PROTACpedia
Design, synthesis and biological evaluation of nuclear receptor-degradation inducers. Bioorg Med Chem. 2011 Nov 15;19(22):6768-78. PMID:22014751 DOI:10.1016/j.bmc.2011.09.041
Target: RARA Retinoic acid receptor alpha P10276 Homo sapiens
E3 ligase: cIAP1
E3 binder: BE04
SMILES: show
N[C@@H]([C@@H](C(N[C@H](C(NC)=O)CC(C)C)=O)O)CC1=CC=CC=C1

 Ligand Name: Ch55
Ligand PDB Id: EQN
PDB with Ligand: 3KMR
SMILES: show
CC(C)(C1=CC(C(/C=C/C(C=C2)=CC=C2C(O)=O)=O)=CC(C(C)(C)C)=C1)C

Calculated Values
MW: 917.15
Hbond donors: 6
Hbond acceptors: 11
cLogP: 5.39
TPSA: 224.84

SMILES: show
O=C(O)C1=CC=C(/C=C/C(C2=CC(C(C)(C)C)=CC(C(C)(C)C)=C2)=O)C=C1OCCCNC(COCCOCCOCCNC([C@@H](NC([C@@H](O)[C@H](N)CC3=CC=CC=C3)=O)CC(C)C)=O)=O

Linker type: PEG
Incubation time (hours): 6, 24
Cells: HT1080
DC50: ~ 10 μM
Dmax: ~ 90 %
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: The PDB ligand ID is for Am80
Contributed by: Yangwode Jing, Ronen Gabizon
Target: AR Androgen receptor P10275 Homo sapiens
E3 ligase: cIAP1
E3 binder: BE04
SMILES: show
N[C@@H]([C@@H](C(N[C@H](C(NC)=O)CC(C)C)=O)O)CC1=CC=CC=C1

 Ligand Name: DHT
Ligand PDB Id: DHT
PDB with Ligand: 1T5Z
SMILES: show
O[C@H]1CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])CC(CC[C@]4(C)[C@@]3([H])CC[C@]12C)=O

Calculated Values
MW: 770.02
Hbond donors: 4
Hbond acceptors: 10
cLogP: 4.14
TPSA: 175.51

SMILES: show
O=C(O[C@H]1CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])CC(CC[C@]4(C)[C@@]3([H])CC[C@]12C)=O)COCCOCCOCCNC([C@H](CC(C)C)NC([C@@H](O)[C@H](N)CC5=CC=CC=C5)=O)=O

Linker type: PEG
Incubation time (hours): 24
Cells: MCF-7
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: Yangwode Jing
Target: ESR1 Estrogen receptor P03372 Homo sapiens
E3 ligase: cIAP1
E3 binder: BE04
SMILES: show
N[C@@H]([C@@H](C(N[C@H](C(NC)=O)CC(C)C)=O)O)CC1=CC=CC=C1

 Ligand Name: Estrone
SMILES: show
OC(C=C1)=CC(CC[C@@]2([H])[C@]3([H])CC4)=C1[C@@]2([H])CC[C@]3(C)C4=O

Calculated Values
MW: 763.98
Hbond donors: 6
Hbond acceptors: 10
cLogP: 3.35
TPSA: 193.83

SMILES: show
CC(C)C[C@H](NC([C@@H](O)[C@H](N)CC1=CC=CC=C1)=O)C(NCCOCCOCCNC(CO/N=C2CC[C@@]3([H])[C@]4([H])CCC5=CC(O)=CC=C5[C@@]4([H])CC[C@]\23C)=O)=O

Linker type: PEG
Incubation time (hours): 24
Cells: MCF-7
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: No
Proteomics data available?: No
Tested engagement in cells?: No
Off-targets reported?: No
Contributed by: Yangwode Jing