PROTACpedia
DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19;348(6241):1376-81. PMID:25999370 DOI:10.1126/science.aab1433
Target: FKBP1A Peptidyl-prolyl cis-trans isomerase FKBP1A P62942 Homo sapiens
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: SLF
SMILES: show
CCC(C)(C)C(=O)C(=O)N1CCCC[C@H]1C(=O)OC(CCc1ccc(OC)c(OC)c1)c1cccc(N)c1

Calculated Values
MW: 1,009.12
Hbond donors: 4
Hbond acceptors: 14
cLogP: 4.52
TPSA: 262.22

SMILES: show
CCC(C)(C)C(=O)C(=O)N1CCCC[C@H]1C(=O)OC(CCc1ccc(OC)c(OC)c1)c1cccc(NC(=O)CCC(=O)NCCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)c1

Linker type: Alkane
Incubation time (hours): 18
Cells: MV4;11, 293FT, 293FTCRBN−/−
DC50: = 10 nM
Dmax: = 50 %
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: Daniel Zaidman
Calculated Values
MW: 1,141.28
Hbond donors: 4
Hbond acceptors: 17
cLogP: 4.57
TPSA: 289.91

SMILES: show
CCC(C)(C)C(=O)C(=O)N1CCCC[C@H]1C(=O)OC(CCc1ccc(OC)c(OC)c1)c1cccc(NC(=O)CCC(=O)NCCCOCCOCCOCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)c1

Linker type: PEG
Incubation time (hours): 18
Cells: MV4;11, 293FT, 293FTCRBN−/−
DC50: < 10 nM
Dmax: = 60 %
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: Daniel Zaidman
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
IC50: = 28 nM
SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2

Calculated Values
MW: 785.28
Hbond donors: 3
Hbond acceptors: 12
cLogP: 3.68
TPSA: 194.05

SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCCCNC(=O)COc1cccc3c1C(=O)N(C1CCC(=O)NC1=O)C3=O)c1nnc(C)n1-2

Linker type: Alkane
Incubation time (hours): 1,2,4,8,16,24
Cells: MV4;11, SUM149, SUM159, MOLM13, MM1.SCRBN−/−, MM1.SW
IC50: = 20 nM
DC50: = 430 nM
Dmax: = 95 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: BRD2, BRD3, BRD4
Contributed by: Daniel Zaidman