PROTACpedia
A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol. 2018 Jan 18;25(1):88-99.e6. PMID:29129717 DOI:10.1016/j.chembiol.2017.10.005
Target: CDK12 Cyclin-dependent kinase 12 Q9NYV4 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK5RAP1 Mitochondrial tRNA methylthiotransferase CDK5RAP1 Q96SZ6 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: AURKB Aurora kinase B Q96GD4 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: aurka-a Aurora kinase A-A Q91820 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: MARK2 Serine/threonine-protein kinase MARK2 Q7KZI7 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: AAK1 AP2-associated protein kinase 1 Q2M2I8 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: PTK2B Protein-tyrosine kinase 2-beta Q14289 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK13 Cyclin-dependent kinase 13 Q14004 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: PRKAA1 5'-AMP-activated protein kinase catalytic subunit alpha-1 Q13131 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: ITK Tyrosine-protein kinase ITK/TSK Q08881 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: BTK Tyrosine-protein kinase BTK Q06187 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: Bosutinib
Ligand PDB Id: DB8
PDB with Ligand: 3UE4
IC50: = 1.2 nM
SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c(Cl)cc1Cl

Calculated Values
MW: 903.82
Hbond donors: 3
Hbond acceptors: 15
cLogP: 5.11
TPSA: 196.92

SMILES: show
COc1cc(Nc2c(C#N)cnc3cc(OCCCN4CCN(CCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)c(OC)cc23)c(Cl)cc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLM14, MV4-11
DC50: ~ 100 nM
Dmax: ~ 50 %
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: IC50 of ligand is inhibitory - data from Selleckchem. EC50 of the lidand is Src-dependent cell proliferation - data from Selleckchem.
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: RN486
Ligand PDB Id: 2V3
PDB with Ligand: 4OTR
IC50: < 4 nM
SMILES: show
CN1CCN(c2ccc(Nc3cc(-c4cccc(-n5ccc6cc(C7CC7)cc(F)c6c5=O)c4CO)cn(C)c3=O)nc2)CC1

Calculated Values
MW: 1,033.16
Hbond donors: 5
Hbond acceptors: 17
cLogP: 3.96
TPSA: 238.77

SMILES: show
Cc1cc(C2CC2)cc2ccn(-c3cccc(-c4cc(Nc5ccc(N6CCN(CCOCCOCCNC(=O)CNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)CC6)cn5)c(=O)n(C)c4)c3CO)c(=O)c12

Linker type: Other
Incubation time (hours): 4
Cells: MOLM14
DC50: < 40 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: IC50 of ligand is 4 nM (BTK inhibition)/ 0.3 nM (binding). EC50 of ligand is 20-30 nM (B-cell signaling).
Contributed by: Ronen Gabizon
Target: PTK2 Focal adhesion kinase 1 Q05397 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK17 Cyclin-dependent kinase 17 Q00537 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK6 Cyclin-dependent kinase 6 Q00534 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: LIMK2 LIM domain kinase 2 P53671 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: BLK Tyrosine-protein kinase Blk P51451 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK9 Cyclin-dependent kinase 9 P50750 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK7 Cyclin-dependent kinase 7 P50613 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: TEC Tyrosine-protein kinase Tec P42680 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: FLT3 Receptor-type tyrosine-protein kinase FLT3 P36888 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: AC220
Ligand PDB Id: P30
PDB with Ligand: 4XUF
IC50: < 1.6 nM
SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3ccccc34)cc2)no1

Calculated Values
MW: 1,004.14
Hbond donors: 5
Hbond acceptors: 17
cLogP: 4.80
TPSA: 243.31

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(CCOCCOCCNC(=O)CNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
DC50: < 10 nM
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; confirmed that AURKA, BTK and PTK2B are not degraded
Comments: Dmax is difficult to quantify because AC220 raises FLT3 expression levels. IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines. EC50 of PROTAC was measured on MOLM-14 cell lines.
Contributed by: Ronen Gabizon
Calculated Values
MW: 936.02
Hbond donors: 5
Hbond acceptors: 16
cLogP: 5.20
TPSA: 246.06

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCOCCOCCOCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)ccc34)cc2)no1

Linker type: PEG
Incubation time (hours): 12
Cells: MOLM14, MV4-11
DC50: < 10 nM
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; confirmed that AURKA, BTK and PTK2B are not degraded
Comments: Dmax is difficult to quantify because AC220 raises FLT3 expression levels. IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines. EC50 of PROTAC was measured on MOLM-14 cell lines.
Contributed by: Ronen Gabizon
Calculated Values
MW: 891.96
Hbond donors: 5
Hbond acceptors: 15
cLogP: 5.19
TPSA: 236.83

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCOCCOCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)ccc34)cc2)no1

Linker type: PEG
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
E3 ligase: Cereblon
E3 binder: Thalidomide
SMILES: show
O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

 Ligand Name: AC220
Ligand PDB Id: P30
PDB with Ligand: 4XUF
IC50: < 1.6 nM
SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3ccccc34)cc2)no1

Calculated Values
MW: 1,058.23
Hbond donors: 5
Hbond acceptors: 16
cLogP: 6.20
TPSA: 251.15

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(CC(=O)NCCCCCCCCNC(=O)COc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,134.28
Hbond donors: 5
Hbond acceptors: 19
cLogP: 4.68
TPSA: 278.84

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(CC(=O)NCCCOCCOCCOCCCNC(=O)COc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,176.32
Hbond donors: 5
Hbond acceptors: 19
cLogP: 4.99
TPSA: 295.91

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(C(=O)CCC(=O)NCCCOCCOCCOCCCNC(=O)COc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,100.27
Hbond donors: 5
Hbond acceptors: 16
cLogP: 6.50
TPSA: 268.22

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(C(=O)CCC(=O)NCCCCCCCCNC(=O)COc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,002.12
Hbond donors: 5
Hbond acceptors: 16
cLogP: 4.63
TPSA: 251.15

SMILES: show
CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCN(CC(=O)NCCCCNC(=O)COc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)CC5)ccc34)cc2)no1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Calculated Values
MW: 1,048.17
Hbond donors: 7
Hbond acceptors: 16
cLogP: 4.09
TPSA: 289.28

SMILES: show
CC(C)(C)/C(O)=C/C(=N)N[N+](=O)Nc1ccc(-c2cn3c(n2)sc2cc(OCCN4CCN(C(=O)CCC(=O)NCCCCNC(=O)COc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)ccc23)cc1

Linker type: Other
Incubation time (hours): 12
Cells: MOLM14, MV4-11
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: IC50 of ligand is 1.6 nM (binding); 1.1-4 (activity). EC50 of ligand is measured on MOLM-14 cell lines
Contributed by: Ronen Gabizon
Target: Btk Tyrosine-protein kinase BTK P35991 Mus musculus
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: WEE1 Wee1-like protein kinase P30291 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK2 Cyclin-dependent kinase 2 P24941 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: FER Tyrosine-protein kinase Fer P16591 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: CDK4 Cyclin-dependent kinase 4 P11802 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: FES Tyrosine-protein kinase Fes/Fps P07332 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: LCK Tyrosine-protein kinase Lck P06239 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: ULK1 Serine/threonine-protein kinase ULK1 O75385 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon
Target: GAK Cyclin-G-associated kinase O14976 Homo sapiens
E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show
Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

 Ligand Name: TL13-87
Ligand PDB Id: GUI
PDB with Ligand: 2XB7
IC50: < 1 uM
SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1Cl

Calculated Values
MW: 931.47
Hbond donors: 5
Hbond acceptors: 16
cLogP: 3.58
TPSA: 233.60

SMILES: show
CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCN(CCOCCOCCNC(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)ncc1Cl

Linker type: Other
Incubation time (hours): 4
Cells: MOLT-4, MOLM14
IC50: = 10.3 nM
DC50: < 100 nM
Dmax: > 85 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: No
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: Yes
Off-targets reported?: INCENP, NDUFAB1, CCNH, CCNK, and IKZF1
Comments: General kinase PROTAC, DCmax is for the most degraded kinase. IC50 of the ligand is for 193 kinases in the panel. IC50 of the PROTAC is by FLT3 kinase activity.
Contributed by: Ronen Gabizon