Target: CDK6 Cyclin-dependent kinase 6 Q00534 Homo sapiens

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: Abemaciclib
Ligand PDB Id: 6ZZ
PDB with Ligand: 5L2S
SMILES: show

CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1

PROTAC (Active) name: CP-A2 - status:Reviewed Edit

Calculated Values
MW: 932.99
Hbond donors: 3
Hbond acceptors: 18
cLogP: 4.26
TPSA: 219.75

SMILES: show

Cc1nc2c(F)cc(-c3nc(Nc4ccc(CN5CCN(c6cn(CCOCCOCCNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)nn6)CC5)cn4)ncc3F)cc2n1C(C)C

Linker type: Other
DC₅₀: = 129.7 nM
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: DC50 for CDK4 > 500 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-A3 - status:Reviewed Edit

Calculated Values
MW: 977.05
Hbond donors: 3
Hbond acceptors: 19
cLogP: 4.28
TPSA: 228.98

SMILES: show

Cc1nc2c(F)cc(-c3nc(Nc4ccc(CN5CCN(c6cn(CCOCCOCCOCCNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)nn6)CC5)cn4)ncc3F)cc2n1C(C)C

Linker type: Other
DC₅₀: = 271.9 nM
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: DC50 for CDK4 > 500 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-A1 - status:Reviewed Edit

Calculated Values
MW: 888.94
Hbond donors: 3
Hbond acceptors: 17
cLogP: 4.24
TPSA: 210.52

SMILES: show

Cc1nc2c(F)cc(-c3nc(Nc4ccc(CN5CCN(c6cn(CCOCCNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)nn6)CC5)cn4)ncc3F)cc2n1C(C)C

Linker type: Other
DC₅₀: = 8.6 nM
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: DC50 for CDK4 > 500 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-A4 - status:Reviewed Edit

Calculated Values
MW: 1,021.10
Hbond donors: 3
Hbond acceptors: 20
cLogP: 4.29
TPSA: 238.21

SMILES: show

Cc1nc2c(F)cc(-c3nc(Nc4ccc(CN5CCN(c6cn(CCOCCOCCOCCOCCNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)nn6)CC5)cn4)ncc3F)cc2n1C(C)C

Linker type: Other
DC₅₀: = 145.5 nM
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: DC50 for CDK4 > 500 nM

Contributed by: Efrat Resnick

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Lenalidomide
SMILES: show

Nc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

PROTAC (Active) name: CP-16 - status:Reviewed Edit

Calculated Values
MW: 855.02
Hbond donors: 2
Hbond acceptors: 15
cLogP: 5.03
TPSA: 193.44

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCCCCCc6cccc7c6CN(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 1.7 nM
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: DC50 for CDK4 > 50 nM

Contributed by: Efrat Resnick

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

Representative PROTAC (Active) name: CP-10 - status:Reviewed Edit

Calculated Values
MW: 871.96
Hbond donors: 3
Hbond acceptors: 18
cLogP: 3.00
TPSA: 231.77

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
Cells: U251
DC₅₀: = 2.1 nM
D_max: = 89 %
Tested a non-binding E3 control?: Yes
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: No

Comments: DC50 for CDK4 > 100 nM. EC50 of PROTAC is 10nM in MM.lS 8nM in Mino.

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-14 - status:Reviewed Edit

Calculated Values
MW: 884.01
Hbond donors: 3
Hbond acceptors: 17
cLogP: 4.54
TPSA: 222.54

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCCCCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 10.6 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-13 - status:Reviewed Edit

Calculated Values
MW: 869.99
Hbond donors: 3
Hbond acceptors: 17
cLogP: 4.15
TPSA: 222.54

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCCCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 5.3 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-5 - status:Reviewed Edit

Calculated Values
MW: 847.93
Hbond donors: 4
Hbond acceptors: 16
cLogP: 2.32
TPSA: 230.16

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 1.1 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-22 - status:Reviewed Edit

Calculated Values
MW: 878.99
Hbond donors: 2
Hbond acceptors: 16
cLogP: 4.48
TPSA: 210.51

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCCCCC#Cc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 86.8 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-3 - status:Reviewed Edit

Calculated Values
MW: 960.07
Hbond donors: 3
Hbond acceptors: 20
cLogP: 3.03
TPSA: 250.23

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
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: Efrat Resnick

PROTAC (Active) name: CP-21 - status:Reviewed Edit

Calculated Values
MW: 864.97
Hbond donors: 2
Hbond acceptors: 16
cLogP: 4.09
TPSA: 210.51

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCCCC#Cc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 81.6 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-15 - status:Reviewed Edit

Calculated Values
MW: 834.93
Hbond donors: 3
Hbond acceptors: 16
cLogP: 3.22
TPSA: 210.29

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 1.6 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-8 - status:Reviewed Edit

Calculated Values
MW: 980.09
Hbond donors: 4
Hbond acceptors: 19
cLogP: 2.37
TPSA: 257.85

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 31 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-4 - status:Reviewed Edit

Calculated Values
MW: 1,004.12
Hbond donors: 3
Hbond acceptors: 21
cLogP: 3.05
TPSA: 259.46

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Contributed by: Efrat Resnick

PROTAC (Active) name: CP-2 - status:Reviewed Edit

Calculated Values
MW: 916.01
Hbond donors: 3
Hbond acceptors: 19
cLogP: 3.02
TPSA: 241.00

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
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: Efrat Resnick

PROTAC (Active) name: CP-6 - status:Reviewed Edit

Calculated Values
MW: 891.99
Hbond donors: 4
Hbond acceptors: 17
cLogP: 2.34
TPSA: 239.39

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Linker type: Other
DC₅₀: = 24.2 nM
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: DC50 for CDK4 > 100 nM

Contributed by: Efrat Resnick

E3 Ligand Binder

E3 ligase: Mdm2
E3 binder: Nutlin-3b
SMILES: show

COc1ccc(C2=N[C@H](c3ccc(Cl)cc3)[C@H](c3ccc(Cl)cc3)N2C(=O)N2CCNC(=O)C2)c(OC(C)C)c1

Ligand

Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

PROTAC (Inactive) name: MP-2 - status:Reviewed Edit

Calculated Values
MW: 1,281.32
Hbond donors: 2
Hbond acceptors: 20
cLogP: 8.23
TPSA: 249.20

SMILES: show

COc1ccc(C2=N[C@H](c3ccc(Cl)cc3)[C@H](c3ccc(Cl)cc3)N2C(=O)N2CCN(CC(=O)NCCOCCOCCn3cc(CN4CCN(c5ccc(Nc6ncc7c(C)c(C(C)=O)c(=O)n(C8CCCC8)c7n6)nc5)CC4)nn3)C(=O)C2)c(OC(C)C)c1

Contributed by: Efrat Resnick

PROTAC (Inactive) name: MP-3 - status:Reviewed Edit

Calculated Values
MW: 1,325.37
Hbond donors: 2
Hbond acceptors: 21
cLogP: 8.25
TPSA: 258.43

SMILES: show

COc1ccc(C2=N[C@H](c3ccc(Cl)cc3)[C@H](c3ccc(Cl)cc3)N2C(=O)N2CCN(CC(=O)NCCOCCOCCOCCn3cc(CN4CCN(c5ccc(Nc6ncc7c(C)c(C(C)=O)c(=O)n(C8CCCC8)c7n6)nc5)CC4)nn3)C(=O)C2)c(OC(C)C)c1

Contributed by: Efrat Resnick

PROTAC (Inactive) name: MP-1 - status:Reviewed Edit

Calculated Values
MW: 1,237.26
Hbond donors: 2
Hbond acceptors: 19
cLogP: 8.21
TPSA: 239.97

SMILES: show

COc1ccc(C2=N[C@H](c3ccc(Cl)cc3)[C@H](c3ccc(Cl)cc3)N2C(=O)N2CCN(CC(=O)NCCOCCn3cc(CN4CCN(c5ccc(Nc6ncc7c(C)c(C(C)=O)c(=O)n(C8CCCC8)c7n6)nc5)CC4)nn3)C(=O)C2)c(OC(C)C)c1

Contributed by: Efrat Resnick

E3 Ligand Binder

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

Ligand Name: Palbociclib
Ligand PDB Id: LQQ
PDB with Ligand: 5L2I
SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O

PROTAC (Inactive) name: VP-4 - status:Reviewed Edit

Calculated Values
MW: 1,260.53
Hbond donors: 5
Hbond acceptors: 23
cLogP: 4.67
TPSA: 304.61

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCOCCOCCNC(=O)CCC(=O)NC(C(=O)N6C[C@H](O)C[C@H]6C(=O)NCc6ccc(-c7scnc7C)cc6)C(C)(C)C)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Contributed by: Efrat Resnick

PROTAC (Inactive) name: VP-1 - status:Reviewed Edit

Calculated Values
MW: 1,128.37
Hbond donors: 5
Hbond acceptors: 20
cLogP: 4.62
TPSA: 276.92

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCNC(=O)CCC(=O)NC(C(=O)N6C[C@H](O)C[C@H]6C(=O)NCc6ccc(-c7scnc7C)cc6)C(C)(C)C)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Contributed by: Efrat Resnick

PROTAC (Inactive) name: VP-2 - status:Reviewed Edit

Calculated Values
MW: 1,172.43
Hbond donors: 5
Hbond acceptors: 21
cLogP: 4.64
TPSA: 286.15

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCNC(=O)CCC(=O)NC(C(=O)N6C[C@H](O)C[C@H]6C(=O)NCc6ccc(-c7scnc7C)cc6)C(C)(C)C)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Contributed by: Efrat Resnick

PROTAC (Inactive) name: VP-3 - status:Reviewed Edit

Calculated Values
MW: 1,216.48
Hbond donors: 5
Hbond acceptors: 22
cLogP: 4.66
TPSA: 295.38

SMILES: show

CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCOCCNC(=O)CCC(=O)NC(C(=O)N6C[C@H](O)C[C@H]6C(=O)NCc6ccc(-c7scnc7C)cc6)C(C)(C)C)nn5)CC4)cn3)nc2n(C2CCCC2)c1=O

Contributed by: Efrat Resnick

E3 Ligand Binder

E3 ligase: Cereblon
E3 binder: Pomalidomide
SMILES: show

Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Ligand

Ligand Name: ribociclib
Ligand PDB Id: 6ZZ
PDB with Ligand: 5L2T
SMILES: show

CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1

PROTAC (Inactive) name: CP-R3 - status:Reviewed Edit

Calculated Values
MW: 947.07
Hbond donors: 3
Hbond acceptors: 19
cLogP: 2.86
TPSA: 236.40

SMILES: show

CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n1C1CCCC1

Contributed by: Efrat Resnick

PROTAC (Inactive) name: CP-R1 - status:Reviewed Edit

Calculated Values
MW: 858.96
Hbond donors: 3
Hbond acceptors: 17
cLogP: 2.83
TPSA: 217.94

SMILES: show

CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n1C1CCCC1

Contributed by: Efrat Resnick

PROTAC (Inactive) name: CP-R2 - status:Reviewed Edit

Calculated Values
MW: 903.02
Hbond donors: 3
Hbond acceptors: 18
cLogP: 2.85
TPSA: 227.17

SMILES: show

CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(Cc5cn(CCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)nc2n1C1CCCC1

Contributed by: Efrat Resnick