lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C1Cc2ccccc2C1)C(=O)N[C@H](/C=C/S(C)(=O)=O)CC(=O)O
InChIKey: UPNDCXMMARFRPM-RNDACTHJSA-N
Target: Caspase-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P55210
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 714.79, ALogP 1.31, HBA 9, HBD 6, PSA 234.37, QED 0.14
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(C)(=O)=O)CC(=O)O
InChIKey: SXHHMPCBHMVLQW-UFEMVYOUSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 3330 nM (pChEMBL 5.478000164031982)
Descriptors: MW 670.69, ALogP -0.24, HBA 10, HBD 7, PSA 271.67, QED 0.1
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](Cc1ccc2ccccc2n1)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(=O)(=O)c1ccccc1)CC(=O)O
InChIKey: CPFXCSLAAJOPLW-NQKMJEHBSA-N
Target: Caspase-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42574
Assay: Inhibition Assay: To test the efficacy of caspase-3 inhibitors at the cellular level, the ability of selected compounds to inhibit the proteolytic cleavage of PARP (poly ADP-ribose polymerase) was evaluated in live Hela cells.Briefly, in this assay Hela cells are seeded in 96 well plates and incubated for 4 hours with staurosporine, a well characterized inducer of apoptosis, alone or together with different concentrations of compound (50, 25, 10 and 3 uM). After formaldehyde-based fixation, the cells are stained with a fluorescein-labeled anti-cleaved PARP antibody (Cell signaling, Cat#: 9547) and counterstained with Hoechst33342 (Invitrogen, Cat#: H3570) to mark all nuclei.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 801.88, ALogP 3.12, HBA 10, HBD 6, PSA 247.26, QED 0.08
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](Cc1ccc2ccccc2n1)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(=O)(=O)Oc1ccccc1)CC(=O)O
InChIKey: FZAVLWDWOZHIBJ-NQKMJEHBSA-N
Target: Caspase-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P55210
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 817.87, ALogP 3.05, HBA 11, HBD 6, PSA 256.49, QED 0.07
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](Cc1ccc2ccccc2n1)NC(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(=O)(=O)N1CCOCC1)CC(=O)OC(C)(C)C
InChIKey: GVTFGSNZLNVNEH-GSIBMNKWSA-N
Target: Caspase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P55211
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 3330 nM (pChEMBL 5.478000164031982)
Descriptors: MW 923.1, ALogP 3.82, HBA 13, HBD 4, PSA 237.73, QED 0.1
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C1Cc2ccccc2C1)C(=O)N[C@H](/C=C/S(=O)(=O)C(C)C)CC(=O)O
InChIKey: XEWZRZSJGJZHSY-QVZFUARWSA-N
Target: Caspase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P55211
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 3330 nM (pChEMBL 5.478000164031982)
Descriptors: MW 742.85, ALogP 2.09, HBA 9, HBD 6, PSA 234.37, QED 0.13
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)c1ccccc1)C(=O)N[C@H](/C=C/S(=O)(=O)c1ccccc1)CC(=O)O
InChIKey: XNKWERCTKCULEN-OPZJAVCUSA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 3330 nM (pChEMBL 5.478000164031982)
Descriptors: MW 736.8, ALogP 2.7, HBA 9, HBD 6, PSA 234.37, QED 0.11
Compound (SMILES): COc1cc(F)ccc1-c1ccnc(NC(=O)[C@H]2CCC[C@@H](NC(C)=O)C2)c1
InChIKey: QNWXRLPZIFMTBK-DOTOQJQBSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: In Vitro Kinase Inhibition Assay: In vitro kinase assay analysis may be performed using standard techniques described in the art. These techniques are also used by commercial services providers in order to offer in vitro kinase activity assay services, e.g. the assays offered by Millipore Inc. (worldwide website www(dot)millipore.com), ProQinase GmbH (worldwide website www(dot)proqinase.de) and others. All kinase assays were performed in 96-well FlashPlates from Perkin Elmer/NEN (Boston, Mass., USA) in a 50ul reaction volume. The reaction mixture was pipetted in four steps in the following order: 20ul of assay buffer (standard buffer),5ul of ATP solution (in H2O, 5 ul of test compound (in 10% DMSO), 10ul of substrate/10ul of enzyme solution (premixed)The assay for all enzymes contained 60 mM HEPES-NaOH (pH 7.5), 3 mM MgCl2, 3 mM MnCl2, 3uM Na-Orthovanadate, 1.2 mM DTT, 50 ug/ml PEG2000, 1 uM [33P]-ATP (approx. 5x1005 cpm per well).
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.44, ALogP 3.53, HBA 4, HBD 2, PSA 80.32, QED 0.83
Compound (SMILES): COc1cc(F)ccc1-c1ccnc(NC(=O)C2CCC(NC(C)=O)C2)c1
InChIKey: FUMJKSZLZJFCAQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: In Vitro Kinase Inhibition Assay: In vitro kinase assay analysis may be performed using standard techniques described in the art. These techniques are also used by commercial services providers in order to offer in vitro kinase activity assay services, e.g. the assays offered by Millipore Inc. (worldwide website www(dot)millipore.com), ProQinase GmbH (worldwide website www(dot)proqinase.de) and others. All kinase assays were performed in 96-well FlashPlates from Perkin Elmer/NEN (Boston, Mass., USA) in a 50ul reaction volume. The reaction mixture was pipetted in four steps in the following order: 20ul of assay buffer (standard buffer),5ul of ATP solution (in H2O, 5 ul of test compound (in 10% DMSO), 10ul of substrate/10ul of enzyme solution (premixed)The assay for all enzymes contained 60 mM HEPES-NaOH (pH 7.5), 3 mM MgCl2, 3 mM MnCl2, 3uM Na-Orthovanadate, 1.2 mM DTT, 50 ug/ml PEG2000, 1 uM [33P]-ATP (approx. 5x1005 cpm per well).
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 371.41, ALogP 3.14, HBA 4, HBD 2, PSA 80.32, QED 0.85
Compound (SMILES): COc1ccc(COc2ccc(Cn3c(N)nc4cc(-c5cnn(C)c5)ccc43)cc2OC)cc1
InChIKey: CXVBPWYIUWZVJO-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition Assay: Reagents and consumables were purchased from Sigma Aldrich, Carna Biosciences, or Caliper Life Sciences. All assay reaction conditions for IC50 determinations were within the linear range with respect to time and enzyme concentration. In a 384 well polypropylene plate, c-FMS (0.14 nM, Carna 08-155) was pre-incubated in a 100 mM Hepes-NaOH pH 7.5 buffer containing 0.01% Triton X-100, 10 mM MgCl2, 0.1% BSA, 1 mM DTT, 10 uM sodium orthovanadate and 10 uM beta-glycerophosphate and compound with a concentration of 2.5% DMSO for 15 minutes at room temperature. The reaction was initiated with an equal volume of peptide substrate (Caliper Life Sciences catalog no. 760430) and ATP in the aforementioned buffer. The final concentrations in the reaction were 70 pM c-FMS, 1.5 uM peptide substrate and 500 uM ATP (ATP Km). The reaction was incubated at room temperature for 120 minutes and terminated with a buffer containing excess EDTA (100 mM Hepes-NaOH pH 7.5, 0.02% Brij, 0.1% CR-3.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 469.55, ALogP 4.66, HBA 8, HBD 1, PSA 89.35, QED 0.36
Compound (SMILES): COc1ccc(COc2ccc(Cn3c(N)nc4cc(-c5cnn(C)c5)cnc43)cc2OC)cc1
InChIKey: HVRWZFQFSQUILC-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition Assay: Reagents and consumables were purchased from Sigma Aldrich, Carna Biosciences, or Caliper Life Sciences. All assay reaction conditions for IC50 determinations were within the linear range with respect to time and enzyme concentration. In a 384 well polypropylene plate, c-FMS (0.14 nM, Carna 08-155) was pre-incubated in a 100 mM Hepes-NaOH pH 7.5 buffer containing 0.01% Triton X-100, 10 mM MgCl2, 0.1% BSA, 1 mM DTT, 10 uM sodium orthovanadate and 10 uM beta-glycerophosphate and compound with a concentration of 2.5% DMSO for 15 minutes at room temperature. The reaction was initiated with an equal volume of peptide substrate (Caliper Life Sciences catalog no. 760430) and ATP in the aforementioned buffer. The final concentrations in the reaction were 70 pM c-FMS, 1.5 uM peptide substrate and 500 uM ATP (ATP Km). The reaction was incubated at room temperature for 120 minutes and terminated with a buffer containing excess EDTA (100 mM Hepes-NaOH pH 7.5, 0.02% Brij, 0.1% CR-3.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 470.53, ALogP 4.06, HBA 9, HBD 1, PSA 102.24, QED 0.36
Compound (SMILES): COc1ccc(COc2ccc(Cn3cnc4cc(N5CCN(C)CC5)cnc43)cc2OC)cn1
InChIKey: IIJKGBMUSGQZJO-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition Assay: Reagents and consumables were purchased from Sigma Aldrich, Carna Biosciences, or Caliper Life Sciences. All assay reaction conditions for IC50 determinations were within the linear range with respect to time and enzyme concentration. In a 384 well polypropylene plate, TrkB (0.6 nM, Carna 08-187) was pre-incubated in a 100 mM Hepes-NaOH pH 7.5 buffer containing 0.01% Triton X-100, 10 mM MgCl2, 0.1% BSA, 1 mM DTT, 10 uM sodium orthovanadate and 10 μM beta-glycerophosphate and compound with a concentration of 2.5% DMSO for 15 minutes at room temperature. The reaction was initiated with an equal volume of peptide substrate (Caliper Life Sciences catalog no. 760430) and ATP in the aforementioned buffer. The final concentrations in the reaction were 300 pM TrkB, 1.5 μM peptide substrate and 70 μM ATP (ATP Km). The reaction was incubated at room temperature for 180 minutes and terminated with a buffer containing excess EDTA (100 mM Hepes-NaOH pH 7.5, 0.02% Brij, 0.1% CR-3, 0.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 474.57, ALogP 3.22, HBA 9, HBD 0, PSA 77.77, QED 0.39
Compound (SMILES): CC(C)[C@@H]1c2nc3cc(CO)c(S(C)(=O)=O)cc3n2CCN1c1ncc(C(C)(C)O)c(C(F)(F)F)n1
InChIKey: IUMMDSSCERZSTJ-GOSISDBHSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 527.57, ALogP 3.19, HBA 9, HBD 2, PSA 121.44, QED 0.52
Compound (SMILES): CC(C)[C@H]1c2nc3cc(CO)c(S(C)(=O)=O)cc3n2CCN1c1ncc(C(C)(C)O)c(C(F)(F)F)n1
InChIKey: IUMMDSSCERZSTJ-SFHVURJKSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 712 nM (pChEMBL 6.150000095367432)
Descriptors: MW 527.57, ALogP 3.19, HBA 9, HBD 2, PSA 121.44, QED 0.52
Compound (SMILES): CC(O)c1cnc(N2CCn3c(nc4cc(CO)c(S(C)(=O)=O)cc43)[C@@H]2C(C)C)nc1C(F)(F)F
InChIKey: WAZXSGZGKNWHSO-ZJFPTPTDSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 513.54, ALogP 3.01, HBA 9, HBD 2, PSA 121.44, QED 0.53
Compound (SMILES): CC(O)c1cnc(N2CCn3c(nc4cc(CO)c(S(C)(=O)=O)cc43)[C@H]2C(C)C)nc1C(F)(F)F
InChIKey: WAZXSGZGKNWHSO-VMHBGOFLSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 513.54, ALogP 3.01, HBA 9, HBD 2, PSA 121.44, QED 0.53
Compound (SMILES): CCC(O)c1cnc(N2CCn3c(nc4cc(CO)c(S(C)(=O)=O)cc43)[C@@H]2C(C)C)nc1C(F)(F)F
InChIKey: OEALQQJYLLGJFL-NNBQYGFHSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 527.57, ALogP 3.4, HBA 9, HBD 2, PSA 121.44, QED 0.5
Compound (SMILES): CCC(O)c1cnc(N2CCn3c(nc4cc(CO)c(S(C)(=O)=O)cc43)[C@H]2C(C)C)nc1C(F)(F)F
InChIKey: OEALQQJYLLGJFL-WHCXFUJUSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 527.57, ALogP 3.4, HBA 9, HBD 2, PSA 121.44, QED 0.5
Compound (SMILES): CCCC(O)c1cnc(N2CCn3c(nc4cc(CO)c(S(C)(=O)=O)cc43)[C@H]2C(C)C)nc1C(F)(F)F
InChIKey: WZDFAJOVHXXHKS-ROPPNANJSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 541.6, ALogP 3.79, HBA 9, HBD 2, PSA 121.44, QED 0.46
Compound (SMILES): CC(C)[C@@H]1c2nc3cc(CO)c(S(C)(=O)=O)cc3n2CCN1c1ncc(C(N)=O)c(C(F)(F)F)n1
InChIKey: XZVKGPBWXMHCFG-MRXNPFEDSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 512.51, ALogP 2.06, HBA 9, HBD 2, PSA 144.3, QED 0.53
Compound (SMILES): CC(O)c1cnc(N2CCn3c(nc4ccc(S(C)(=O)=O)cc43)[C@H]2C(C)C)nc1C(F)(F)F
InChIKey: VGEORAURCJKCNM-RGUGMKFQSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]T0901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at room temperature.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 483.52, ALogP 3.52, HBA 8, HBD 1, PSA 101.21, QED 0.61
Compound (SMILES): COc1ncc(F)cc1CNc1ncc(Cc2c[nH]c3ncc(C)cc23)cn1
InChIKey: IITAGIUAJYXYRU-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 378.41, ALogP 3.41, HBA 6, HBD 2, PSA 88.61, QED 0.53
Compound (SMILES): COc1ccc(CNc2ccc(Cc3c[nH]c4ncc(C)cc34)c(F)n2)c(OC)n1
InChIKey: PYDGBRKMKPMMFU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 407.45, ALogP 4.02, HBA 6, HBD 2, PSA 84.95, QED 0.45
Compound (SMILES): Cc1cnc2[nH]cc(Cc3ccc(NCc4cccnc4F)nc3F)c2c1
InChIKey: ZPELTGPUSIGURF-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 365.39, ALogP 4.14, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1cnc2[nH]cc(Cc3ccc(NCc4ccnc(F)c4)nc3F)c2c1
InChIKey: WVCIKWIWVGCIOM-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Biochemical Assay: In one assay the biochemical activity IC50 values are determined with respect to inhibition of Fms kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested, dissolved in DMSO (1 uL), are added to a white 384-well plate (Costar #3705). Working stocks of Fms kinase (Invitrogen #PV3249), biotin-(E4Y)10 substrate (Upstate Biotech, Cat#12-440), and ATP (Sigma, Cat#A-3377) are prepared in 25 mM Hepes pH 7.5, 0.5 mM MgCl2, 2 mM MnCl2, 2 mM DTT, 0.01% BSA, and 0.01% Tween-20. All components are added to the 384-well plate for a final concentration of 1 ng/well Fms, 30 nM biotin-(E4Y)10 (Upstate Biotechnology) and 100 uM ATP in a volume of 20 uL. Each sample is at 5% DMSO. The plate is then incubated for 20 minutes at 30 C. Just before use, working stocks of donor and acceptor beads from the AlphaScreen PY20 Detection Kit (PerkinElmer, Cat#676601M) are prepared in 25 mM Hepes pH 7.5.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 365.39, ALogP 4.14, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1ccc(CNc2ccc(Cc3c[nH]c4ncc(C)cc34)c(F)n2)nc1
InChIKey: SYSOKYYRVIKDBZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 361.42, ALogP 4.31, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): CCS(=O)(=O)Nc1ccccc1CNc1ccc(Cc2c[nH]c3ncc(C)cc23)c(F)n1
InChIKey: ZGVRUEHWRJFEDB-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Biochemical Assay: In one assay the biochemical activity IC50 values are determined with respect to inhibition of c-Kit kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested are dissolved in DMSO to a concentration of 20 mM. These are diluted 30 uL into 120 uL of DMSO (4 mM) and 1 uL is added to an assay plate. These are then serially diluted 1:2 (50 uL to 100 uL DMSO) for a total of 8 points. Plates are prepared such that each kinase reaction is 20 uL in 1x kinase buffer (25 mM HEPES, pH 7.5, 2 mM MgCl2, 2 mM MnCl2, 0.01% Tween-20, 1 mM DTT, 0.01% BSA), 5% DMSO and 100 uM ATP. Substrate is 30 nM biotin-(E4Y)10 (Millipore). C-kit kinase (obtained from Millipore (#14-559) or is prepared as described in U.S. Patent Application Publication Number 2009/0076046, the disclosure of which is hereby incorporated by reference as it relates to this assay) is at 0.75 ng per sample.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 453.54, ALogP 4.37, HBA 5, HBD 3, PSA 99.77, QED 0.34
Compound (SMILES): Fc1cncc(CNc2ccc(Cc3c[nH]c4ncc(Cl)cc34)c(F)n2)c1
InChIKey: UFYPFASIUYPWBC-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.81, ALogP 4.49, HBA 4, HBD 2, PSA 66.49, QED 0.5
Compound (SMILES): COc1cnc2[nH]cc(Cc3ccc(NCc4cncc(F)c4)nc3F)c2c1
InChIKey: FHPWLAWTGBVVFI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.39, ALogP 3.84, HBA 5, HBD 2, PSA 75.72, QED 0.5
Compound (SMILES): COc1ccc(CNc2ccc(Cc3c[nH]c4ncc(C)cc34)c(F)n2)cn1
InChIKey: RTGVPSAXYOKKJK-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 377.42, ALogP 4.01, HBA 5, HBD 2, PSA 75.72, QED 0.5
Compound (SMILES): COc1cnc2[nH]cc(Cc3ccc(NCc4ccc(OC)nc4)nc3F)c2c1
InChIKey: FBZGWPOPVWFXLR-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Biochemical Assay: In one assay the biochemical activity IC50 values are determined with respect to inhibition of Fms kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested, dissolved in DMSO (1 uL), are added to a white 384-well plate (Costar #3705). Working stocks of Fms kinase (Invitrogen #PV3249), biotin-(E4Y)10 substrate (Upstate Biotech, Cat#12-440), and ATP (Sigma, Cat#A-3377) are prepared in 25 mM Hepes pH 7.5, 0.5 mM MgCl2, 2 mM MnCl2, 2 mM DTT, 0.01% BSA, and 0.01% Tween-20. All components are added to the 384-well plate for a final concentration of 1 ng/well Fms, 30 nM biotin-(E4Y)10 (Upstate Biotechnology) and 100 uM ATP in a volume of 20 uL. Each sample is at 5% DMSO. The plate is then incubated for 20 minutes at 30 C. Just before use, working stocks of donor and acceptor beads from the AlphaScreen PY20 Detection Kit (PerkinElmer, Cat#676601M) are prepared in 25 mM Hepes pH 7.5.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 393.42, ALogP 3.71, HBA 6, HBD 2, PSA 84.95, QED 0.47
Compound (SMILES): COc1ccc(CNc2ccc(Cc3c[nH]c4ncc(F)cc34)c(F)n2)cn1
InChIKey: WFKFRFWYVHBMNZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 381.39, ALogP 3.84, HBA 5, HBD 2, PSA 75.72, QED 0.5
Compound (SMILES): Cc1cnc2[nH]cc(Cc3ccc(NCc4ccc(C(F)(F)F)nc4)nc3)c2c1
InChIKey: DXDZIZAESKHCEH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 397.4, ALogP 4.88, HBA 4, HBD 2, PSA 66.49, QED 0.5
Compound (SMILES): COc1ncc(F)cc1CNc1ccc(Cc2c[nH]c3ncc(NC(C)=O)cc23)c(F)n1
InChIKey: IWGLCABRVPLEJZ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.44, ALogP 3.8, HBA 6, HBD 3, PSA 104.82, QED 0.38
Compound (SMILES): CS(=O)(=O)Nc1cnc2[nH]cc(Cc3ccc(NCc4ccc(Cl)nc4)nc3F)c2c1
InChIKey: KIYZZSWMJCJKKW-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 460.92, ALogP 3.72, HBA 6, HBD 3, PSA 112.66, QED 0.36
Compound (SMILES): COc1ccc(CNc2ncc(Cc3c[nH]c4ncc(C)cc34)cc2F)cn1
InChIKey: IDCXHTGCSOGOJL-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Biochemical Assay: In one assay the biochemical activity IC50 values are determined with respect to inhibition of c-Kit kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested are dissolved in DMSO to a concentration of 20 mM. These are diluted 30 uL into 120 uL of DMSO (4 mM) and 1 uL is added to an assay plate. These are then serially diluted 1:2 (50 uL to 100 uL DMSO) for a total of 8 points. Plates are prepared such that each kinase reaction is 20 uL in 1x kinase buffer (25 mM HEPES, pH 7.5, 2 mM MgCl2, 2 mM MnCl2, 0.01% Tween-20, 1 mM DTT, 0.01% BSA), 5% DMSO and 100 uM ATP. Substrate is 30 nM biotin-(E4Y)10 (Millipore). C-kit kinase (obtained from Millipore (#14-559) or is prepared as described in U.S. Patent Application Publication Number 2009/0076046, the disclosure of which is hereby incorporated by reference as it relates to this assay) is at 0.75 ng per sample.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 377.42, ALogP 4.01, HBA 5, HBD 2, PSA 75.72, QED 0.53
Compound (SMILES): COc1ccnc2[nH]cc(Cc3ccc(NCc4ccc(Cl)cc4)nc3F)c12
InChIKey: OLQODSJHRJYJIW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition Enzyme Assay: CYP (Cytochrome P450) enzymes are the major drug metabolizing enzymes present in the liver. The inhibition of CYP enzyme activity (IC50) for each of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4(BFC) and CYP3A4(BQ) is determined for compounds, where inhibition of metabolism of a known substrate leads to a decrease in the fluorescence of the metabolized product. The fluorescence of the product is monitored as a function of compound concentration.Compounds are dissolved in DMSO to a concentration of 100 mM. These are diluted 1 uL into 82 uL of acetonitrile. An 11 uL aliquot of this solution is then added to 204 uL of cofactor mix (1.3% NADPH Regeneration system Solution A, 1.04% NADPH Regeneration system Solution B from BD Biosciences, 5% acetonitrile and 0.05% DMSO). These are then serially diluted 1:1 (160 uL to 160 uL co-factor mix) for a total of 10 points. A 10 uL aliquot of this final mixture is dispensed into 384 well assay plates.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 396.85, ALogP 4.96, HBA 4, HBD 2, PSA 62.83, QED 0.45