lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc2nc(-c3ccc4c(N)nc(N)nc4c3)n(CCCO)c2cc1C
InChIKey: KDNYRYCRFHVZNX-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 362.44, ALogP 2.81, HBA 7, HBD 3, PSA 115.87, QED 0.51
Compound (SMILES): COc1ccc2nc(SCCC(C)(F)F)n(-c3ccc4c(N)nc(N)nc4c3)c2c1
InChIKey: IYGGBRFBQQVMSV-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 430.48, ALogP 4.28, HBA 8, HBD 2, PSA 104.87, QED 0.44
Compound (SMILES): COc1cc2c(cc1CO)nc(-c1nccs1)n2-c1cc2nc(N)nc(N)c2cc1Cl
InChIKey: ATVFRKJIVAFJQN-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 320 nM (pChEMBL 6.5)
Descriptors: MW 453.92, ALogP 3.41, HBA 10, HBD 3, PSA 137.99, QED 0.38
Compound (SMILES): COc1cc2c(cc1CO)nc(-c1nccs1)n2-c1cc2nc(N)nc(N)c2cc1C
InChIKey: KDHIRSJXSHFBMF-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 433.5, ALogP 3.07, HBA 10, HBD 3, PSA 137.99, QED 0.39
Compound (SMILES): Cc1cc2c(N)nc(N)nc2cc1-c1cnc2[nH]ccc2c1
InChIKey: JTOMSJOIFXSANF-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 290.33, ALogP 2.65, HBA 5, HBD 3, PSA 106.5, QED 0.5
Compound (SMILES): Cc1cc2c(N)nc(N)nc2cc1-c1cc(CO)ncc1Cl
InChIKey: HYKSNPURZZNCNE-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 56 nM (pChEMBL 7.25)
Descriptors: MW 315.76, ALogP 2.31, HBA 6, HBD 3, PSA 110.94, QED 0.67
Compound (SMILES): COc1nc(CO)ncc1-c1cc2nc(N)nc(N)c2cc1C
InChIKey: NFUZPVBLDCGSHI-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 54.7 nM (pChEMBL 7.260000228881836)
Descriptors: MW 312.33, ALogP 1.06, HBA 8, HBD 3, PSA 133.06, QED 0.65
Compound (SMILES): COC(=O)c1ccc2c(c1)nc(-c1nccs1)n2-c1ccc2c(N)nc(N)nc2c1
InChIKey: MLRYLGRISSFLSZ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 417.45, ALogP 3.04, HBA 10, HBD 2, PSA 134.83, QED 0.43
Compound (SMILES): COc1cc(-c2cc3nc(N)nc(N)c3cc2C)cc(OC)c1OC
InChIKey: XNKZSTYYGUUJMG-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 47.1 nM (pChEMBL 7.329999923706055)
Descriptors: MW 340.38, ALogP 2.8, HBA 7, HBD 2, PSA 105.51, QED 0.75
Compound (SMILES): COc1cc2c(cc1CO)nc(-c1nccs1)n2-c1ccc2c(N)nc(N)nc2c1
InChIKey: AKOLUXJGSSGNIO-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition Assay: Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).
Measurement: Ki = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 419.47, ALogP 2.76, HBA 10, HBD 3, PSA 137.99, QED 0.4
Compound (SMILES): Cc1onc(-c2ccc(F)cc2)c1COc1ccc(C(=O)N2CCS(=O)(=O)CC2)cn1
InChIKey: VCGRFBXVSFAGGA-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Binding affinity to GABA-A alpha1 (unknown origin)
Measurement: Ki = 985 nM (pChEMBL 6.010000228881836)
Descriptors: MW 445.47, ALogP 2.63, HBA 7, HBD 0, PSA 102.6, QED 0.59
Compound (SMILES): Cc1onc(-c2cccnc2)c1COc1ccc(C(=O)NC2CCOCC2)cn1
InChIKey: QNWRGRATEXLYQY-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Radioligand Binding Assay: Radioligand binding assays were carried out in a volume of 200 mL (96-well plates) which contained 100 mL of cell memebranes, [3H]flumazenil at a concentration of 1 nM for α1, α2, α3 subunits and 0.5 nM for α5 subunits and the test compound in the range of 10-10−3x10−6 M. Nonspecific binding was defined by 10−5 M diazepam and typically represented less than 5% of the total binding. Assays were incubated to equilibrium for 1 hour at 4 C. and harvested onto GF/C uni-filters (Packard) by filtration using a Packard harvester and washing with ice-cold wash buffer (50 mM Tris; pH 7.5). After drying, filter-retained radioactivity was detected by liquid scintillation counting.
Measurement: Ki = 27.9 nM (pChEMBL 7.550000190734863)
Descriptors: MW 394.43, ALogP 2.93, HBA 7, HBD 1, PSA 99.37, QED 0.69
Compound (SMILES): Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)NC2CC(OCc3ccccc3)C2)cn1
InChIKey: WOXGCAVUJHNRNQ-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Radioligand Binding Assay: Radioligand binding assays were carried out in a volume of 200 mL (96-well plates) which contained 100 mL of cell memebranes, [3H]flumazenil at a concentration of 1 nM for α1, α2, α3 subunits and 0.5 nM for α5 subunits and the test compound in the range of 10-10−3x10−6 M. Nonspecific binding was defined by 10−5 M diazepam and typically represented less than 5% of the total binding. Assays were incubated to equilibrium for 1 hour at 4 C. and harvested onto GF/C uni-filters (Packard) by filtration using a Packard harvester and washing with ice-cold wash buffer (50 mM Tris; pH 7.5). After drying, filter-retained radioactivity was detected by liquid scintillation counting.
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 469.54, ALogP 5.1, HBA 6, HBD 1, PSA 86.48, QED 0.37
Compound (SMILES): Cc1ccc(-c2noc(C)c2COc2ccc(C(=O)NC3CCOCC3)cn2)cc1
InChIKey: VCAOZNYTIATHLZ-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Radioligand Binding Assay: Radioligand binding assays were carried out in a volume of 200 mL (96-well plates) which contained 100 mL of cell memebranes, [3H]flumazenil at a concentration of 1 nM for α1, α2, α3 subunits and 0.5 nM for α5 subunits and the test compound in the range of 10-10−3x10−6 M. Nonspecific binding was defined by 10−5 M diazepam and typically represented less than 5% of the total binding. Assays were incubated to equilibrium for 1 hour at 4 C. and harvested onto GF/C uni-filters (Packard) by filtration using a Packard harvester and washing with ice-cold wash buffer (50 mM Tris; pH 7.5). After drying, filter-retained radioactivity was detected by liquid scintillation counting.
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 407.47, ALogP 3.84, HBA 6, HBD 1, PSA 86.48, QED 0.67
Compound (SMILES): Cc1onc(-c2ccccn2)c1COc1ccc(C(=O)NC2CCOCC2)cn1
InChIKey: RBJYKFLLCXRSGC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Radioligand Binding Assay: Radioligand binding assays were carried out in a volume of 200 mL (96-well plates) which contained 100 mL of cell memebranes, [3H]flumazenil at a concentration of 1 nM for α1, α2, α3 subunits and 0.5 nM for α5 subunits and the test compound in the range of 10-10−3x10−6 M. Nonspecific binding was defined by 10−5 M diazepam and typically represented less than 5% of the total binding. Assays were incubated to equilibrium for 1 hour at 4 C. and harvested onto GF/C uni-filters (Packard) by filtration using a Packard harvester and washing with ice-cold wash buffer (50 mM Tris; pH 7.5). After drying, filter-retained radioactivity was detected by liquid scintillation counting.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 394.43, ALogP 2.93, HBA 7, HBD 1, PSA 99.37, QED 0.69
Compound (SMILES): Cn1cc(-c2cc(OCC(=O)N3CC(CO)C3)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: XTCFYLMJVKMCKF-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 473.45, ALogP 2.7, HBA 6, HBD 2, PSA 87.82, QED 0.6
Compound (SMILES): Cn1cc(-c2cc(OCCCC(=O)O)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: MLQBSJLQJIDSTD-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 432.4, ALogP 4.11, HBA 5, HBD 2, PSA 84.58, QED 0.57
Compound (SMILES): COC(=O)COc1cc(Br)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: XNAWHPNAHWCHFR-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 2719 nM (pChEMBL 5.570000171661377)
Descriptors: MW 417.18, ALogP 3.78, HBA 4, HBD 1, PSA 55.76, QED 0.77
Compound (SMILES): COC(=O)c1cc(Br)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: DKEVWCXRSMFEOF-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 387.15, ALogP 4.01, HBA 3, HBD 1, PSA 46.53, QED 0.75
Compound (SMILES): O=C(c1cc(-c2cnn(CCO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2)N1CCCC1
InChIKey: JHLHDHLUOOLDCK-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 457.45, ALogP 3.56, HBA 5, HBD 2, PSA 78.59, QED 0.63
Compound (SMILES): O=C(O)CCCOc1cc(Cl)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: LQPYVMZXAKJSNL-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 386.75, ALogP 4.36, HBA 3, HBD 2, PSA 66.76, QED 0.75
Compound (SMILES): COC(=O)COc1cc(Cl)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: BFROUFDSZGLRCL-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 251 nM (pChEMBL 6.599999904632568)
Descriptors: MW 372.73, ALogP 3.67, HBA 4, HBD 1, PSA 55.76, QED 0.84
Compound (SMILES): Cc1cc(-c2cnn(CCO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: YEUDACDOZNWCHD-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 374.36, ALogP 3.63, HBA 4, HBD 2, PSA 58.28, QED 0.74
Compound (SMILES): OCCn1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: ATVQODSMTYLUGV-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 378.33, ALogP 3.46, HBA 4, HBD 2, PSA 58.28, QED 0.69
Compound (SMILES): Cc1cc(-c2cnn(CC(N)=O)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: ATFQWTQFMRQWII-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 387.36, ALogP 3.12, HBA 4, HBD 2, PSA 81.14, QED 0.72
Compound (SMILES): O=C(O)CCCOc1cc(-c2cncnc2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: QHOUXBOAHUBGDQ-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 430.38, ALogP 4.17, HBA 5, HBD 2, PSA 92.54, QED 0.57
Compound (SMILES): CNC(=O)Cn1cc(-c2cc(C)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: DYUJQAQUBJQGIK-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 401.39, ALogP 3.38, HBA 4, HBD 2, PSA 67.15, QED 0.71
Compound (SMILES): CNC(=O)Cn1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: ZBEIYCPTUVQPKX-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 405.35, ALogP 3.21, HBA 4, HBD 2, PSA 67.15, QED 0.66
Compound (SMILES): Cc1cc(Cl)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: FLHRCPUVQJYYLW-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 3330 nM (pChEMBL 5.480000019073486)
Descriptors: MW 298.69, ALogP 4.43, HBA 1, HBD 1, PSA 20.23, QED 0.76
Compound (SMILES): OC1(C(F)(F)F)c2ccccc2-c2c(Cl)cc(F)cc21
InChIKey: XSLCFFOMHATYNA-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 397 nM (pChEMBL 6.400000095367432)
Descriptors: MW 302.65, ALogP 4.26, HBA 1, HBD 1, PSA 20.23, QED 0.72
Compound (SMILES): CCn1cc(-c2cc(C(N)=O)c3c(c2)C(O)(C(F)(F)F)c2ccccc2-3)cn1
InChIKey: LMOZOXYYIHMKOX-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 387.36, ALogP 3.45, HBA 4, HBD 2, PSA 81.14, QED 0.72
Compound (SMILES): COC(=O)c1cc(Cl)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: JCEKEIDOLNOUNU-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 342.7, ALogP 3.91, HBA 3, HBD 1, PSA 46.53, QED 0.8
Compound (SMILES): CCn1cc(-c2cc(CO)c3c(c2)C(O)(C(F)(F)F)c2ccccc2-3)cn1
InChIKey: AWJWYRFYSCGZBT-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 374.36, ALogP 3.84, HBA 4, HBD 2, PSA 58.28, QED 0.73
Compound (SMILES): CC(C)(C)Cn1cc(-c2cc(C(N)=O)c3c(c2)C(O)(C(F)(F)F)c2ccccc2-3)cn1
InChIKey: WNQDCKNQPGPVJH-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 429.44, ALogP 4.47, HBA 4, HBD 2, PSA 81.14, QED 0.64
Compound (SMILES): CC(C)Cc1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: JKRDTWYOUFVNHP-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 446.47, ALogP 4.05, HBA 5, HBD 3, PSA 78.51, QED 0.53
Compound (SMILES): CC(C)(C)Cn1cc(-c2cc(CO)c3c(c2)C(O)(C(F)(F)F)c2ccccc2-3)cn1
InChIKey: PTOAOEQLXBBCMP-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 416.44, ALogP 4.87, HBA 4, HBD 2, PSA 58.28, QED 0.64
Compound (SMILES): NC(=O)c1cc(-c2cnn(CC3CCCCC3)c2)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: ADQPEHBIUNFIJT-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 455.48, ALogP 5.01, HBA 4, HBD 2, PSA 81.14, QED 0.58
Compound (SMILES): CC(C)(C)CCc1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: FTPGWOJNMIQMNA-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 474.52, ALogP 4.83, HBA 5, HBD 3, PSA 78.51, QED 0.48
Compound (SMILES): COCCNC(=N)NCCCCN
InChIKey: SJQJFADASWPDIQ-UHFFFAOYSA-N
Target: N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94760
Assay: In Vitro HPLC Assay: This assay was used to determine the inhibiting effect of the inhibitors in a concentration of 1 mM. A standard incubation mixture consisted of 75 μl of 50 mM potassium phosphate buffer pH 7.4 and contained NMMA in a concentration of 200 μM. The inhibitors were used in final concentrations of 1 mM. By adding 2 μg of hDDAH-1, the reaction was started and the samples were incubated for 30 minutes at 37° C. in, a shaking water bath. The reaction was then stopped by adding 75 μl of acetonitrile, the samples were shaken for 5′ minutes and centrifuged (12,000 g, 5 min). The supernatant was added to the HPLC.
Measurement: IC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 188.27, ALogP -0.51, HBA 3, HBD 4, PSA 83.16, QED 0.25
Compound (SMILES): NC(=O)C(N[C@H]1CC[C@H](c2c[nH]c3ccccc32)CC1)C1CCN(C(=O)/C=C/c2cc(F)cc(F)c2)CC1
InChIKey: IVUXLLAISPCXRU-GNVGAZDYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Binding Assay: MCP-1 Receptor Binding Assay in THP-1 Cells Human monocytic cell line THP-1 cells were obtained from American Type Culture Collection (Manassas, Va., USA). The THP-1 cells were grown in RPMI-1640 (RPMI: Roswell Park Memorial Institute Medium-cell culture growth media) supplemented with 10% fetal bovine serum in a humidified 5% CO2 atmosphere at 37 C. The cell density was maintained between 0.5x106 cells/mL.THP-1 (cells were incubated with 0.5 nM 125I labeled MCP-1 (Perkin-Elmer Life Sciences, Inc. Boston, Mass.) in the presence of varying concentrations of either unlabeled MCP-1 (R & D Systems, Minneapolis, Minn.) or test compound for 2 hours at 30 C. in a 96 well plate. Cells were then harvested onto a filter plate, dried, and 20 uL of Microscint 20 was added to each well. Plates were counted in a TopCount NXT, Microplate Scintillation & Luminescence Counter (Perkin-Elmer Life Sciences, Inc. Boston, Mass.).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 520.62, ALogP 4.87, HBA 3, HBD 3, PSA 91.22, QED 0.39
Compound (SMILES): NC(=O)C(NC1CCC(c2c[nH]c3ccccc23)CC1)C1CCN(C(=O)Nc2ccc(Cl)c(Cl)c2)CC1
InChIKey: BGTCXGXSKWHLPW-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Binding Assay: MCP-1 Receptor Binding Assay in THP-1 Cells Human monocytic cell line THP-1 cells were obtained from American Type Culture Collection (Manassas, Va., USA). The THP-1 cells were grown in RPMI-1640 (RPMI: Roswell Park Memorial Institute Medium-cell culture growth media) supplemented with 10% fetal bovine serum in a humidified 5% CO2 atmosphere at 37 C. The cell density was maintained between 0.5x106 cells/mL.THP-1 (cells were incubated with 0.5 nM 125I labeled MCP-1 (Perkin-Elmer Life Sciences, Inc. Boston, Mass.) in the presence of varying concentrations of either unlabeled MCP-1 (R & D Systems, Minneapolis, Minn.) or test compound for 2 hours at 30 C. in a 96 well plate. Cells were then harvested onto a filter plate, dried, and 20 uL of Microscint 20 was added to each well. Plates were counted in a TopCount NXT, Microplate Scintillation & Luminescence Counter (Perkin-Elmer Life Sciences, Inc. Boston, Mass.).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 542.51, ALogP 5.89, HBA 3, HBD 4, PSA 103.25, QED 0.31
Compound (SMILES): NC(=O)C(N[C@H]1CC[C@H](c2c[nH]c3ccccc32)CC1)C1CCN(C(=O)/C=C/c2cc(F)c(F)c(F)c2)CC1
InChIKey: PDJAYZAJEHUMDM-YSVISZEVSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Binding Assay: MCP-1 Receptor Binding Assay in THP-1 Cells Human monocytic cell line THP-1 cells were obtained from American Type Culture Collection (Manassas, Va., USA). The THP-1 cells were grown in RPMI-1640 (RPMI: Roswell Park Memorial Institute Medium-cell culture growth media) supplemented with 10% fetal bovine serum in a humidified 5% CO2 atmosphere at 37 C. The cell density was maintained between 0.5x106 cells/mL.THP-1 (cells were incubated with 0.5 nM 125I labeled MCP-1 (Perkin-Elmer Life Sciences, Inc. Boston, Mass.) in the presence of varying concentrations of either unlabeled MCP-1 (R & D Systems, Minneapolis, Minn.) or test compound for 2 hours at 30 C. in a 96 well plate. Cells were then harvested onto a filter plate, dried, and 20 uL of Microscint 20 was added to each well. Plates were counted in a TopCount NXT, Microplate Scintillation & Luminescence Counter (Perkin-Elmer Life Sciences, Inc. Boston, Mass.).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 538.61, ALogP 5.01, HBA 3, HBD 3, PSA 91.22, QED 0.29