lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(CCN4CCOCC4)C3)cc12
InChIKey: WBESJKBRCJONQX-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 424.52, ALogP 3.5, HBA 5, HBD 1, PSA 53.62, QED 0.66
Compound (SMILES): CCOC(=O)C1CC1CN[C@H]1CC[C@H](c2cc3c(-c4cc(F)ccc4OC)ccnc3[nH]2)CC1
InChIKey: DVVNHXOEAPZNNY-LWAMJLSBSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 465.57, ALogP 5.19, HBA 5, HBD 2, PSA 76.24, QED 0.45
Compound (SMILES): CN1CCC(c2cc3c(-c4nc(N)ccc4Cl)ccnc3[nH]2)CC1
InChIKey: NMOFSJVEPFAGLJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 341.85, ALogP 3.67, HBA 4, HBD 2, PSA 70.83, QED 0.75
Compound (SMILES): CN1CCC(c2cc3c(-c4nc(NCC5CCOCC5)ccc4Cl)ccnc3[nH]2)CC1
InChIKey: RZWWKCQREWTJSE-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 439.99, ALogP 4.93, HBA 5, HBD 2, PSA 66.07, QED 0.59
Compound (SMILES): c1ccc(CCNc2cccc(-c3ccnc4[nH]c(C5CCNCC5)cc34)n2)cc1
InChIKey: SOUOCRDJFLDYDD-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 397.53, ALogP 4.75, HBA 4, HBD 3, PSA 65.63, QED 0.44
Compound (SMILES): O=C1CCCN1CCNc1cccc(-c2ccnc3[nH]c(C4CCNCC4)cc23)n1
InChIKey: WHXJBIWHSJCFCG-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 404.52, ALogP 3.13, HBA 5, HBD 3, PSA 85.94, QED 0.59
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(CC(O)CO)CC3)cc12
InChIKey: AOMPRQWVOKOUKJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 399.47, ALogP 2.91, HBA 5, HBD 3, PSA 81.61, QED 0.59
Compound (SMILES): CN1CCC(c2cc3c(-c4nc(NCc5ccncc5)ccc4Cl)ccnc3[nH]2)CC1
InChIKey: JSJOGCJKTLAUML-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 432.96, ALogP 5.09, HBA 5, HBD 2, PSA 69.73, QED 0.46
Compound (SMILES): CN1CCC(c2cc3c(-c4cccc(NCCO)n4)ccnc3[nH]2)CC1
InChIKey: RRYYSXNCESRHDH-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 351.45, ALogP 2.84, HBA 5, HBD 3, PSA 77.07, QED 0.66
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3(O)CCOCC3)cc12
InChIKey: VLALFVOYKRZFDF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 342.37, ALogP 3.38, HBA 4, HBD 2, PSA 67.37, QED 0.77
Compound (SMILES): CN1CCC(c2cc3c(-c4nc(NCC5CCN(C(=O)OC(C)(C)C)C5)ccc4Cl)ccnc3[nH]2)CC1
InChIKey: BTFNSJFKHYPZFL-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 525.1, ALogP 5.76, HBA 6, HBD 2, PSA 86.38, QED 0.44
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(C(=O)CNC4CCC(O)CC4)CC3)cc12
InChIKey: MFMGZBUGOSVXOS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 480.58, ALogP 3.98, HBA 5, HBD 3, PSA 90.48, QED 0.5
Compound (SMILES): Nc1ccc(F)c(-c2ccnc3[nH]c(C4CCNCC4)cc23)c1
InChIKey: RHHQNSIWSWQQJF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 310.38, ALogP 3.42, HBA 3, HBD 3, PSA 66.73, QED 0.64
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCCCNC3)cc12
InChIKey: CQLIGLBBNRBZMC-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 339.41, ALogP 4.23, HBA 3, HBD 2, PSA 49.94, QED 0.75
Compound (SMILES): F[C@@H]1CN[C@H](CNc2ccc(Cl)c(-c3ccnc4[nH]c(C5CCNCC5)cc34)n2)C1
InChIKey: MQANNSLVFICJTQ-GJZGRUSLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 428.94, ALogP 3.86, HBA 5, HBD 4, PSA 77.66, QED 0.5
Compound (SMILES): Fc1ccc(NCc2ccccc2)cc1-c1ccnc2[nH]c(C3CCCNC3)cc12
InChIKey: MPHFYYSKXDMJBP-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 400.5, ALogP 5.45, HBA 3, HBD 3, PSA 52.74, QED 0.42
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(S(N)(=O)=O)CC3)cc12
InChIKey: XFUXKSYIUVHEHS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 402.45, ALogP 2.67, HBA 4, HBD 2, PSA 101.31, QED 0.7
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(N)=O)CC3)cc12
InChIKey: HIRDTWFIJMZJPT-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 380.42, ALogP 2.95, HBA 4, HBD 2, PSA 84.24, QED 0.71
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(=O)N4CCC[C@H]4CO)CC3)cc12
InChIKey: JLTPEPZBLJDIDW-IBGZPJMESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 464.54, ALogP 3.45, HBA 5, HBD 2, PSA 81.69, QED 0.58
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCC(N[C@@H](C(=O)O)C(C)C)CC3)cc12
InChIKey: VKEWATIKYFEHIF-IRCUZVAFSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 437.52, ALogP 5.01, HBA 4, HBD 3, PSA 87.24, QED 0.48
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(CC(N)=O)CC3)cc12
InChIKey: APWXCXQXZHUHNP-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 382.44, ALogP 3.04, HBA 4, HBD 2, PSA 84.24, QED 0.71
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(CC(=O)N4CCC[C@H]4CO)CC3)cc12
InChIKey: VUFDXMUYPNFGNC-IBGZPJMESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 466.56, ALogP 3.54, HBA 5, HBD 2, PSA 81.69, QED 0.58
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3CCN(CC(=O)N4CC(O)C4)CC3)cc12
InChIKey: FDOWFKPWAZQJGE-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 456.49, ALogP 2.9, HBA 5, HBD 2, PSA 81.69, QED 0.62
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN(CC(=O)N4CC(O)C4)CC3)c(C#N)c12
InChIKey: DIMWAZPRSFTYDZ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 479.49, ALogP 2.68, HBA 6, HBD 2, PSA 105.48, QED 0.58
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(=O)N(C)C)C(C)(C)C3)cc12
InChIKey: ZWVAYSKSSFNSIF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 436.53, ALogP 4.33, HBA 4, HBD 1, PSA 61.46, QED 0.65
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CC4CN(S(C)(=O)=O)CC4C3)cc12
InChIKey: BYWUYRYQHZYENJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 445.49, ALogP 3.81, HBA 4, HBD 1, PSA 75.29, QED 0.66
Compound (SMILES): COc1ccc(F)cc1-c1c(C#N)cnc2[nH]c(C3CCN(CC(=O)N4CCC[C@H]4CO)CC3)cc12
InChIKey: LKRMXRXVKMFHRU-FQEVSTJZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 491.57, ALogP 3.41, HBA 6, HBD 2, PSA 105.48, QED 0.55
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CC4CN(CC(=O)N5CC(O)C5)CC4C3)cc12
InChIKey: XJAQHVGZOWIIMV-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 480.52, ALogP 3.05, HBA 5, HBD 2, PSA 81.69, QED 0.59
Compound (SMILES): CCCCn1c(N)c(S(=O)(=O)c2ccccc2)c2nc3ccccc3nc21
InChIKey: XBBNNPJLYYTUSV-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 = 64000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 380.47, ALogP 3.8, HBA 6, HBD 1, PSA 90.87, QED 0.57
Compound (SMILES): CCCCn1c(NC(=O)c2ccccc2)c(S(=O)(=O)c2ccccc2)c2nc3ccccc3nc21
InChIKey: FITWGNRMVRVCPA-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 = 98000 nM (pChEMBL 4.010000228881836)
Descriptors: MW 484.58, ALogP 5.47, HBA 6, HBD 1, PSA 93.95, QED 0.33
Compound (SMILES): CCCCn1c(NC(=O)c2ccc(Cl)cc2)c(C#N)c2nc3cc(C)c(C)cc3nc21
InChIKey: PWZRVJMRGOZDAF-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 431.93, ALogP 5.78, HBA 5, HBD 1, PSA 83.6, QED 0.43
Compound (SMILES): CCCCNC(=O)c1c(NC(=O)c2ccccc2Cl)n(Cc2ccccc2)c2nc3ccccc3nc12
InChIKey: MIUCMOZNCFLCTF-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 512.01, ALogP 6.07, HBA 5, HBD 2, PSA 88.91, QED 0.25
Compound (SMILES): CCCCn1c(NC(=O)c2ccco2)c(C#N)c2nc3ccccc3nc21
InChIKey: KMEZFETVEYLRBC-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 359.39, ALogP 4.1, HBA 6, HBD 1, PSA 96.74, QED 0.58
Compound (SMILES): CCCCn1c(NC(=O)c2ccccc2Cl)c(S(=O)(=O)c2ccccc2)c2nc3ccccc3nc21
InChIKey: XVPIUSJLECVGGX-UHFFFAOYSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Biochemical Assay: Through the Molecular Library Probe Production Center Network (MLPCN), at least 300,000 compounds were screened using a TR-FRET method, an ALPHASCREEN method or both, and tested for their ability to inhibit SUMOylation of a target protein via SUMO E1 or SUMO E2. The assays were based on SUMOylation of the target protein RanGAP1, which is a protein that is efficiently SUMOylated with only the SUMO E1 and E2 enzymes, and does not use E3 ligases. A fluorescence resonance energy transfer (FRET) assay was the primary assay followed by a chemoluminescence-based secondary assay using ALPHA screen to eliminate false positive hits. Then, the hits were screened by a poly-ubiquitination assay using ubiquitin, ubiquitin E1, Ubc5 and Apc11 to eliminate inhibitors not specific to SUMOylation. The screening identified a potent family of SUMOylation inhibitors based on a tricyclic scaffold.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 519.03, ALogP 6.12, HBA 6, HBD 1, PSA 93.95, QED 0.28
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ccc(NCc2c(F)ccc(F)c2F)nc1
InChIKey: GLURMROUHGYRED-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 386.3, ALogP 4.53, HBA 4, HBD 1, PSA 42.74, QED 0.53
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ccc(NCc2ccc(F)cc2F)nc1
InChIKey: DTQCPVMYKXVJRV-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 368.31, ALogP 4.39, HBA 4, HBD 1, PSA 42.74, QED 0.69
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ccc(NCc2c(F)cc(F)cc2F)nc1
InChIKey: RLYFWFGERVZBGJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 386.3, ALogP 4.53, HBA 4, HBD 1, PSA 42.74, QED 0.67
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ccc(NCc2c(F)cncc2F)nc1
InChIKey: DQSWFCKIRZAYPZ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 369.3, ALogP 3.79, HBA 5, HBD 1, PSA 55.63, QED 0.71
Compound (SMILES): Cc1cccc(F)c1CNc1ccc(-c2cc(C(F)(F)F)nn2C)cn1
InChIKey: YCLZESJJLPHDMB-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 364.35, ALogP 4.56, HBA 4, HBD 1, PSA 42.74, QED 0.69
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1cnc(NCc2ccccc2F)nc1
InChIKey: WCLROHKKQYMCOA-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 351.31, ALogP 3.65, HBA 5, HBD 1, PSA 55.63, QED 0.73
Compound (SMILES): Fc1cccc(F)c1CNc1ccc(-n2nc(C(F)(F)F)cc2C(F)(F)F)cn1
InChIKey: DWSTXONOVMIFSC-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 422.28, ALogP 5.2, HBA 4, HBD 1, PSA 42.74, QED 0.59
Compound (SMILES): Fc1cc(F)c(CNc2ccc(-n3nc(C(F)(F)F)cc3C(F)(F)F)cn2)c(F)c1
InChIKey: YJQZXLGMJDQQKZ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 440.27, ALogP 5.33, HBA 4, HBD 1, PSA 42.74, QED 0.56
Compound (SMILES): Cc1nc(C(F)(F)F)cn1-c1ccc(NCc2c(F)cccc2F)nc1
InChIKey: QAWJFNWFRINMMU-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of human Orai1/STIM1 expressed in HEK293 cells assessed as intracellular calcium level after 30 mins by FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 368.31, ALogP 4.48, HBA 4, HBD 1, PSA 42.74, QED 0.69