PROTACpedia
Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression. J Med Chem. 2018 Aug 9;61(15):6685-6704. PMID:30019901 DOI:10.1021/acs.jmedchem.8b00506
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: QCA276
IC50: = 10.7 nM
SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(C)c3)c(Cc3ccccc3)c1COC2

Calculated Values
MW: 695.81
Hbond donors: 1
Hbond acceptors: 10
cLogP: 4.45
TPSA: 124.24

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(CCCC#Cc4cccc5c4CN(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Other
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
DC50: < 0.5 nM
Dmax: = 100 %
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 0.0083nM-0.062nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 728.84
Hbond donors: 2
Hbond acceptors: 12
cLogP: 4.54
TPSA: 153.34

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(CCCCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Alkane
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 0.02nM-0.19nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 686.75
Hbond donors: 2
Hbond acceptors: 12
cLogP: 3.37
TPSA: 153.34

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(CCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Alkane
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 0.379nM-2.23nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 714.81
Hbond donors: 2
Hbond acceptors: 12
cLogP: 4.15
TPSA: 153.34

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(CCCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Alkane
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 0.02nM-0.19nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 673.71
Hbond donors: 1
Hbond acceptors: 12
cLogP: 3.29
TPSA: 150.54

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(COc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: PEG
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 19.7nM-311nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 700.78
Hbond donors: 2
Hbond acceptors: 12
cLogP: 3.76
TPSA: 153.34

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(CCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Alkane
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of PROTAC is 0.038nM-0.56nM. EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman
Calculated Values
MW: 643.69
Hbond donors: 1
Hbond acceptors: 11
cLogP: 3.24
TPSA: 141.31

SMILES: show
Cc1nnc2n1-c1sc(C#Cc3cnn(-c4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)c3)c(Cc3ccccc3)c1COC2

Linker type: Other
Incubation time (hours): 3,24,96
Cells: RS4;11, MV4;11, MOLM-13,
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?: BRD2, BRD3
Comments: EC50 of ligand is 55.8-207 nM.
Contributed by: Daniel Zaidman