lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCc1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: SGQFOQDTNFEHFH-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 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 432.44, ALogP 3.81, HBA 5, HBD 3, PSA 78.51, QED 0.55
Compound (SMILES): CCc1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: SHWXPFHYAGUJHD-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 418.42, ALogP 3.42, HBA 5, HBD 3, PSA 78.51, QED 0.59
Compound (SMILES): CC(C)c1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: IYPZTKPCTOMGLM-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 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 432.44, ALogP 3.98, HBA 5, HBD 3, PSA 78.51, QED 0.57
Compound (SMILES): NC(=O)c1cc(CCCN2CCCC2=O)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: SEGSOHGKVMXOFC-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 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 418.42, ALogP 3.12, HBA 3, HBD 2, PSA 83.63, QED 0.78
Compound (SMILES): O=C1CCCN1CCCc1cc(CO)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: CPCCTTNWFGLSKW-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 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 405.42, ALogP 3.51, HBA 3, HBD 2, PSA 60.77, QED 0.8
Compound (SMILES): NC(=O)c1cc(-c2cncnc2)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: XSISOLYWTABXLA-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 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 371.32, ALogP 3.02, HBA 4, HBD 2, PSA 89.1, QED 0.72
Compound (SMILES): CC(C)(O)Cn1cc(-c2cc(CO)c3c(c2)C(O)(C(F)(F)F)c2ccccc2-3)cn1
InChIKey: IXXDAOWLXRTQQG-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 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 418.42, ALogP 3.59, HBA 5, HBD 3, PSA 78.51, QED 0.61
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 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 455.48, ALogP 5.01, HBA 4, HBD 2, PSA 81.14, QED 0.58
Compound (SMILES): Cc1cc(-c2cnn(CC(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: CTKLHGUNMOEXRQ-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 = 18 nM (pChEMBL 7.75)
Descriptors: MW 418.42, ALogP 3.24, HBA 5, HBD 3, PSA 78.51, QED 0.59
Compound (SMILES): CC(C)=Cc1cc(-c2cnn(C(CO)CO)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: QLFQBMDXKHYFGU-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 444.45, ALogP 4.28, HBA 5, HBD 3, PSA 78.51, QED 0.55
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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 474.52, ALogP 4.83, HBA 5, HBD 3, PSA 78.51, QED 0.48
Compound (SMILES): OCc1cc(-c2cnn(CC3CCCCC3)c2)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: NXCUOGIPGXSPKM-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 442.48, ALogP 5.4, HBA 4, HBD 2, PSA 58.28, QED 0.57
Compound (SMILES): N#Cc1ccc2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: OWXWZHUPQUNOQL-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 = 1443 nM (pChEMBL 5.840000152587891)
Descriptors: MW 275.23, ALogP 3.34, HBA 2, HBD 1, PSA 44.02, QED 0.8
Compound (SMILES): CC(CO)(CO)n1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: JXSCVVYWYGAHJC-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 422.38, ALogP 3.17, HBA 5, HBD 3, PSA 78.51, QED 0.56
Compound (SMILES): CC(C)(O)Cn1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: YODHNGOOSWAVEO-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 406.38, ALogP 4.24, HBA 4, HBD 2, PSA 58.28, QED 0.64
Compound (SMILES): OCC(CO)c1ncc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)o1
InChIKey: JKGNEFBIPIRXBM-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 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 409.33, ALogP 3.33, HBA 5, HBD 3, PSA 86.72, QED 0.58
Compound (SMILES): OCC(CO)c1noc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)n1
InChIKey: ZTGUEDVGPUIKDO-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 = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 410.32, ALogP 2.72, HBA 6, HBD 3, PSA 99.61, QED 0.57
Compound (SMILES): CC(C)(O)C(C)(C)n1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: GYPQXVMMXAYJFG-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 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 434.43, ALogP 4.97, HBA 4, HBD 2, PSA 58.28, QED 0.57
Compound (SMILES): Cc1cc(-c2cnn(CCCc3nn[nH]n3)c2)c2c(c1)C(O)(C(F)(F)F)c1ccccc1-2
InChIKey: LASGABFFNCGIDD-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 440.43, ALogP 3.78, HBA 6, HBD 2, PSA 92.51, QED 0.49
Compound (SMILES): CC(CO)(CO)n1cc(-c2cccc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: LQWWPUGVCMHMNI-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 404.39, ALogP 3.03, HBA 5, HBD 3, PSA 78.51, QED 0.62
Compound (SMILES): OCC(CO)(CO)n1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
InChIKey: ZRBSKAJTTXBPBY-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 438.38, ALogP 2.14, HBA 6, HBD 4, PSA 98.74, QED 0.46
Compound (SMILES): CCOc1ccc(Cc2cc3c(cc2Cl)OC[C@H]2C[C@H]2COC[C@H]2O[C@@H]3[C@H](O)[C@@H](O)[C@@H]2O)cc1
InChIKey: NWTCDPQRGHWQTK-KOZZFCAKSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 490.98, ALogP 2.9, HBA 7, HBD 3, PSA 97.61, QED 0.61
Compound (SMILES): CCOc1ccc(Cc2cc3c(cc2Cl)OC[C@@H]2C[C@@H]2COC[C@H]2O[C@@H]3[C@H](O)[C@@H](O)[C@@H]2O)cc1
InChIKey: NWTCDPQRGHWQTK-ZTLUSCJTSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition Assay: For sodium-dependent glucose transport assay, cells expressing hSGLT2 were seeded into a 96-well culture plate at a density of 5x104 cells/well in RPMI medium 1640 containing 10% fetal bovine serum. The cells were used 1 day after plating. They were incubated in pretreatment buffer (10 mM HEPES, 5 mM Tris, 140 mM choline chloride, 2 mM KCl, 1 mM CaCl2, and 1 mM MgCl2, pH 7.4) at 37 C. for 10 min. They were then incubated in uptake buffer (10 mM HEPES, 5 mM Tris, 140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, and 1 mM 14C-nonlabeled AMG pH 7.4) containing 14C-labeled AMG (8 uM) and the inventive compound or dimethyl sulfoxide (DMSO) vehicle at 37 C. for 2 h. Cells were washed twice with washing buffer (pretreatment buffer containing 10 mM AMG at room temperature) and then the radioactivity was measured using a liquid scintillation counter. IC50 was determined by nonlinear regression analysis using GraphPad PRISM [Katsuno, K. et al. J. Pharmacol. Exp. Ther. 2007, 320, 323-330].
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 490.98, ALogP 2.9, HBA 7, HBD 3, PSA 97.61, QED 0.61
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: Ki = 18000 nM (pChEMBL 4.75)
Descriptors: MW 188.27, ALogP -0.51, HBA 3, HBD 4, PSA 83.16, QED 0.25
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NCCCc1ccccc1
InChIKey: OKIVMGYKKNICMM-FYWRMAATSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 627 nM (pChEMBL 6.199999809265137)
Descriptors: MW 427.61, ALogP 4.68, HBA 5, HBD 3, PSA 64.6, QED 0.14
Compound (SMILES): CCCCCNc1cc(/C=C/C(=O)NO)ccc1SCCN(CC)CC
InChIKey: OVLUEOGUBUDCPK-ZRDIBKRKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 578 nM (pChEMBL 6.239999771118164)
Descriptors: MW 379.57, ALogP 4.24, HBA 5, HBD 3, PSA 64.6, QED 0.16
Compound (SMILES): CCCNc1cc(/C=C/C(=O)NO)ccc1SCCN(CC)CC
InChIKey: QSPYZPJWKSJGLE-CSKARUKUSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 653 nM (pChEMBL 6.179999828338623)
Descriptors: MW 351.52, ALogP 3.46, HBA 5, HBD 3, PSA 64.6, QED 0.25
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NC(C)=O
InChIKey: VOFHIAHUBREBSZ-VQHVLOKHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 357 nM (pChEMBL 6.449999809265137)
Descriptors: MW 351.47, ALogP 2.6, HBA 5, HBD 3, PSA 81.67, QED 0.28
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1[N+](=O)[O-]
InChIKey: NOCZCZOQQHGXOK-SOFGYWHQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 313 nM (pChEMBL 6.5)
Descriptors: MW 339.42, ALogP 2.55, HBA 6, HBD 2, PSA 95.71, QED 0.24
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NCc1ccccc1
InChIKey: SKUTVKKTLBSXRN-ACCUITESSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 399.56, ALogP 4.25, HBA 5, HBD 3, PSA 64.6, QED 0.23
Compound (SMILES): C=CCNc1cc(/C=C/C(=O)NO)ccc1SCCN(CC)CC
InChIKey: XGWZEJIDVVURML-CSKARUKUSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 349.5, ALogP 3.24, HBA 5, HBD 3, PSA 64.6, QED 0.19
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NC
InChIKey: KGKCXUYBOHEQQX-VQHVLOKHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 323.46, ALogP 2.68, HBA 5, HBD 3, PSA 64.6, QED 0.28
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1N
InChIKey: MDFHHPZAYBVIME-SOFGYWHQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 309.44, ALogP 2.22, HBA 5, HBD 3, PSA 78.59, QED 0.23
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NS(=O)(=O)c1ccc(C)cc1
InChIKey: QDXCIQUXJRPREV-UKTHLTGXSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 463.63, ALogP 3.75, HBA 6, HBD 3, PSA 98.74, QED 0.2
Compound (SMILES): C=CCCCNc1cc(/C=C/C(=O)NO)ccc1SCCN(CC)CC
InChIKey: JEMQNEUAVCLVRL-ZRDIBKRKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 377.55, ALogP 4.02, HBA 5, HBD 3, PSA 64.6, QED 0.12
Compound (SMILES): CCN(CC)CCSc1ccc(/C=C/C(=O)NO)cc1NC(=O)C(Cl)Cl
InChIKey: FDYCCWDPHWOAPH-SOFGYWHQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: BIOMOL Fluorescent-Based HDAC Assay: The BIOMOL fluorescent-based HDAC activity assay has been applied in In vitro HDACi assay for determination of IC50 values of the compounds of this invention. The assay has been carried out in white 96 well formats according to the BIOMOL's method. In order to optimize the experiment conditions and optinal, the exact concentration range of the Deacetylated Standard (biomol, KI-142) that will vary depending on the flurimeter model, the gain setting and the exact excitation and emission wavelengths used. We recommend diluting some of the standard to a relatively low concentration with Assay Buffer (an appropriate series of Deacetylated Standard dilutions from 20 uM to 0.3125 uM), and Assay Buffer as a time zero to a set of wells on the microtiter plate. Experimental to samples (five dilute groups: 100 uM, 20 uM, 4 uM, 0.8 uM, 0.16 uM) should be compared to a time zero.
Measurement: IC50 = 313 nM (pChEMBL 6.5)
Descriptors: MW 420.36, ALogP 3.38, HBA 5, HBD 3, PSA 81.67, QED 0.18
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 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 520.62, ALogP 4.87, HBA 3, HBD 3, PSA 91.22, QED 0.39