PROTACpedia
Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds. J Med Chem. 2018 Jan 25;61(2):504-513. PMID:28595007 DOI:10.1021/acs.jmedchem.6b01912
Target: BRD3 Bromodomain-containing protein 3 Q15059 Homo sapiens
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: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(OC(C)(C)C)=O)C=C1

Calculated Values
MW: 1,002.66
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.60
TPSA: 211.49

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.1 μM
DC50: < 2.5 nM
Dmax: > 98 %
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: pEC50 for MV4;11 and HL60 cells: 7.57±0.03 and 6.66±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/8.6/7.0/7.4, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 98%/100%/100%/98%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 1,046.71
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.61
TPSA: 220.72

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.4 μM
DC50: < 4 nM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.91±0.04 and 5.90±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.4/8.0/6.5/6.7, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 99%/100%/99%/97%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 958.61
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.58
TPSA: 202.26

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 1 μM
DC50: < 0.1 μM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.75±0.03 and 5.84±0.06, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 7.0/7.0/6.5/6.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 96%/97%/97%/93%, respectively (HeLa cells).
Contributed by: Yangwode Jing
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: I-BET726
Ligand PDB Id: 73B
PDB with Ligand: 4BJX
SMILES: show
O=C(O)C1=CC=C(C2=CC3=C(N(C(C)=O)[C@@H](C)C[C@H]3NC4=CC=C(Cl)C=C4)C=C2)C=C1

Calculated Values
MW: 1,036.69
Hbond donors: 5
Hbond acceptors: 12
cLogP: 7.33
TPSA: 200.76

SMILES: show
O=C(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.1 μM
DC50: ~ 7.9 nM
Dmax: > 90 %
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: pEC50 for MV4;11 and HL60 cells: 7.31±0.03 and 6.57±0.02, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/7.6/7.3/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 98%/95%/91%/43%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 1,080.75
Hbond donors: 5
Hbond acceptors: 13
cLogP: 7.34
TPSA: 209.99

SMILES: show
O=C(NCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.25 μM
DC50: ~ 7.9 nM
Dmax: > 90 %
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: pEC50 for MV4;11 and HL60 cells: 7.08±0.05 and 6.37±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/7.5/7.7/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 95%/93%/92%/26%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 992.64
Hbond donors: 5
Hbond acceptors: 11
cLogP: 7.31
TPSA: 191.53

SMILES: show
O=C(NCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 1 μM
DC50: ~ 0.1 μM
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: pEC50 for MV4;11 and HL60 cells: 6.24±0.05 and 6.17±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 6.9/6.7/6.8/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 94%/78%/74%/37%, respectively (HeLa cells).
Contributed by: Yangwode Jing
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

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

Calculated Values
MW: 923.45
Hbond donors: 3
Hbond acceptors: 15
cLogP: 5.77
TPSA: 204.67

SMILES: show
CC1=NN=C2N1C3=C(C(C4=CC=C(C=C4)Cl)=N[C@H]2CC(NC5=CC=C(C=C5)OCCOCCOCCOCCNC6=C(C7=CC=C6)C(N(C7=O)C8CCC(NC8=O)=O)=O)=O)C(C)=C(C)S3

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 32 nM
DC50: < 1 nM
Dmax: > 83 %
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: pEC50 for MV4;11 and HL60 cells: 7.77±0.06 and 7.46±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 9.2/9.0/9.1/8.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 97%/100%/98%/83%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Target: BRD2 Bromodomain-containing protein 2 P25440 Homo sapiens
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: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(OC(C)(C)C)=O)C=C1

Calculated Values
MW: 1,002.66
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.60
TPSA: 211.49

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.1 μM
DC50: < 2.5 nM
Dmax: > 98 %
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: pEC50 for MV4;11 and HL60 cells: 7.57±0.03 and 6.66±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/8.6/7.0/7.4, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 98%/100%/100%/98%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 1,046.71
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.61
TPSA: 220.72

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.4 μM
DC50: < 4 nM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.91±0.04 and 5.90±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.4/8.0/6.5/6.7, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 99%/100%/99%/97%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 958.61
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.58
TPSA: 202.26

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 1 μM
DC50: < 0.1 μM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.75±0.03 and 5.84±0.06, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 7.0/7.0/6.5/6.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 96%/97%/97%/93%, respectively (HeLa cells).
Contributed by: Yangwode Jing
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

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

Calculated Values
MW: 923.45
Hbond donors: 3
Hbond acceptors: 15
cLogP: 5.77
TPSA: 204.67

SMILES: show
CC1=NN=C2N1C3=C(C(C4=CC=C(C=C4)Cl)=N[C@H]2CC(NC5=CC=C(C=C5)OCCOCCOCCOCCNC6=C(C7=CC=C6)C(N(C7=O)C8CCC(NC8=O)=O)=O)=O)C(C)=C(C)S3

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 32 nM
DC50: < 1 nM
Dmax: > 83 %
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: pEC50 for MV4;11 and HL60 cells: 7.77±0.06 and 7.46±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 9.2/9.0/9.1/8.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 97%/100%/98%/83%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
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: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(OC(C)(C)C)=O)C=C1

Calculated Values
MW: 1,002.66
Hbond donors: 4
Hbond acceptors: 15
cLogP: 5.60
TPSA: 211.49

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.1 μM
DC50: < 2.5 nM
Dmax: > 98 %
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: pEC50 for MV4;11 and HL60 cells: 7.57±0.03 and 6.66±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/8.6/7.0/7.4, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 98%/100%/100%/98%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 958.61
Hbond donors: 4
Hbond acceptors: 14
cLogP: 5.58
TPSA: 202.26

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 1 μM
DC50: < 0.1 μM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.75±0.03 and 5.84±0.06, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 7.0/7.0/6.5/6.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 96%/97%/97%/93%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 1,046.71
Hbond donors: 4
Hbond acceptors: 16
cLogP: 5.61
TPSA: 220.72

SMILES: show
ClC1=CC=C(C2=N[C@H](C3=NN=C(N3C4=C2C(C)=C(S4)C)C)CC(NCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](O)C5)C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)=O)=O)C=C1

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.4 μM
DC50: < 4 nM
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
Comments: pEC50 for MV4;11 and HL60 cells: 6.91±0.04 and 5.90±0.05, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.4/8.0/6.5/6.7, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 99%/100%/99%/97%, respectively (HeLa cells).
Contributed by: Yangwode Jing
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: I-BET726
Ligand PDB Id: 73B
PDB with Ligand: 4BJX
SMILES: show
O=C(O)C1=CC=C(C2=CC3=C(N(C(C)=O)[C@@H](C)C[C@H]3NC4=CC=C(Cl)C=C4)C=C2)C=C1

Calculated Values
MW: 1,036.69
Hbond donors: 5
Hbond acceptors: 12
cLogP: 7.33
TPSA: 200.76

SMILES: show
O=C(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.1 μM
DC50: ~ 7.9 nM
Dmax: > 90 %
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: pEC50 for MV4;11 and HL60 cells: 7.31±0.03 and 6.57±0.02, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/7.6/7.3/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 98%/95%/91%/43%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 1,080.75
Hbond donors: 5
Hbond acceptors: 13
cLogP: 7.34
TPSA: 209.99

SMILES: show
O=C(NCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 0.25 μM
DC50: ~ 7.9 nM
Dmax: > 90 %
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: pEC50 for MV4;11 and HL60 cells: 7.08±0.05 and 6.37±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 8.1/7.5/7.7/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 95%/93%/92%/26%, respectively (HeLa cells).
Contributed by: Yangwode Jing
Calculated Values
MW: 992.64
Hbond donors: 5
Hbond acceptors: 11
cLogP: 7.31
TPSA: 191.53

SMILES: show
O=C(NCCOCCOCC(N[C@@H](C(C)(C)C)C(N1[C@@H](C[C@@H](O)C1)C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)=O)=O)C4=CC=C(C5=CC6=C(N(C(C)=O)[C@@H](C)C[C@H]6NC7=CC=C(Cl)C=C7)C=C5)C=C4

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 1 μM
DC50: ~ 0.1 μM
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: pEC50 for MV4;11 and HL60 cells: 6.24±0.05 and 6.17±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 6.9/6.7/6.8/NA, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 94%/78%/74%/37%, respectively (HeLa cells).
Contributed by: Yangwode Jing
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

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

Calculated Values
MW: 923.45
Hbond donors: 3
Hbond acceptors: 15
cLogP: 5.77
TPSA: 204.67

SMILES: show
CC1=NN=C2N1C3=C(C(C4=CC=C(C=C4)Cl)=N[C@H]2CC(NC5=CC=C(C=C5)OCCOCCOCCOCCNC6=C(C7=CC=C6)C(N(C7=O)C8CCC(NC8=O)=O)=O)=O)C(C)=C(C)S3

Linker type: PEG
Incubation time (hours): 4, 24, 48
Cells: HeLa, HL60, MV4;11
EC50 (cells): ~ 32 nM
DC50: < 1 nM
Dmax: > 83 %
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: pEC50 for MV4;11 and HL60 cells: 7.77±0.06 and 7.46±0.03, respectively. pDC50 for Brd4 short/Brd4 long/Brd3/Brd2: 9.2/9.0/9.1/8.2, respectively (24h, HeLa cells). Dmax for Brd4 short/Brd4 long/Brd3/Brd2: 97%/100%/98%/83%, respectively (HeLa cells).
Contributed by: Yangwode Jing