lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=c1ccc2c(-c3cnc(-c4cccnc4)s3)n[nH]c2[nH]1
InChIKey: JCIZDZAGSUATFA-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P20831
Assay: Inhibition of Staphylococcus aureus DNA gyrase ATPase activity using pBR322 DNA as substrate after 30 mins by fluorescence polarization assay
Measurement: IC50 = 265 nM (pChEMBL 6.579999923706055)
Descriptors: MW 295.33, ALogP 2.44, HBA 5, HBD 2, PSA 87.32, QED 0.59
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPS1
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPV5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU7
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU5
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccccc1
InChIKey: QXQOBCBJOCQFRK-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 507.63, ALogP 5.77, HBA 6, HBD 1, PSA 67.71, QED 0.27
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: JEEVMYLVUPBCFP-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccccc1
InChIKey: DZMUNSHMBCIBDH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 559.71, ALogP 6.88, HBA 6, HBD 1, PSA 67.71, QED 0.16
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1cccc(Br)c1
InChIKey: VBVMGRCNUWHODZ-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: TXZGGVBUNOVBHL-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 638.61, ALogP 7.65, HBA 6, HBD 1, PSA 67.71, QED 0.13
Compound (SMILES): C=CCCOc1nc2ccccc2cc1C(c1cc2ccccc2nc1OCCC=C)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: KNMXVWXMVVIKDE-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 666.66, ALogP 8.43, HBA 6, HBD 1, PSA 67.71, QED 0.09
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc2ccccc2c1
InChIKey: IXLSBDXBCUSOJH-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1ccc(Br)cc1
InChIKey: QDRJSIIKIUXVRU-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 586.53, ALogP 6.53, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): COc1nc2ccccc2cc1C(c1cc2ccccc2nc1OC)C(O)(CCN(C)C)c1cccc2ccccc12
InChIKey: FSIFTUHBPHJAAD-UHFFFAOYSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 557.69, ALogP 6.92, HBA 6, HBD 1, PSA 67.71, QED 0.21
Compound (SMILES): CN(C)CCC(O)(c1cccc(Br)c1)C1c2cc3ccccc3nc2OCC/C=C\CCOc2nc3ccccc3cc21
InChIKey: GHGVFXRKINKBLR-ARJAWSKDSA-N
Target: ATP synthase (PROTEIN COMPLEX), Mycobacterium tuberculosis
UniProt: P9WPU9
Assay: Inhibition of Mycobacterium tuberculosis ATP synthase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 638.61, ALogP 7.62, HBA 6, HBD 1, PSA 67.71, QED 0.2
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(CN4CC[C@@H](F)C4)nc(C(F)(F)F)n3)CC2)C1
InChIKey: NYQGENCZPKOZNT-HXUWFJFHSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 637.65, ALogP 3.4, HBA 10, HBD 1, PSA 135.75, QED 0.3
Compound (SMILES): N=C(N)N/N=C/c1ccc(-c2cccc(/C=N/NC(=N)N)c2)cc1
InChIKey: ASAFZZGZCWCAQQ-VGENTYGXSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of [3H]-dofetilide binding to human ERG expressed in HEK293 cell membranes measured after 1 hr by liquid scintillation counting method
Measurement: IC50 = 4660 nM (pChEMBL 5.329999923706055)
Descriptors: MW 322.38, ALogP 0.99, HBA 4, HBD 6, PSA 148.52, QED 0.28
Compound (SMILES): C[C@@H]1[C@H](c2cc(F)cc(F)c2F)C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N1CC(F)(F)F
InChIKey: OVTQOOXOGJZWCA-CJFQSICBSA-N
Target: Calcitonin gene-related peptide type 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16602
Assay: Receptor Functional Assay: Cells were resuspended in DMEM/F12 (Hyclone) supplemented with 1 g/L BSA and 300 μM isobutyl-methylxanthine. Cells were then plated in a 384-well plate (Proxiplate Plus 384; 509052761; Perkin-Elmer) at a density of 2,000 cells/well and incubated with antagonist for 30 min at 37° C. Human α-CGRP was then added to the cells at a final concentration of 1.2 nM and incubated an additional 20 min at 37° C. Following agonist stimulation, the cells were processed for cAMP determination using the two-step procedure according to the manufacturer's recommended protocol (HTRF cAMP dynamic 2 assay kit; 62AM4PEC; Cisbio). Raw data were transformed into concentration of cAMP using a standard curve then dose response curves were plotted and inflection point (IP) values were determined.
Measurement: Ki = 0.017 nM (pChEMBL 10.770000457763672)
Descriptors: MW 603.52, ALogP 3.95, HBA 5, HBD 2, PSA 104.29, QED 0.35
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(CN4CCC(F)(F)C4)nc(C(F)(F)F)n3)CC2)C1
InChIKey: DPIWJTAFNFKLQI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 655.64, ALogP 3.7, HBA 10, HBD 1, PSA 135.75, QED 0.3
Compound (SMILES): NCCOCCOc1ccc2nc(-c3cn(-c4ccc(O)cc4)nn3)ccc2c1
InChIKey: RXYWXMDDVUSFNI-UHFFFAOYSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Inhibition of Tautomerase Activity of Human MIF: Inhibition of the tautomerase activity of MIF was measured using 4-hydroxyphenyl pyruvic acid (HPP) as substrate, largely following previously reported protocols (Taylor et al., Biochemistry, 1999, 38, 7444-7452). HPP was dissolved in 0.5 M acetate buffer, pH 6.0 to a final concentration of 10 mM and incubated overnight at room temperature to allow equilibration of the keto and enol forms. MIF (6 μL) was premixed in 500 mM boric acid, pH 6.2 (142 μL) and transferred to a transparent U bottom 96-well plate to a final concentration of 50 nM MIF. At this concentration high signal-to-noise and linearity were observed after analysis of progress curves for enol production at different protein concentrations. Inhibitors were dissolved in DMSO to 10 mM and an initial screen was performed. For compounds that showed ca. 25% or greater inhibition at 10 μM, an inhibition constant, was measured.Compounds were placed into wells (2 μL) at 6 different concentrations and incubated for 30 minutes until the assay was started by addition of HPP (504) at two concentrations (1.0 and 2.5 mM). The negative control was MIF incubated with DMSO vehicle, which in all assays was 1% and did not influence tautomerase activity. MIF activity was monitored at 305 nm for formation of the borate-enol complex using an Infinite F500 plate reader (TECAN, Morrisville, N.C.) for 175 seconds. Calculation of initial velocities and the nonlinear regression analyses for the enzyme kinetics were repeated three times with the program Prism6 (GraphPad, La Jolla, Calif.).Data obtained for the Example compounds, obtained using the methods described in Example B, are provided in Table 3. Results are also included for a reference compound ISO-1 (Chang, K. F.; Al-Abed, Y. Bioorg. Med. Chem. Lett. 2006, 16, 3376-3379; Balachandran, S. et al. Bioorg. Med. Chem. Lett. 2009, 19, 4773-4776). X-ray crystal structures were obtained for complexes of 3a, 3b, and 3v (Examples 1, 2, and 21) with human MIF as described below in Example C, which confirm the binding of these inhibitors in the tautomerase active site.
Measurement: Ki = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 391.43, ALogP 2.54, HBA 8, HBD 2, PSA 108.31, QED 0.44
Compound (SMILES): CN(C)S(=O)(=O)N(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)CC1CCCCC1
InChIKey: YEVQRQIMHDCYHB-BKFWDETESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-DPN from guinea pig kappa opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 0.1995 nM (pChEMBL 9.699999809265137)
Descriptors: MW 476.69, ALogP 3.18, HBA 4, HBD 1, PSA 86.95, QED 0.59
Compound (SMILES): C[C@@H]1[C@H](c2c(F)ccc(F)c2F)C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N1CC(F)(F)F
InChIKey: QIVUCLWGARAQIO-OLIXTKCUSA-N
Target: Calcitonin-gene-related peptide receptor, CALCRL/RAMP1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16602
Assay: Antagonist activity at human CLR/RAMP1
Measurement: Ki = 0.015 nM (pChEMBL 10.819999694824219)
Descriptors: MW 603.52, ALogP 3.95, HBA 5, HBD 2, PSA 104.29, QED 0.35
Compound (SMILES): CNCc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)nc(C(F)(F)F)n1
InChIKey: YCUPPQQDENEPDE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 579.59, ALogP 2.58, HBA 10, HBD 2, PSA 144.54, QED 0.34
Compound (SMILES): Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: GCXKULANKFAPOX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(CN4CCCC4)nc(C(F)(F)F)n3)CC2)C1
InChIKey: LDFPVEUJEXWBDL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 619.66, ALogP 3.46, HBA 10, HBD 1, PSA 135.75, QED 0.33
Compound (SMILES): COc1ccc(S(=O)(=O)N(C(C)=O)c2ccccc2/C=C/c2cc[n+]([O-])cc2)cc1
InChIKey: OCKHRKSTDPOHEN-BQYQJAHWSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.48, ALogP 3.24, HBA 5, HBD 0, PSA 90.62, QED 0.45
Compound (SMILES): CCS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1.Cl
InChIKey: IYULGYKOHUAYCG-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd = 1 nM (pChEMBL 9)
Descriptors: MW 445.55, ALogP 1.37, HBA 8, HBD 3, PSA 133.55, QED 0.55
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: KSUDUUBCXJUFRL-SFHVURJKSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.51, ALogP 3.31, HBA 8, HBD 1, PSA 108.27, QED 0.46
Compound (SMILES): Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)NCc2cc(F)ccc2Oc2ccc3c(cnn3CCO)c2)cc1
InChIKey: LNMRSSIMGCDUTP-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 556.64, ALogP 6.07, HBA 7, HBD 3, PSA 106.23, QED 0.22
Compound (SMILES): Cc1nc2cc(-c3nn(C(C)C)c4ncnc(N)c34)ccc2o1
InChIKey: JUUFLLKHNYWHKP-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 308.35, ALogP 3.11, HBA 7, HBD 1, PSA 95.65, QED 0.61
Compound (SMILES): COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)c2c(N)ncnn2c1CN1CCOCC1
InChIKey: GZPJCJKUZPUFAL-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.54, ALogP 4.9, HBA 8, HBD 3, PSA 119.04, QED 0.26
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO.Cl
InChIKey: OOVTUOCTLAERQD-OJMBIDBESA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.85, ALogP 3.3, HBA 6, HBD 3, PSA 94.14, QED 0.62
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1Cl)c1nc2cccc(Cl)c2c(=O)n1-c1ccon1
InChIKey: ZGPGMFPDIVGLEN-ZETCQYMHSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length PI3K p110alpha/p85 alpha using PIP2/ATP as substrate after 30 mins by TR-FRET assay
Measurement: IC50 = 3538 nM (pChEMBL 5.449999809265137)
Descriptors: MW 433.26, ALogP 2.81, HBA 10, HBD 3, PSA 150.77, QED 0.44
Compound (SMILES): CC1(C)CCC(NCCCCN(C[C@H]2Cc3ccccc3CN2)[C@H]2CCCc3cccnc32)CC1
InChIKey: ONNXLKVJJQMNHD-WDYNHAJCSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at human CXCR4 in CCRF-CEM cells assessed as decrease in SDF-1alpha stimulated Ca2+ flux preincubated for 25 mins followed by SDF-1alpha addition measured for 90 secs by calcium dye-based fluorescence assay
Measurement: IC50 = 77.6 nM (pChEMBL 7.110000133514404)
Descriptors: MW 474.74, ALogP 5.81, HBA 4, HBD 2, PSA 40.19, QED 0.45
Compound (SMILES): CCN(Cc1cccs1)C(=O)COc1cc(C)ccc1O
InChIKey: SXBOAIXEVJQUFQ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 305.4, ALogP 3.19, HBA 4, HBD 1, PSA 49.77, QED 0.89
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(C#N)cc2)cc1N[C@@H](c1ccccc1)[C@H](O)CO
InChIKey: ATEXGOLHETZNBF-IRLDBZIGSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) using fluorescent labelled IPTSPITTTYFFFKKK peptide as substrate after 60 mins by caliper assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 417.47, ALogP 2.56, HBA 7, HBD 5, PSA 130.3, QED 0.38
Compound (SMILES): COc1ccn2c(c1)nc1c2c(=O)n(CC2CC2)c(=O)n1Cc1ccc(Br)cc1
InChIKey: WLRYWLSCMORCNI-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine A3 receptor expressed on CHO cell membranes after 2 hrs by scintillation spectrometry
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 455.31, ALogP 3.04, HBA 7, HBD 0, PSA 70.53, QED 0.46
Compound (SMILES): COc1cc(N(CC(=O)N2CCC(N)CC2)S(=O)(=O)c2ccc3c(c2)CCN3C(C)=O)ccc1-n1nc(C)cc1C
InChIKey: QZFOYXOHOOVFHO-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Binding affinity to LSD1 (unknown origin) by SPR analysis
Measurement: Kd > 100000 nM (pChEMBL 4)
Descriptors: MW 580.71, ALogP 2.55, HBA 8, HBD 1, PSA 131.07, QED 0.45
Compound (SMILES): CCNC(=O)Nc1cc2c(-c3ccncn3)ccc(C)c2cn1
InChIKey: BUTXZCVRZRLABV-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus N-terminal His6-tagged DNA gyrase subunit GyrA/GyrB supercoiling activity expressed in Escherichia coli BL21 (DE3) using relaxed pBR322 DNA as substrate after 1 hr by agarose gel electrophoresis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 307.36, ALogP 3.14, HBA 4, HBD 2, PSA 79.8, QED 0.78
Compound (SMILES): Nc1nccn2c(C34CCC(C(=O)O)(CC3)CC4)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
InChIKey: XTLSAZFITBCMQC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 550.54, ALogP 5.32, HBA 7, HBD 3, PSA 135.5, QED 0.31
Compound (SMILES): COc1ccc2c(c1)C(=O)N(c1ccc(-n3ccccc3=O)cc1)CN2C(=O)Cc1ccc(Cl)cc1
InChIKey: AVNLRDITXLDLJE-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human factor 10a using substrate S-2765 preincubated for 30 mins followed by substrate addition measured after 20 mins by micro plate reader method
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 499.95, ALogP 4.69, HBA 5, HBD 0, PSA 71.85, QED 0.4
Compound (SMILES): Cc1onc(-c2ccccc2)c1C(=O)Nc1ccc(-n2cnnn2)cc1
InChIKey: CYYSHNTUESRWKP-UHFFFAOYSA-N
Target: GATA4/NKX2-5 (PROTEIN COMPLEX), Mus musculus
UniProt: P42582
Assay: Inhibition of mouse GATA4/NKX2-5 transcriptional synergy expressed in African green monkey COS-1 cells measured after 30 hrs by dual luciferase reporter gene assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 346.35, ALogP 2.88, HBA 7, HBD 1, PSA 98.73, QED 0.61
Compound (SMILES): Nc1nccn2c([C@@H]3CCC[C@H](c4n[nH]c(=O)o4)C3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
InChIKey: LLQIDADXQLTRCN-SJORKVTESA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of 6-His-tagged recombinant full length BTK (unknown origin) expressed in baculovirus-transfected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 564.53, ALogP 4.76, HBA 9, HBD 3, PSA 157.09, QED 0.28
Compound (SMILES): CN(C)Cc1ccc(-c2cc(C#N)c(NCc3ccccc3)n3cnnc23)cc1
InChIKey: QLKBCENFIRCWBD-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: Inhibition of recombinant N-terminal GST-tagged EED (76 to 441 residues) (unknown origin) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIL assessed as reduction in SAH production using H3[21-44,K27Me0) peptide as substrate measured after 20 mins by LC/MS/MS method
Measurement: IC50 = 21800 nM (pChEMBL 4.659999847412109)
Descriptors: MW 382.47, ALogP 3.94, HBA 6, HBD 1, PSA 69.25, QED 0.55
Compound (SMILES): C[C@@H]1CN(C(=O)c2nc(Nc3cc(C4CC4)[nH]n3)c3cc(F)ccc3n2)CCN1
InChIKey: XDENYPBBMVGONB-LLVKDONJSA-N
Target: Serine/threonine-protein kinase PAK 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13153
Assay: Inhibition of human PAK1 kinase domain using coumarin and fluorescein-labeled ser/thr19 peptide as substrate preincubated for 15 mins followed by ATP addition measured after 60 mins by Z'-Lyte assay
Measurement: Ki = 503 nM (pChEMBL 6.300000190734863)
Descriptors: MW 395.44, ALogP 2.55, HBA 6, HBD 3, PSA 98.83, QED 0.63
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1NC(=O)C1(c2cc(NCCN(C)C)ncn2)CC1
InChIKey: CWRHQBPYFPUZLF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of recombinant human N-terminal GST-tagged BRAF catalytic domain (416 to 766 residues) V600E mutant expressed in baculovirus expression system using human His6-tagged MEK1 K97R mutant as substrate pretreated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter binding method
Measurement: IC50 = 68.2 nM (pChEMBL 7.170000076293945)
Descriptors: MW 561.01, ALogP 5.35, HBA 6, HBD 3, PSA 99.25, QED 0.33
Compound (SMILES): C[C@@H](c1ccc(F)cc1)n1nnc2cnc3ccc(-c4ccc(N5CCN(C)CC5)nc4)cc3c21
InChIKey: XWIGWRUXZIZMSL-SFHVURJKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in insect cells using RRRFRPASPLRGPPK peptide as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.55, ALogP 4.54, HBA 7, HBD 0, PSA 62.97, QED 0.39
Compound (SMILES): CN(C)c1nc2ccc(C(O)(c3ccncc3)c3cncn3C)cc2c(Cl)c1-c1ccccc1
InChIKey: SEJAMGYPDDPTHR-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of 1,8-ANS from recombinant human RORgammat LBD expressed in Escherichia coli BL21 (DE3) cells assessed as inhibition of co-activator SRC1 peptide recruitment by thermofluor assay
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 469.98, ALogP 5.03, HBA 6, HBD 1, PSA 67.07, QED 0.39
Compound (SMILES): COc1ccc2nc(S)n(-c3cccc(S(N)(=O)=O)c3)c(=O)c2c1
InChIKey: RKJNHTDIOSYCKU-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 3200 nM (pChEMBL 5.5)
Descriptors: MW 363.42, ALogP 1.33, HBA 7, HBD 2, PSA 104.28, QED 0.54
Compound (SMILES): COc1ccc(C2(C)CCCc3nc(SCc4c(F)cncc4F)n(-c4ccc(F)cc4)c32)cc1OC
InChIKey: FOLPXEFXCYPPQT-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at TGR5 in mouse STC1 cells assessed as increase in cAMP accumulation after 40 mins by mass spectrometric method
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 525.6, ALogP 6.64, HBA 6, HBD 0, PSA 49.17, QED 0.25