lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NC(Cc1c[nH]cn1)C(=O)O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: UABZPISCAICSOU-KTJHOKPASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 368 nM (pChEMBL 6.429999828338623)
Descriptors: MW 546.67, ALogP 3.83, HBA 7, HBD 3, PSA 133.21, QED 0.41
Compound (SMILES): O=C(NC(Cc1ccccc1)C(=O)O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: DJBBTDZPDUSNJJ-MIGYSTJESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 307.1 nM (pChEMBL 6.510000228881836)
Descriptors: MW 556.71, ALogP 5.1, HBA 6, HBD 2, PSA 104.53, QED 0.42
Compound (SMILES): Cc1c(C(=O)O)sc2ncnc(Nc3ccc(F)cc3OC(CF)CF)c12
InChIKey: FRGARKJLNFHDAI-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition Assay: Inhibition of kinase activity of Mnk1 and Mnk2a was assessed with the same assay system, using pre-activated GST-Mnk1 or GST-Mnk2a, respectively. The kinase reaction contains 30 uM substrate peptide, 20 uM ATP, 60 nM ligand and one of either 25 nM pre-activated Mnk1 or 2.5 nM pre-activated Mnk2a. The reaction buffer conditions are 16 mM HEPES/KOH pH 7.4, 8 mM MgCl2, 0.4 mM DTT, 0.08% (w/v) bovine serum albumin (BSA, Sigma, Germany, cat. no. A3059), 0.008% (w/v) Pluronic F127 (Sigma, Germany, cat. no. P2443), 3% (v/v) DMSO (Applichem, Germany, cat. no. A3006). The kinase reaction is at 30 C. for 40 min. The kinase reaction is terminated by addition of 0.67 reaction volumes of 1 uM antibody in 20 mM HEPES/KOH pH 7.4, 50 mM ethylenediaminetetraacetic acid, disodium salt (EDTA, Sigma, Germany, cat. no. E5134), 0.5 mM DTT, 0.05% (w/v) polyoxyethylene-sorbitan monolaureate (Tween 20, Sigma, Germany, cat. no. P7949).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 397.38, ALogP 4.27, HBA 6, HBD 2, PSA 84.34, QED 0.62
Compound (SMILES): CC(C)N1CC2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: HYTFHLKGMUVBOD-SBXXRYSUSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): Clc1ccc(C23CC2CN(C2CC2)C3)cc1Cl
InChIKey: DLNQEYMDSOUAEK-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 268.19, ALogP 3.73, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CC(C)(C)N1CC2CC2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: HUWILRCAXKHYEE-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 284.23, ALogP 4.37, HBA 1, HBD 0, PSA 3.24, QED 0.74
Compound (SMILES): CN1CC2CC2(c2ccc(F)c(F)c2)C1
InChIKey: WXIVKHRXEAQSCE-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 209.24, ALogP 2.17, HBA 1, HBD 0, PSA 3.24, QED 0.68
Compound (SMILES): Fc1ccc(C23CNCC2C3)cc1Cl
InChIKey: DJQGRQUSJZIZJM-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 211.67, ALogP 2.34, HBA 1, HBD 1, PSA 12.03, QED 0.75
Compound (SMILES): CN1CC2CC2(c2ccc(F)c(Cl)c2)C1
InChIKey: MIRHDPAAZCWTAT-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 225.69, ALogP 2.68, HBA 1, HBD 0, PSA 3.24, QED 0.71
Compound (SMILES): CN1CC2CC2(c2ccc(Cl)cc2Cl)C1
InChIKey: NINMSEOZKXYKQY-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 242.15, ALogP 3.2, HBA 1, HBD 0, PSA 3.24, QED 0.73
Compound (SMILES): Cc1cc(C23CC2CN(C)C3)ccc1F
InChIKey: ZJDFOPYAGRPFLM-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 205.28, ALogP 2.34, HBA 1, HBD 0, PSA 3.24, QED 0.68
Compound (SMILES): Cc1ccc(C23CC2CN(C)C3)cc1F
InChIKey: RKQIRCIDIAEOQG-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 205.28, ALogP 2.34, HBA 1, HBD 0, PSA 3.24, QED 0.68
Compound (SMILES): CN1CC2CC2(c2ccc3ccccc3c2)C1
InChIKey: COLJOGVSPPXZNW-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 223.32, ALogP 3.04, HBA 1, HBD 0, PSA 3.24, QED 0.72
Compound (SMILES): CO[C@H]1CC[C@@H](N2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)CC1
InChIKey: MLNXSIDFWZVCJU-WOVMCDHWSA-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 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 371.48, ALogP 2.16, HBA 4, HBD 1, PSA 75.87, QED 0.88
Compound (SMILES): CO[C@H]1CC[C@H](N2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)CC1
InChIKey: MLNXSIDFWZVCJU-JCNLHEQBSA-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 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 371.48, ALogP 2.16, HBA 4, HBD 1, PSA 75.87, QED 0.88
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN([C@H]3CC[C@@H](CO)CC3)CC1)C2
InChIKey: AZXKIFDWCMPCMU-FZNQNYSPSA-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 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 371.48, ALogP 1.76, HBA 4, HBD 2, PSA 86.87, QED 0.84
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN([C@H]3CC[C@H](CO)CC3)CC1)C2
InChIKey: AZXKIFDWCMPCMU-KOMQPUFPSA-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 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 371.48, ALogP 1.76, HBA 4, HBD 2, PSA 86.87, QED 0.84
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: 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 = 4600 nM (pChEMBL 5.340000152587891)
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: 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 = 2300 nM (pChEMBL 5.639999866485596)
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: 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 = 3950 nM (pChEMBL 5.400000095367432)
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(Cc3ccc(F)cc3F)CC1)C2
InChIKey: KCTRCOAVSQQBQD-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 = 5770 nM (pChEMBL 5.239999771118164)
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: 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 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: 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 = 200 nM (pChEMBL 6.699999809265137)
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: 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 = 320 nM (pChEMBL 6.5)
Descriptors: MW 446.6, ALogP 3.12, HBA 4, HBD 1, PSA 69.88, QED 0.74
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: 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 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 430.55, ALogP 3.94, HBA 4, HBD 1, PSA 71.57, QED 0.67
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: 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 = 900 nM (pChEMBL 6.050000190734863)
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: 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 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: 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 = 230 nM (pChEMBL 6.639999866485596)
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: 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 = 260 nM (pChEMBL 6.579999923706055)
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: 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 = 260 nM (pChEMBL 6.579999923706055)
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: 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 = 330 nM (pChEMBL 6.480000019073486)
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: 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 = 110 nM (pChEMBL 6.960000038146973)
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: 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 = 5310 nM (pChEMBL 5.28000020980835)
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: 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 = 2660 nM (pChEMBL 5.579999923706055)
Descriptors: MW 377.49, ALogP 2.97, HBA 3, HBD 1, PSA 66.64, QED 0.87
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: 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): 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: 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 = 160 nM (pChEMBL 6.800000190734863)
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: 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 = 80 nM (pChEMBL 7.099999904632568)
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 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 = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 654.84, ALogP 4.53, HBA 4, HBD 2, PSA 88.52, QED 0.19
Compound (SMILES): CN(/N=C(/c1ccccc1)c1cccc(C(=O)c2ccccc2)c1)C(N)=S
InChIKey: WZWOSKAWLSAHCD-GFMRDNFCSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Biological Assay: Recombinant human procathepsin K was obtained from Enzo Life Sciences. Activation of the proenzyme was performed in 32.5 mM sodium acetate pH 3.5, EDTA 1 mM, NaCl 500 mM, human procathepsin K 5.5 uM, at room temperature. Activation times were optimized and varied between 35 and 150 minutes. Cathepsin K 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 1.5 nM cathepsin K, 50 uM Z-F-R-AMC, 150 mM sodium acetate pH 5.5, 2.5 mM EDTA (Omnipure), 2.5 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 4.0% 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.
Measurement: IC50 = 17.4 nM (pChEMBL 7.760000228881836)
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: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Biological Assay: Human liver Cathepsin B (Calbiochem) was pre-incubated with test compound at various concentrations for 5 minutes at 37C. The assay was initiated by addition of substrate Z-Arg-Arg-aminomethylcoumarin (Z-R-R-AMC Bacchem) and the final assay conditions were 1.1 nM cathepsin B, 60 uM Z-R-R-AMC, 126 mM sodium potassium phosphate pH 6.0 (Fisher), 0.3 mM EDTA (Omnipure), 2.7 mM DTT (Omnipure), 0.004% BRIJ 35 (Sigma), and 2.0% DMSO (Acros) in a final volume of 200 uL. Test compounds were serially diluted with DMSO and 0.01% BRIJ 35 to include a final concentration range of 20 uM to 10 pM. The reaction was monitored fluorometrically for 5 minutes at 37C. 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 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: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Biological Assay: Recombinant human procathepsin K was obtained from Enzo Life Sciences. Activation of the proenzyme was performed in 32.5 mM sodium acetate pH 3.5, EDTA 1 mM, NaCl 500 mM, human procathepsin K 5.5 uM, at room temperature. Activation times were optimized and varied between 35 and 150 minutes. Cathepsin K 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 1.5 nM cathepsin K, 50 uM Z-F-R-AMC, 150 mM sodium acetate pH 5.5, 2.5 mM EDTA (Omnipure), 2.5 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 4.0% 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.
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
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(OC)cc3)c2)cc1
InChIKey: HRGOYWXRFSGTBN-KKTFQPMKSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Biological Assay: Recombinant human procathepsin K was obtained from Enzo Life Sciences. Activation of the proenzyme was performed in 32.5 mM sodium acetate pH 3.5, EDTA 1 mM, NaCl 500 mM, human procathepsin K 5.5 uM, at room temperature. Activation times were optimized and varied between 35 and 150 minutes. Cathepsin K 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 1.5 nM cathepsin K, 50 uM Z-F-R-AMC, 150 mM sodium acetate pH 5.5, 2.5 mM EDTA (Omnipure), 2.5 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 4.0% 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.
Measurement: IC50 = 2105 nM (pChEMBL 5.679999828338623)
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: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Biological Assay: Recombinant human procathepsin K was obtained from Enzo Life Sciences. Activation of the proenzyme was performed in 32.5 mM sodium acetate pH 3.5, EDTA 1 mM, NaCl 500 mM, human procathepsin K 5.5 uM, at room temperature. Activation times were optimized and varied between 35 and 150 minutes. Cathepsin K 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 1.5 nM cathepsin K, 50 uM Z-F-R-AMC, 150 mM sodium acetate pH 5.5, 2.5 mM EDTA (Omnipure), 2.5 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 4.0% 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.
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: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Biological Assay: Recombinant human procathepsin K was obtained from Enzo Life Sciences. Activation of the proenzyme was performed in 32.5 mM sodium acetate pH 3.5, EDTA 1 mM, NaCl 500 mM, human procathepsin K 5.5 uM, at room temperature. Activation times were optimized and varied between 35 and 150 minutes. Cathepsin K 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 1.5 nM cathepsin K, 50 uM Z-F-R-AMC, 150 mM sodium acetate pH 5.5, 2.5 mM EDTA (Omnipure), 2.5 mM DTT (EMD), 0.01% BRIJ 35 (Sigma), and 4.0% 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.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 590.37, ALogP 4.38, HBA 4, HBD 4, PSA 100.82, QED 0.19