lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC[C@H]1CC[C@@H](N2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)CC1
InChIKey: HTKJTEKPUISRBJ-WOVMCDHWSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 385.51, ALogP 2.41, HBA 4, HBD 1, PSA 75.87, QED 0.84
Compound (SMILES): COC[C@H]1CC[C@H](N2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)CC1
InChIKey: HTKJTEKPUISRBJ-JCNLHEQBSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 385.51, ALogP 2.41, HBA 4, HBD 1, PSA 75.87, QED 0.84
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc(F)cc3)CC1)C2
InChIKey: PNGLNUUGIVGKKR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 367.42, ALogP 2.55, HBA 3, HBD 1, PSA 66.64, QED 0.9
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccccc3F)CC1)C2
InChIKey: NTRIZHVBBWQPSL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 367.42, ALogP 2.55, HBA 3, HBD 1, PSA 66.64, QED 0.9
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccc(F)c3)CC1)C2
InChIKey: DIXQEUSVVHCYGR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 367.42, ALogP 2.55, HBA 3, HBD 1, PSA 66.64, QED 0.9
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc4ccccc4n3)CC1)C2
InChIKey: XGXIIPOUWCBAEN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 400.48, ALogP 2.95, HBA 4, HBD 1, PSA 79.53, QED 0.73
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc(F)cc3F)CC1)C2
InChIKey: KCTRCOAVSQQBQD-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 385.41, ALogP 2.68, HBA 3, HBD 1, PSA 66.64, QED 0.88
Compound (SMILES): Cc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1C
InChIKey: IKRIJRYFPIMBDP-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 377.49, ALogP 3.02, HBA 3, HBD 1, PSA 66.64, QED 0.89
Compound (SMILES): Cc1ncsc1CN1CCC(N2Cc3cccc(C(N)=O)c3C2=O)CC1
InChIKey: WJWLTLAIHKFPCH-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 370.48, ALogP 2.17, HBA 5, HBD 1, PSA 79.53, QED 0.89
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(CC3CCN(Cc4ccccc4)CC3)CC1)C2
InChIKey: FGQGCELCWNWLFN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 446.6, ALogP 3.12, HBA 4, HBD 1, PSA 69.88, QED 0.74
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc4cc[nH]c4c3)CC1)C2
InChIKey: XAHBYWOQGRBOKX-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 388.47, ALogP 2.89, HBA 3, HBD 2, PSA 82.43, QED 0.72
Compound (SMILES): CC(C)n1cc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)c2ccccc21
InChIKey: SRQRRBLLTSGSRF-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 430.55, ALogP 3.94, HBA 4, HBD 1, PSA 71.57, QED 0.67
Compound (SMILES): Cn1cc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cn1
InChIKey: OMHQMCRXZBMOFQ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 353.43, ALogP 1.14, HBA 5, HBD 1, PSA 84.46, QED 0.89
Compound (SMILES): Cc1c(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cnn1C
InChIKey: RMUOIWTVOGZFPR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 367.45, ALogP 1.45, HBA 5, HBD 1, PSA 84.46, QED 0.89
Compound (SMILES): COc1cccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)c1
InChIKey: HOUBLQHUJDBMLG-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 379.46, ALogP 2.41, HBA 4, HBD 1, PSA 75.87, QED 0.87
Compound (SMILES): Cc1ccsc1CN1CCC(N2Cc3cccc(C(N)=O)c3C2=O)CC1
InChIKey: NWCBQNVGTYZIMG-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 369.49, ALogP 2.78, HBA 4, HBD 1, PSA 66.64, QED 0.9
Compound (SMILES): CCCOc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: BRYKCYDBAKXODO-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 407.51, ALogP 3.19, HBA 4, HBD 1, PSA 75.87, QED 0.76
Compound (SMILES): CC(C)c1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: CJCYOWMNIFJTIR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 391.52, ALogP 3.53, HBA 3, HBD 1, PSA 66.64, QED 0.85
Compound (SMILES): COc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: JGDZCUDTQHFFIB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 379.46, ALogP 2.41, HBA 4, HBD 1, PSA 75.87, QED 0.87
Compound (SMILES): CCOc1cccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)c1
InChIKey: MXSZWVMTWCTPEC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 393.49, ALogP 2.8, HBA 4, HBD 1, PSA 75.87, QED 0.82
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccc(Cl)c3)CC1)C2
InChIKey: WVPKSLQDOPLTLR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 383.88, ALogP 3.06, HBA 3, HBD 1, PSA 66.64, QED 0.88
Compound (SMILES): CCc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: XZQCTFIYSCYMLY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 377.49, ALogP 2.97, HBA 3, HBD 1, PSA 66.64, QED 0.87
Compound (SMILES): CC(C)Oc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: VTOJWYHGKOAOBI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 407.51, ALogP 3.19, HBA 4, HBD 1, PSA 75.87, QED 0.8
Compound (SMILES): Cc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)s1
InChIKey: OKRJSUCETUOTEB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 369.49, ALogP 2.78, HBA 4, HBD 1, PSA 66.64, QED 0.9
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(CC1CCN(Cc3ccc(F)cc3)CC1)C2
InChIKey: NUHXDBWKUCTWQB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 381.45, ALogP 2.79, HBA 3, HBD 1, PSA 66.64, QED 0.87
Compound (SMILES): NC(=O)c1cc(F)cc2c1C(=O)N(C1CCN(C3CCC(=O)CC3)CC1)C2
InChIKey: GYMQVVOWHCVGFF-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 10 nM (pChEMBL 8)
Descriptors: MW 373.43, ALogP 1.86, HBA 4, HBD 1, PSA 83.71, QED 0.88
Compound (SMILES): CN(CC(=O)Nc1ccc2[nH]c(=O)c3ccccc3c2c1)C(=O)CCC[N+]1=c2cc3c(cc2CCC1)=Cc1ccc(N(C)C)cc1C3(C)C
InChIKey: YGMWYTAZFHVAQE-UHFFFAOYSA-O
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Mus musculus
UniProt: O88554
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 654.84, ALogP 4.53, HBA 4, HBD 2, PSA 88.52, QED 0.19
Compound (SMILES): CN(C)c1ccc2c(c1)C(C)(C)c1cc3c(cc1=C2)CCC[N+]=3CCCC(=O)NCCCCCCNCC(=O)Nc1ccc2[nH]c(=O)c3ccccc3c2c1
InChIKey: ZZPOTJWVHFJRIX-UHFFFAOYSA-O
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 739.99, ALogP 5.34, HBA 5, HBD 4, PSA 109.34, QED 0.07
Compound (SMILES): CN(/N=C(/c1ccccc1)c1cccc(C(=O)c2ccccc2)c1)C(N)=S
InChIKey: WZWOSKAWLSAHCD-GFMRDNFCSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 373.48, ALogP 3.85, HBA 3, HBD 1, PSA 58.69, QED 0.32
Compound (SMILES): NC(=S)N/N=C(/c1cc(Br)cc(C(=O)c2ccccc2F)c1)c1ccccc1F
InChIKey: CJQRVFLVSKNGST-XHPQRKPJSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 = 8.12 nM (pChEMBL 8.09000015258789)
Descriptors: MW 474.33, ALogP 4.54, HBA 3, HBD 2, PSA 67.48, QED 0.25
Compound (SMILES): NC(=S)N/N=C(/c1ccc(F)cc1)c1cccc(C(=O)c2ccc(F)cc2)c1
InChIKey: SWNLGOQSAKPQHP-PLRJNAJWSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 = 24.3 nM (pChEMBL 7.610000133514404)
Descriptors: MW 395.43, ALogP 3.78, HBA 3, HBD 2, PSA 67.48, QED 0.3
Compound (SMILES): COc1ccc(/C(=N/NC(N)=S)c2cccc(/C(=N/NC(N)=S)c3ccc(O)cc3)c2)cc1
InChIKey: SCMIRCLRIGLBMK-DSKJESRBSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 478.6, ALogP 2.57, HBA 6, HBD 5, PSA 130.28, QED 0.2
Compound (SMILES): COc1ccc(C(=O)c2cccc(/C(=N/NC(N)=S)c3ccc(O)cc3)c2)cc1
InChIKey: LRIJLAPJGORVAU-HIXSDJFHSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 405.48, ALogP 3.22, HBA 5, HBD 3, PSA 96.94, QED 0.25
Compound (SMILES): COc1ccc(/C(=N/NC(N)=S)c2cccc(C(=O)c3ccc(O)cc3)c2)cc1
InChIKey: VADUZVGRWOAHHK-GFMRDNFCSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 405.48, ALogP 3.22, HBA 5, HBD 3, PSA 96.94, QED 0.25
Compound (SMILES): COc1ccc(/C(=N/NC(N)=S)c2cccc(/C(=N/NC(N)=S)c3ccc(OC)cc3)c2)cc1
InChIKey: HRGOYWXRFSGTBN-KKTFQPMKSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 = 587 nM (pChEMBL 6.230000019073486)
Descriptors: MW 492.63, ALogP 2.88, HBA 6, HBD 4, PSA 119.28, QED 0.22
Compound (SMILES): CC(C)Oc1ccc(/C(=N/NC(N)=S)c2cccc(/C(=N/NC(N)=S)c3ccc(OC(C)C)cc3)c2)cc1
InChIKey: YKVBQHPKLZUYJI-IEPGDLOPSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 548.74, ALogP 4.43, HBA 6, HBD 4, PSA 119.28, QED 0.17
Compound (SMILES): NC(=S)N/N=C(/c1ccc(Br)cc1)c1cccc(/C(=N/NC(N)=S)c2ccc(Br)cc2)c1
InChIKey: KSHROFWRHTXIMD-RIRMOVKSSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Biological Assay: Human liver Cathepsin L (Sigma) was preincubated with test compounds at various concentrations for 5 minutes at 25C. The assay was initiated by addition of substrate Z-Phe-Arg-aminomethylcoumarin (Z-F-R-AMC Bacchem) and the final assay conditions were 1 nM cathepsin L, 50 uM Z-F-R-AMC, 100 mM sodium acetate pH 5.5, 1 mM EDTA (Omnipure), 3 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 2.0% DMSO (Acros). Test compounds were serially diluted with DMSO and water to include a final concentration range of 10 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 25C. using black 96-well Corning 3686 assay microplates with a Thermo Fluoroskan Ascent FL microplate reader at excitation and emission filter wavelengths of 355 nm and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 590.37, ALogP 4.38, HBA 4, HBD 4, PSA 100.82, QED 0.19
Compound (SMILES): CC[C@@H](NS(=O)(=O)CCCn1ccc(=O)[nH]c1=O)c1cccc(OCC2CC2)c1
InChIKey: ZBQHBTWRHZETFT-GOSISDBHSA-N
Target: Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P33316
Assay: Inhibition Assay: The inhibitory activity of these compounds of the present invention against human dUTPase was determined by measuring the production of [5-3H]deoxyuridine monophosphate (hereinafter, referred to as [5-3H]dUMP) from [5-3H]deoxyuridine triphosphate (hereinafter, referred to as [5-3H]dUTP) according to a method shown below.Specifically, 0.2 mL in total of a solution containing 0.02 mL of 1 uM dUTP (including 588 Bq/mL [5-3H]dUTP), 0.05 mL of a 0.2 M Tris buffer solution (pH 7.4), 0.05 mL of 16 mM magnesium chloride, 0.02 mL of 20 mM 2-mercaptoethanol, 0.02 mL of a 1% aqueous solution of fetal bovine serum-derived albumin, 0.02 mL of varying concentrations of test compound solutions or pure water as a control, and 0.02 mL of a solution of human dUTPase, which is expressed in E. coli and then purified, was incubated at 37 C. for 15 minutes. After the incubation, the solution was heated at 100 C. for 1 minute to terminate the reaction, followed by centrifugation at 15000 rpm for 2 minutes.
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 421.52, ALogP 1.79, HBA 6, HBD 2, PSA 110.26, QED 0.57