lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccccc2)on1
InChIKey: FRXRVVOCWBNHOQ-HOTGVXAUSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 474.47, ALogP 0.46, HBA 7, HBD 5, PSA 201.92, QED 0.26
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1noc(-c2ccccc2)n1
InChIKey: MNXXFUIRJNLTHG-KBPBESRZSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 475.46, ALogP -0.15, HBA 8, HBD 5, PSA 214.81, QED 0.24
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1csc(-c2ccccc2)n1
InChIKey: XNQPIVCSZRQAQO-HOTGVXAUSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 490.54, ALogP 0.93, HBA 7, HBD 5, PSA 188.78, QED 0.26
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1ccc(Oc2ccccc2)cc1
InChIKey: ACXIBBRPTTWRDM-PMACEKPBSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 499.52, ALogP 1.6, HBA 6, HBD 5, PSA 185.12, QED 0.24
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1ccc(COc2ccccc2)cc1
InChIKey: RAOGWYCOADLHPD-SFTDATJTSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 513.55, ALogP 1.38, HBA 6, HBD 5, PSA 185.12, QED 0.22
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1ccc(C#Cc2ccccc2)cc1
InChIKey: AVFCHUYQSZAIFE-VXKWHMMOSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 507.54, ALogP 1.2, HBA 5, HBD 5, PSA 175.89, QED 0.25
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1ccc(I)cc1
InChIKey: GSEYFLJSDKPLAI-KBPBESRZSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 533.32, ALogP 0.41, HBA 5, HBD 5, PSA 175.89, QED 0.23
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1ccc(-c2ncccn2)cc1
InChIKey: VIPIKALUTUDDKU-IRXDYDNUSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 485.5, ALogP 0.26, HBA 7, HBD 5, PSA 201.67, QED 0.25
Compound (SMILES): Cn1ccc(-c2ccc(CCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(N)=O)cc2)n1
InChIKey: YUQQWAKBRAEWQZ-ROUUACIJSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 487.51, ALogP 0.2, HBA 7, HBD 5, PSA 193.71, QED 0.25
Compound (SMILES): Cc1nc(-c2ccc(CCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(N)=O)cc2)no1
InChIKey: PLIPLRCYJWMTFY-HOTGVXAUSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 489.49, ALogP 0.16, HBA 8, HBD 5, PSA 214.81, QED 0.24
Compound (SMILES): CC[C@H](NC(=O)CCc1ccc(-c2csnn2)cc1)C(=O)N[C@@H](CCC(=O)O)C(N)=O
InChIKey: BFJIOGLKGISOKV-GJZGRUSLSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 442 nM (pChEMBL 6.360000133514404)
Descriptors: MW 447.52, ALogP 0.87, HBA 7, HBD 4, PSA 164.37, QED 0.37
Compound (SMILES): CC[C@H](NC(=O)CCc1ccc(-n2cccc2)cc1)C(=O)N[C@@H](CCC(=O)O)C(N)=O
InChIKey: UOTSSZSXOLHXGG-ROUUACIJSA-N
Target: Stromelysin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P09238
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 428.49, ALogP 1.14, HBA 5, HBD 4, PSA 143.52, QED 0.4
Compound (SMILES): C[N+]1(C)C2CCC1[C@H](OC(=O)[C@@](O)(c1ccccc1)C1CCCC1)C2
InChIKey: GIQCKBPBJOZAKR-SDVBZNEUSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Radioligand Binding Assay: Radioligand binding studies were carried out with M3 receptor cell homogenates as described (Peralta et al., The EMBO Journal 6, 3923-3929, (1987)). Incubations of test ligands (or standard) with 0.2 nM [3H]4-DAMP were incubated for 120 minutes at 22 C. using human M3 receptor-expressing cell homogenates. Specific ligand binding to the receptors was defined as the difference between the total radioligand binding and the nonspecific binding determined in the presence of an excess of unlabelled ligand (10 atropine). The results were expressed as a percent of control specific binding ((measured specific binding/control specific binding)x100) obtained in the presence of various concentrations of the test compounds.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 344.48, ALogP 2.99, HBA 3, HBD 1, PSA 46.53, QED 0.67
Compound (SMILES): C[N+]1(C)C2CCC1[C@@H](OC(=O)[C@@](O)(c1ccccc1)C1CCCC1)C2
InChIKey: GIQCKBPBJOZAKR-KWOGNLBTSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Radioligand Binding Assay: Radioligand binding studies were carried out with M3 receptor cell homogenates as described (Peralta et al., The EMBO Journal 6, 3923-3929, (1987)). Incubations of test ligands (or standard) with 0.2 nM [3H]4-DAMP were incubated for 120 minutes at 22 C. using human M3 receptor-expressing cell homogenates. Specific ligand binding to the receptors was defined as the difference between the total radioligand binding and the nonspecific binding determined in the presence of an excess of unlabelled ligand (10 atropine). The results were expressed as a percent of control specific binding ((measured specific binding/control specific binding)x100) obtained in the presence of various concentrations of the test compounds.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 344.48, ALogP 2.99, HBA 3, HBD 1, PSA 46.53, QED 0.67
Compound (SMILES): C[N+]1(C)C2CCC1[C@@H](OC(=O)[C@](O)(c1ccccc1)C1CCCC1)C2
InChIKey: GIQCKBPBJOZAKR-XSNSTOHYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Radioligand Binding Assay: Radioligand binding studies were carried out with M3 receptor cell homogenates as described (Peralta et al., The EMBO Journal 6, 3923-3929, (1987)). Incubations of test ligands (or standard) with 0.2 nM [3H]4-DAMP were incubated for 120 minutes at 22 C. using human M3 receptor-expressing cell homogenates. Specific ligand binding to the receptors was defined as the difference between the total radioligand binding and the nonspecific binding determined in the presence of an excess of unlabelled ligand (10 atropine). The results were expressed as a percent of control specific binding ((measured specific binding/control specific binding)x100) obtained in the presence of various concentrations of the test compounds.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 344.48, ALogP 2.99, HBA 3, HBD 1, PSA 46.53, QED 0.67
Compound (SMILES): Cc1cnc2[nH]cc(Cc3cnc(NCc4ccc(Cl)nc4)nc3)c2c1
InChIKey: YJRASZMPGGZLLW-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.84, ALogP 3.91, HBA 5, HBD 2, PSA 79.38, QED 0.52
Compound (SMILES): Cc1cnc2[nH]cc(Cc3cnc(NCc4cccc(C)n4)nc3)c2c1
InChIKey: QEZRYOVBHVLYKM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.42, ALogP 3.57, HBA 5, HBD 2, PSA 79.38, QED 0.58
Compound (SMILES): Cc1cnc2[nH]cc(Cc3cnc(NCc4cccc(N5CCOCC5)n4)nc3)c2c1
InChIKey: ZBJOFNRBXVLOMA-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 415.5, ALogP 3.1, HBA 7, HBD 2, PSA 91.85, QED 0.5
Compound (SMILES): Cc1cnc2[nH]cc(Cc3cnc(NCc4cccc(N5CCCC5)n4)nc3)c2c1
InChIKey: BLPWIRCAXJRMJZ-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Biochemical Assay: In one assay the biochemical activity IC50 values are determined with respect to inhibition of c-Kit kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested are dissolved in DMSO to a concentration of 20 mM. These are diluted 30 uL into 120 uL of DMSO (4 mM) and 1 uL is added to an assay plate. These are then serially diluted 1:2 (50 uL to 100 uL DMSO) for a total of 8 points. Plates are prepared such that each kinase reaction is 20 uL in 1x kinase buffer (25 mM HEPES, pH 7.5, 2 mM MgCl2, 2 mM MnCl2, 0.01% Tween-20, 1 mM DTT, 0.01% BSA), 5% DMSO and 100 uM ATP. Substrate is 30 nM biotin-(E4Y)10 (Millipore). C-kit kinase (obtained from Millipore (#14-559) or is prepared as described in U.S. Patent Application Publication Number 2009/0076046, the disclosure of which is hereby incorporated by reference as it relates to this assay) is at 0.75 ng per sample.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 399.5, ALogP 3.86, HBA 6, HBD 2, PSA 82.62, QED 0.51
Compound (SMILES): COc1ncccc1CNc1ncc(Cc2c[nH]c3ncc(C)cc23)cn1
InChIKey: BPZSDIOZLNSESC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 360.42, ALogP 3.27, HBA 6, HBD 2, PSA 88.61, QED 0.55
Compound (SMILES): Cc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(C(F)(F)F)cn3)[C@@H]2C)c(-n2nccn2)n1
InChIKey: JTVBTTLMGGYEPR-XJKSGUPXSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession numberNM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022) , 10%FBS, IX Pen/Strep, IX NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4Â°C), the supernatant was aspirated and the pellets frozen and stored at -80Â°C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity = 29.6 Ci/mmol).
Measurement: Ki = 7501 nM (pChEMBL 5.119999885559082)
Descriptors: MW 446.44, ALogP 2.88, HBA 8, HBD 1, PSA 101.72, QED 0.66
Compound (SMILES): CCOc1ccc(/C=C2\SC(=S)N(CCN)C2=O)cc1
InChIKey: GYJTUKQKGFMUTI-XFXZXTDPSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Fluorescence Quenching Assay: CADD and biological testing to identify compounds that interact with novel ERK substrate docking sites. The known ERK2 docking sites include the DRS (site 1) and FRS (site 5) regions, whereas predicted docking sites are labeled sites 2-4 (Table 6). One compound, 76, that targets the DRS is being marketed by Calbiochem/EMD Biosciences (Cat#328006) as an ERK inhibitor. Successful inhibitor identification to date has been based on a combination of fluorescence quenching (FQ) of ERK2 wild type and docking site mutants in the presence of test compound.
Measurement: Kd = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 308.43, ALogP 2.25, HBA 5, HBD 1, PSA 55.56, QED 0.67
Compound (SMILES): NCCN1C(=O)/C(=C/c2ccc3c(c2)OCO3)SC1=S
InChIKey: BUBDMZSKWQUTPR-WDZFZDKYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Fluorescence Quenching Assay: CADD and biological testing to identify compounds that interact with novel ERK substrate docking sites. The known ERK2 docking sites include the DRS (site 1) and FRS (site 5) regions, whereas predicted docking sites are labeled sites 2-4 (Table 6). One compound, 76, that targets the DRS is being marketed by Calbiochem/EMD Biosciences (Cat#328006) as an ERK inhibitor. Successful inhibitor identification to date has been based on a combination of fluorescence quenching (FQ) of ERK2 wild type and docking site mutants in the presence of test compound.
Measurement: Kd > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 308.38, ALogP 1.58, HBA 6, HBD 1, PSA 64.79, QED 0.68
Compound (SMILES): O=S1(=O)C=CC(OS(=O)(=O)c2ccccc2)C1
InChIKey: RFHUNIXPGHBTTE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Fluorescence Quenching Assay: CADD and biological testing to identify compounds that interact with novel ERK substrate docking sites. The known ERK2 docking sites include the DRS (site 1) and FRS (site 5) regions, whereas predicted docking sites are labeled sites 2-4 (Table 6). One compound, 76, that targets the DRS is being marketed by Calbiochem/EMD Biosciences (Cat#328006) as an ERK inhibitor. Successful inhibitor identification to date has been based on a combination of fluorescence quenching (FQ) of ERK2 wild type and docking site mutants in the presence of test compound.
Measurement: Kd = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 274.32, ALogP 0.7, HBA 5, HBD 0, PSA 77.51, QED 0.76
Compound (SMILES): CCOc1ccc(/C=C2\SC(=S)N(CCNCc3ccc(C(=O)O)cc3)C2=O)cc1
InChIKey: GWTVSEKWJKUHKU-UYRXBGFRSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: Fluorescence Quenching Assay: CADD and biological testing to identify compounds that interact with novel ERK substrate docking sites. The known ERK2 docking sites include the DRS (site 1) and FRS (site 5) regions, whereas predicted docking sites are labeled sites 2-4 (Table 6). One compound, 76, that targets the DRS is being marketed by Calbiochem/EMD Biosciences (Cat#328006) as an ERK inhibitor. Successful inhibitor identification to date has been based on a combination of fluorescence quenching (FQ) of ERK2 wild type and docking site mutants in the presence of test compound.
Measurement: Kd = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 442.56, ALogP 3.77, HBA 6, HBD 2, PSA 78.87, QED 0.35
Compound (SMILES): CCOc1ccc(/C=C2\SC(=S)N(CCNc3nc(Cl)nc(Cl)n3)C2=O)cc1
InChIKey: LUHOQEHJCOMYJI-XFXZXTDPSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: Fluorescence Quenching Assay: CADD and biological testing to identify compounds that interact with novel ERK substrate docking sites. The known ERK2 docking sites include the DRS (site 1) and FRS (site 5) regions, whereas predicted docking sites are labeled sites 2-4 (Table 6). One compound, 76, that targets the DRS is being marketed by Calbiochem/EMD Biosciences (Cat#328006) as an ERK inhibitor. Successful inhibitor identification to date has been based on a combination of fluorescence quenching (FQ) of ERK2 wild type and docking site mutants in the presence of test compound.
Measurement: Kd = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 456.38, ALogP 3.89, HBA 8, HBD 1, PSA 80.24, QED 0.5
Compound (SMILES): Cn1cc(-c2cccc(N3CCc4c(sc5c4CC(C)(C)C5)C3=O)c2CO)cc(Nc2ccncn2)c1=O
InChIKey: QAESSIFTPVEYRY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human B-cells assessed as decrease in BCR-stimulated B-cell proliferation after 8 hrs by [3H]-thymidine incorporation assay
Measurement: EC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 527.65, ALogP 4.47, HBA 8, HBD 2, PSA 100.35, QED 0.4
Compound (SMILES): CN1CCN(c2ccc(Nc3cc(-c4cc(F)cc(N5CCn6c(cc7c6CCCC7)C5=O)c4CO)cn(C)c3=O)nc2)CC1
InChIKey: MQQGYKZCGFDOOC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood-derived CD19+ B cells assessed as suppression of anti-IgM stimulated-CD69 expression preincubated for 1 hr followed by IgM stimulation for 18 hrs by FACS analysis
Measurement: IC50 = 27.6 nM (pChEMBL 7.559999942779541)
Descriptors: MW 611.72, ALogP 3.91, HBA 9, HBD 2, PSA 98.87, QED 0.34
Compound (SMILES): Cn1cc(-c2cc(F)cc(N3CCn4c(cc5c4CCCC5)C3=O)c2CO)cc(Nc2ccc(N3CCN(C4COC4)CC3)cn2)c1=O
InChIKey: CMLXXBAEHGHZRO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood-derived CD19+ B cells assessed as suppression of anti-IgM stimulated-CD69 expression preincubated for 1 hr followed by IgM stimulation for 18 hrs by FACS analysis
Measurement: IC50 = 36.5 nM (pChEMBL 7.440000057220459)
Descriptors: MW 653.76, ALogP 3.68, HBA 10, HBD 2, PSA 108.1, QED 0.31
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)C=CSC(N)=N1
InChIKey: ILCHBMXUEANZSX-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE-1 (unknown origin)
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 360.39, ALogP 3.4, HBA 5, HBD 2, PSA 80.37, QED 0.88
Compound (SMILES): Cc1cc(C(N)=S)cnc1C(=O)Nc1cc(C2(CF)COCC(N)=N2)ccn1
InChIKey: OTLWVMHTRDSPSA-UHFFFAOYSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of Human BACE-2: Recombinant BACE-2 (extracellular domain, expressed in baculovirus and purified using standard methods) at 0.1 to 10 nM concentrations is incubated with the test compound at various concentrations for 1 hour at room temperature in 10 to 100 mM acetate buffer, pH 4.5, containing 0.1% CHAPS. Synthetic fluorescence-quenched peptide substrate, derived from the sequence of APP and containing a suitable fluorophore-quencher pair, is added to a final concentration of 1 to 5 μM, and the increase in fluorescence is recorded at a suitable excitation/emission wavelength in a microplate spectro-fluorimeter for 5 to 30 minutes in 1-minute intervals. IC50 values are calculated from percentage of inhibition of BACE-2 activity as a function of the test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.46, ALogP 1.22, HBA 7, HBD 3, PSA 128.51, QED 0.64
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ncc(C#N)cc3Cl)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: LHTZVIDMVHFLLF-ZWKOTPCHSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of wild type APP751 (unknown origin) expressed in CHO cells
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 470.81, ALogP 3.32, HBA 7, HBD 2, PSA 126.28, QED 0.66
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ncc(C#N)cc3N)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: MWIIPGZITGHTPU-ZWKOTPCHSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of wild type APP751 (unknown origin) expressed in CHO cells
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 451.38, ALogP 2.25, HBA 8, HBD 3, PSA 152.3, QED 0.61
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ncc(OC(F)F)cc3Cl)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: DOJQNRYLSRMQDA-ZWKOTPCHSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of wild type APP751 (unknown origin) expressed in CHO cells
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 511.81, ALogP 4.05, HBA 7, HBD 2, PSA 111.72, QED 0.59
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ncc(C(F)(F)F)cc3Cl)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: PSBBWFNMHDUTRH-DLBZAZTESA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Irreversible inhibition of CYP2D6 in human liver microsomes incubated for 10 mins in presence of NADPH by mass spectrometry
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 513.8, ALogP 4.46, HBA 6, HBD 2, PSA 102.49, QED 0.59
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ncc(C(F)(F)F)nc3N)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: HUQALVJHHCENTE-JKSUJKDBSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human Cathepsin D using Mca-GKPILFFRLK(DNP)D-R-NH2 as a substrate
Measurement: IC50 = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 495.36, ALogP 2.79, HBA 8, HBD 3, PSA 141.4, QED 0.56
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3nc4ccn(CC(F)F)c4nc3N)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: WBCXJAZBPSKARJ-VQTJNVASSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of Human BACE-2: Recombinant BACE-2 (extracellular domain, expressed in baculovirus and purified using standard methods) at 0.1 to 10 nM concentrations is incubated with the test compound at various concentrations for 1 hour at room temperature in 10 to 100 mM acetate buffer, pH 4.5, containing 0.1% CHAPS. Synthetic fluorescence-quenched peptide substrate, derived from the sequence of APP and containing a suitable fluorophore-quencher pair, is added to a final concentration of 1 to 5 μM, and the increase in fluorescence is recorded at a suitable excitation/emission wavelength in a microplate spectro-fluorimeter for 5 to 30 minutes in 1-minute intervals. IC50 values are calculated from percentage of inhibition of BACE-2 activity as a function of the test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.43, ALogP 2.99, HBA 9, HBD 3, PSA 146.33, QED 0.43
Compound (SMILES): CNCC(Nc1ncnc2c(C(N)=O)cccc12)c1ccccc1
InChIKey: KFUGVCOVSKGHMS-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Enzyme Assay: The Aurora assays described here are performed on two Caliper Life Sciences systems: the LC3000 and the Desktop Profiler. These provide data on enzyme activity via measurement of the relative amounts of phosphorylated or unphosphorylated fluorescently labelled substrate peptide at the end of an enzymatic reaction. These different states of peptide are resolved by applying a potential difference across the sample. The presence of the charged phosphate group on the product (as opposed to the substrate) causes a different peptide mobility between the two peptides. This is visualized by excitation of the fluorescent label on the substrate and product peptides and represented as peaks within the analysis software.
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 321.38, ALogP 2.1, HBA 5, HBD 3, PSA 92.93, QED 0.65
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2[nH]c(-c3ccc(O)cc3)cc2-c2ccoc2)cc1
InChIKey: OUFJXJJAONPLLU-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 753.7 nM (pChEMBL 6.119999885559082)
Descriptors: MW 417.42, ALogP 3.7, HBA 5, HBD 5, PSA 127.59, QED 0.24
Compound (SMILES): COc1ccc(-c2cc(-c3ccccc3)[nH]c2C(=O)Nc2cccc(CC(=O)NO)c2)cc1
InChIKey: IRPKGHDXTSHWAC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 441.49, ALogP 4.66, HBA 4, HBD 4, PSA 103.45, QED 0.25
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2[nH]c(-c3ccc(O)cc3)cc2-c2ccsc2)cc1
InChIKey: GPGGCNQZIWRUGW-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 277 nM (pChEMBL 6.559999942779541)
Descriptors: MW 433.49, ALogP 4.16, HBA 5, HBD 5, PSA 114.45, QED 0.23
Compound (SMILES): COc1ccc(-c2cc(-c3ccccc3)[nH]c2C(=O)NCc2ccc(C(=O)Nc3ccccc3N)cc2)cc1
InChIKey: HXVFEQPXJNUVNL-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 451.3 nM (pChEMBL 6.349999904632568)
Descriptors: MW 516.6, ALogP 6.12, HBA 4, HBD 4, PSA 109.24, QED 0.19
Compound (SMILES): COc1ccc(-c2cc(-c3ccccc3)[nH]c2C(=O)NCc2ccc(C(=O)Nc3ccccc3S)cc2)cc1
InChIKey: DPKPNPAZPYFQLM-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 1909 nM (pChEMBL 5.71999979019165)
Descriptors: MW 533.65, ALogP 6.83, HBA 4, HBD 4, PSA 83.22, QED 0.17
Compound (SMILES): COc1ccc(-c2cc(-c3ccccc3)[nH]c2C(=O)NCc2ccc(C(=O)Nc3ccccn3)cc2)cc1
InChIKey: CJPQHCIMSKHOBF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 502.57, ALogP 5.93, HBA 4, HBD 3, PSA 96.11, QED 0.24
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC(=O)c2[nH]c(-c3ccoc3)cc2-c2ccc(O)cc2)cc1
InChIKey: MMSGALSNHXCNDK-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 492.54, ALogP 5.41, HBA 5, HBD 5, PSA 133.38, QED 0.19
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC(=O)c2[nH]c(-c3ccc(O)cc3)cc2-c2ccccc2)cc1
InChIKey: NRCPKXNQDZLOCF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 433 nM (pChEMBL 6.360000133514404)
Descriptors: MW 502.57, ALogP 5.82, HBA 4, HBD 5, PSA 120.24, QED 0.18
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC(=O)c2[nH]c(-c3ccsc3)cc2-c2ccc(O)cc2)cc1
InChIKey: SEYQQVKFMOLZCN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 = 222 nM (pChEMBL 6.650000095367432)
Descriptors: MW 508.6, ALogP 5.88, HBA 5, HBD 5, PSA 120.24, QED 0.18
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC(=O)c2[nH]c(-c3ccc(O)cc3)cc2-c2ccoc2)cc1
InChIKey: RZUFVMUYNQBONC-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Enzyme Assay: The reactions were carried out in a 96-well microplate for fluorometry in a 50 μl reaction volume. After the deacetylation reaction, Fluor-de-Lys-Developer (BioMol Cat. # KI-105) was added to each well to digest the deacetylated substrate, thus producing the fluorescent signal. The reaction was allowed to develop for 45 minutes at 30° C. with 5% CO2; then the fluorescent signal was measured with an excitation wavelength at 360 nm and an emission wavelength at 460 nm in a microplate-reading fluorometer (GeminiXS; Molecular Devices, Sunnyvale, Calif.). A curve of Deacetylated Standard (Biomol, Cat. # KI-142; made from 100 μM with 1:2 dilution and 10-doses, 6 μl) allowed the conversion of fluorescent signal into micromoles of deacetylated product.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 492.54, ALogP 5.41, HBA 5, HBD 5, PSA 133.38, QED 0.19
Compound (SMILES): C[C@H](NC(=O)c1c(C(F)F)nn(C)c1Oc1cccc(C(F)(F)F)c1)c1ccc(C(=O)O)cc1
InChIKey: MKLKAQMPKHNQPR-NSHDSACASA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Antagonist activity at human EP2 expressed in CHO cells coexpressing G16-alpha assessed as intracellular calcium flux preincubated for 15 mins followed by addition of PGE2 by calcium flux assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.39, ALogP 5.36, HBA 5, HBD 2, PSA 93.45, QED 0.44
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: FBDOWURNGYMLPJ-IBGZPJMESA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 455.9, ALogP 3.43, HBA 5, HBD 3, PSA 135.52, QED 0.43
Compound (SMILES): NC(=O)[C@@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: KOVQMCGGWATESY-YADHBBJMSA-N
Target: Stromelysin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P09238
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 585.01, ALogP 2.78, HBA 7, HBD 5, PSA 201.92, QED 0.18
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: KOVQMCGGWATESY-FCHUYYIVSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 585.01, ALogP 2.78, HBA 7, HBD 5, PSA 201.92, QED 0.18
Compound (SMILES): NC(=O)[C@@H](CCC(=O)O)NC(=O)[C@@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: KOVQMCGGWATESY-FGZHOGPDSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 585.01, ALogP 2.78, HBA 7, HBD 5, PSA 201.92, QED 0.18
Compound (SMILES): NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: QCVLVTVGVJUODZ-UNMCSNQZSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 243 nM (pChEMBL 6.610000133514404)
Descriptors: MW 570.99, ALogP 2.39, HBA 7, HBD 5, PSA 201.92, QED 0.19
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: MFTZEUCXFCXINH-UNMCSNQZSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 570.99, ALogP 2.39, HBA 7, HBD 5, PSA 201.92, QED 0.19
Compound (SMILES): NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: PZMQNEDVJSDLAW-SFTDATJTSA-N
Target: Stromelysin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P09238
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 556.96, ALogP 2, HBA 7, HBD 5, PSA 201.92, QED 0.21
Compound (SMILES): CC[C@H](NC(=O)[C@H](CCCOC=O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1)C(N)=O
InChIKey: CNPRJTXDIHRZPF-ZEQRLZLVSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 254 nM (pChEMBL 6.590000152587891)
Descriptors: MW 555.03, ALogP 3.41, HBA 7, HBD 3, PSA 153.62, QED 0.19
Compound (SMILES): NC(=O)[C@H](CCCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: LFUNCOOVDREPBK-GOTSBHOMSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 599.04, ALogP 3.17, HBA 7, HBD 5, PSA 201.92, QED 0.16
Compound (SMILES): NC(=O)[C@H](CCCC(=O)O)NC(=O)[C@H](CCCOC=O)NC(=O)CCc1cc(-c2ccc(-c3cccc(Cl)c3)cc2)no1
InChIKey: QDHXNZRPVLUOML-DQEYMECFSA-N
Target: Stromelysin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P09238
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 613.07, ALogP 3.26, HBA 8, HBD 4, PSA 190.92, QED 0.12
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)CCc1cc(-c2ccccc2)no1
InChIKey: HCTHWCGSCVVHLJ-ZDUSSCGKSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 398 nM (pChEMBL 6.400000095367432)
Descriptors: MW 345.36, ALogP 1.11, HBA 5, HBD 3, PSA 135.52, QED 0.62
Compound (SMILES): CC[C@H](NC(=O)CCc1cc(-c2ccc(-c3ccccc3)cc2)no1)C(=O)N[C@@H](CCC(=O)O)C(N)=O
InChIKey: FFHINXVCVWQCSG-VXKWHMMOSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 506.56, ALogP 2.67, HBA 6, HBD 4, PSA 164.62, QED 0.28
Compound (SMILES): NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3ccccc3)cc2)no1
InChIKey: HXOLPPZDNXMRHR-UNMCSNQZSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 536.54, ALogP 1.74, HBA 7, HBD 5, PSA 201.92, QED 0.2
Compound (SMILES): CC[C@H](NC(=O)CCc1cc(-c2ccc(-c3ccccc3)cc2)no1)C(=O)N[C@@H](CC(=O)O)C(N)=O
InChIKey: BMJUABISSDGKOA-UNMCSNQZSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 492.53, ALogP 2.28, HBA 6, HBD 4, PSA 164.62, QED 0.3
Compound (SMILES): NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CCc1cc(-c2ccc(-c3ccccc3)cc2)no1
InChIKey: NZUPMMOEPOVBQE-SFTDATJTSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition Assay: The inhibition tests and the evaluation of the inhibition constants (Ki) on the various MMPs were carried out as described by Devel et al. (Devel et al. 2006 J. Biol. Chem. (7)).
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 522.51, ALogP 1.35, HBA 7, HBD 5, PSA 201.92, QED 0.22