 9.04
TPSA: 173.72

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(Cc5c(C)nn(-c6ccc(C#N)c(Cl)c6)c5C)cc4)CC3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 93 %
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
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](N)C(C)(C)C)cc1

 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: 1,087.31
Hbond donors: 3
Hbond acceptors: 12
cLogP: 7.99
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 92 %
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
Calculated Values
MW: 1,101.33
Hbond donors: 3
Hbond acceptors: 12
cLogP: 8.38
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 89 %
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
Calculated Values
MW: 1,073.28
Hbond donors: 3
Hbond acceptors: 12
cLogP: 7.60
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 78 %
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
Calculated Values
MW: 1,059.25
Hbond donors: 3
Hbond acceptors: 12
cLogP: 7.21
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 31 %
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
Calculated Values
MW: 1,045.23
Hbond donors: 3
Hbond acceptors: 11
cLogP: 7.81
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)N2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 12 %
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
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)cc1

 Ligand Name: Enzalutamide (analog)
SMILES: show
Cc1ccc(C(=O)N[C@H]2C(C)(C)[C@H](Oc3ccc(C#N)c(Cl)c3)C2(C)C)cc1

Calculated Values
MW: 1,129.84
Hbond donors: 4
Hbond acceptors: 11
cLogP: 8.55
TPSA: 197.30

SMILES: show
Cc1ncsc1-c1ccc([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](NC(=O)C2(F)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6,24
Cells: LNCaP, VCaP, and 22Rv
DC50: < 10.4 nM
Dmax: > 95 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Comments: DC50 is 0.86nM in LNCaP, 0.76 in VCaP and 10.4 nM at 1uM in 22Rv1. EC50 in cells is 0.25nM for LNCaP, 0.34 nM for VCaP, 183nM for 22Rv1.
Contributed by: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
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: Enzalutamide (analog)
SMILES: show
Cc1ccc(S(=O)CC(C)(O)C(=O)Nc2ccc(C#N)c(C(F)(F)F)c2)cc1

Calculated Values
MW: 1,109.31
Hbond donors: 4
Hbond acceptors: 13
cLogP: 7.51
TPSA: 222.30

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(S(=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: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 35 %
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
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(C#N)CC2)C(C)(C)C)cc1

 Ligand Name: Enzalutamide (analog)
SMILES: show
Cc1ccc(C(=O)N[C@H]2C(C)(C)[C@H](Oc3ccc(C#N)c(Cl)c3)C2(C)C)cc1

Calculated Values
MW: 1,136.86
Hbond donors: 4
Hbond acceptors: 12
cLogP: 8.35
TPSA: 221.09

SMILES: show
Cc1ncsc1-c1ccc([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](NC(=O)C2(C#N)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 100 %
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
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 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: 1,023.15
Hbond donors: 4
Hbond acceptors: 12
cLogP: 6.03
TPSA: 206.53

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: PEG
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 40 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 935.04
Hbond donors: 4
Hbond acceptors: 10
cLogP: 5.99
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 35 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,031.24
Hbond donors: 3
Hbond acceptors: 10
cLogP: 9.02
TPSA: 171.86

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCc2ccc(C#Cc3ccc(N4C(=S)N(c5ccc(C#N)c(C(F)(F)F)c5)C(=O)C4(C)C)cc3)cn2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 96 %
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
Calculated Values
MW: 1,033.23
Hbond donors: 4
Hbond acceptors: 10
cLogP: 8.72
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 88 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,005.17
Hbond donors: 4
Hbond acceptors: 10
cLogP: 7.94
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 65 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 949.07
Hbond donors: 4
Hbond acceptors: 10
cLogP: 6.38
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 33 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,073.28
Hbond donors: 3
Hbond acceptors: 12
cLogP: 7.43
TPSA: 178.34

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)C(C)(C)C)cc1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 80 %
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
Calculated Values
MW: 1,047.26
Hbond donors: 4
Hbond acceptors: 10
cLogP: 9.11
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
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
Comments: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 991.15
Hbond donors: 4
Hbond acceptors: 10
cLogP: 7.55
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 84 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,019.20
Hbond donors: 4
Hbond acceptors: 10
cLogP: 8.33
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 87 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,061.28
Hbond donors: 4
Hbond acceptors: 10
cLogP: 9.50
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 75 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 977.12
Hbond donors: 4
Hbond acceptors: 10
cLogP: 7.16
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 29 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 963.09
Hbond donors: 4
Hbond acceptors: 10
cLogP: 6.77
TPSA: 188.07

SMILES: show
Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)C(C)(C)C)cc1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 25 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
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: Enzalutamide (analog)
SMILES: show
Cc1ccc(N2C(=S)N(c3cnc(C#N)c(C(F)(F)F)c3)C(=O)C23CCC3)cc1

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

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(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: 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: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
SMILES: show
CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(-c2scnc2C)cc1)C(C)(C)C

 Ligand Name: Enzalutamide (analog)
SMILES: show
Cc1ccc(C(=O)N[C@H]2C(C)(C)[C@H](Oc3ccc(C#N)c(Cl)c3)C2(C)C)cc1

Calculated Values
MW: 1,085.81
Hbond donors: 4
Hbond acceptors: 11
cLogP: 8.07
TPSA: 197.30

SMILES: show
CC(=O)N[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)c1ccc(-c2scnc2C)cc1)C(C)(C)C

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: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
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: Enzalutamide (analog)
SMILES: show
Cc1ccc(C(=O)N[C@H]2C(C)(C)[C@H](Oc3ccc(C#N)c(Cl)c3)C2(C)C)cc1

Calculated Values
MW: 1,089.80
Hbond donors: 5
Hbond acceptors: 12
cLogP: 9.78
TPSA: 228.88

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](CC(=O)NCCCCCCCCCNC(=O)c2ccc(C(=O)N[C@H]3C(C)(C)[C@H](Oc4ccc(C#N)c(Cl)c4)C3(C)C)cc2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 96 %
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
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): 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: Daniel Zaidman
E3 ligase: VHL
E3 binder: Vh032 Analog
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: 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: 1,114.30
Hbond donors: 4
Hbond acceptors: 12
cLogP: 9.59
TPSA: 214.10

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](CC(=O)NCCCCCCCCCNC(=O)c2ccc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)cc2F)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 87 %
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: EC50 of ligand is LNCaP 25 nM, VCaP 87.4 nM, 22RV1 > 10 uM
Contributed by: Daniel Zaidman
Calculated Values
MW: 1,154.35
Hbond donors: 3
Hbond acceptors: 14
cLogP: 8.29
TPSA: 204.37

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](CC(=O)NCCCN2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 94 %
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
Calculated Values
MW: 1,097.26
Hbond donors: 2
Hbond acceptors: 13
cLogP: 8.31
TPSA: 192.34

SMILES: show
Cc1cc([C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](CC(=O)N2CCN(c3ccc(C#Cc4ccc(N5C(=S)N(c6ccc(C#N)c(C(F)(F)F)c6)C(=O)C5(C)C)cc4)cn3)CC2)c2ccc(-c3scnc3C)cc2)C(C)C)on1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 93 %
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
Calculated Values
MW: 1,102.32
Hbond donors: 2
Hbond acceptors: 12
cLogP: 8.93
TPSA: 179.45

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(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: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 97 %
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
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Enzalutamide (analog)
SMILES: show
Cc1ccc(C(=O)N[C@H]2C(C)(C)[C@H](Oc3ccc(C#N)c(Cl)c3)C2(C)C)cc1

Calculated Values
MW: 822.40
Hbond donors: 3
Hbond acceptors: 8
cLogP: 7.32
TPSA: 174.77

SMILES: show
CC1(C)[C@H](NC(=O)c2ccc(C(=O)NCCCCCCCCCCc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)cc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Linker type: Alkane
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 20 %
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
Calculated Values
MW: 829.40
Hbond donors: 2
Hbond acceptors: 9
cLogP: 5.96
TPSA: 152.15

SMILES: show
CC1(C)[C@H](NC(=O)c2ccc(C#CC3CCN(C4CCN(c5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)cc2)C(C)(C)[C@H]1Oc1ccc(C#N)c(Cl)c1

Linker type: Other
Incubation time (hours): 6
Cells: LNCaP
Dmax: = 25 %
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