lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1nccc1-c1cc(C(F)(F)F)ccc1-c1cccc2c1CCN(S(=O)(=O)Nc1ncccn1)C2
InChIKey: LKAXTXRXNLOAHP-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 7260 nM (pChEMBL 5.139999866485596)
Descriptors: MW 514.53, ALogP 4.28, HBA 6, HBD 1, PSA 93.01, QED 0.43
Compound (SMILES): COc1ncccc1-c1cccc2c1CCN(S(=O)(=O)Nc1ncns1)C2
InChIKey: GEZQWAHRDCWJML-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 14600 nM (pChEMBL 4.840000152587891)
Descriptors: MW 403.49, ALogP 2.32, HBA 7, HBD 1, PSA 97.31, QED 0.7
Compound (SMILES): CC(C)(C)OC(=O)N1CC=C(c2cccc3c2CCN(S(=O)(=O)Nc2ncns2)C3)CC1
InChIKey: ARXYLVKKDMSLPD-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.61, ALogP 3.28, HBA 7, HBD 1, PSA 104.73, QED 0.72
Compound (SMILES): COc1cc(C(F)(F)F)ccc1-c1ncnc2c1CCN(S(=O)(=O)Nc1ncc(F)s1)C2
InChIKey: XEOCNZBBZFBCME-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.48, ALogP 3.48, HBA 7, HBD 1, PSA 97.31, QED 0.55
Compound (SMILES): COc1cc(-c2ccc(F)c(F)c2)ccc1-c1cccc2c1CCN(S(=O)(=O)Nc1nncs1)C2
InChIKey: DRFLHOUHDJPQKF-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 514.58, ALogP 4.87, HBA 6, HBD 1, PSA 84.42, QED 0.4
Compound (SMILES): Cn1nccc1-c1cc(C(F)(F)F)ccc1-c1cccc2c1CCN(S(=O)(=O)Nc1nccs1)C2
InChIKey: NORLXSKHKCEGDU-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 519.57, ALogP 4.94, HBA 6, HBD 1, PSA 80.12, QED 0.4
Compound (SMILES): CC(C)(C)OC(=O)N1CC=C(c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncns2)C3)CC1
InChIKey: SDNRGNTWXJZKMN-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 5630 nM (pChEMBL 5.25)
Descriptors: MW 621.71, ALogP 5.96, HBA 7, HBD 1, PSA 104.73, QED 0.38
Compound (SMILES): COc1cc(C(F)(F)F)ccc1-c1ncnc2c1CCN(S(=O)(=O)Nc1nccs1)C2
InChIKey: SSHUJNUARSWDGM-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 16500 nM (pChEMBL 4.78000020980835)
Descriptors: MW 471.49, ALogP 3.34, HBA 7, HBD 1, PSA 97.31, QED 0.61
Compound (SMILES): O=S(=O)(Nc1ncc(F)s1)N1CCc2c(cccc2-c2ccc(C(F)(F)F)cc2C2=CCNCC2)C1
InChIKey: JDTSMWBMEDXGCW-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 25.8 nM (pChEMBL 7.590000152587891)
Descriptors: MW 538.59, ALogP 5.06, HBA 5, HBD 2, PSA 74.33, QED 0.45
Compound (SMILES): CN1CC=C(c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: JIHSVBWAKKLMNO-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 91.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 552.62, ALogP 5.4, HBA 5, HBD 1, PSA 65.54, QED 0.43
Compound (SMILES): CN1CC=C(c2ccc(C(F)(F)F)cc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: GPFJATGTAHFICK-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 552.62, ALogP 5.4, HBA 5, HBD 1, PSA 65.54, QED 0.43
Compound (SMILES): CN1CCN(c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)CC1
InChIKey: JMHSSFSYBUYYML-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 555.62, ALogP 4.43, HBA 6, HBD 1, PSA 68.78, QED 0.47
Compound (SMILES): Cc1cn(-c2cc(C(F)(F)F)ccc2-c2cccc3c2CCN(S(=O)(=O)Nc2ncc(F)s2)C3)cn1
InChIKey: MVOYXQLNULAYDH-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 = 395 nM (pChEMBL 6.400000095367432)
Descriptors: MW 537.56, ALogP 5.18, HBA 6, HBD 1, PSA 80.12, QED 0.36
Compound (SMILES): Cc1cncn1-c1cc(C(F)(F)F)ccc1-c1cccc2c1CCN(S(=O)(=O)Nc1ncc(F)s1)C2
InChIKey: KCAFDAXZAOOGJL-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Ion Works Quattro (IWQ) Assay: In Vitro Assays 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the Ion Works® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, CA). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 537.56, ALogP 5.18, HBA 6, HBD 1, PSA 80.12, QED 0.36
Compound (SMILES): O=S(=O)(Nc1ncns1)N1CCc2c(cccc2-c2c(Br)cc(C(F)(F)F)cc2C2=CCNCC2)C1
InChIKey: BPHPTRAVFDEGTB-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: PatchExpress (PX) Assay: 293 cells stably transfected with human Navl .7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, CA). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes. Peak sodium current was measured at the end of the compound addition period to determine percent inhibition.
Measurement: IC50 = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 600.49, ALogP 5.08, HBA 6, HBD 2, PSA 87.22, QED 0.43
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 3.64 nM (pChEMBL 8.4399995803833)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp method
Measurement: IC50 = 67000 nM (pChEMBL 4.170000076293945)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): O=C(c1nn(-c2ccc(CN3CCOCC3)cc2)c2c1CS(=O)(=O)c1c(F)cccc1-2)N1CCOCC1
InChIKey: NFHSJYKXENYICE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using phosphatidyl inositol as substrate by scintillation proximity assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 526.59, ALogP 2.27, HBA 8, HBD 0, PSA 93.97, QED 0.51
Compound (SMILES): NC(=O)n1cc(NC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc21
InChIKey: NRMJBMPLENRGCS-LYRGGWFBSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of complement factor D in human whole blood assessed as decrease in zymosan-induced AP activation mediated soluble MAC complex formation preincubated for 15 mins followed by zymosan addition measured after 40 mins by ELISA
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 483.33, ALogP 3.36, HBA 5, HBD 3, PSA 122.35, QED 0.49
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of dofetilide binding to human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C(F)F)N=C(N)O[C@@H]4C[C@@H]43)c2)cn1
InChIKey: QWKKSXTZIMZFAW-NOPHNCEQSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Fluorescence Resonance Energy Transfer Assay: Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm).
Measurement: IC50 = 42450 nM (pChEMBL 4.369999885559082)
Descriptors: MW 449.36, ALogP 2.21, HBA 7, HBD 2, PSA 111.72, QED 0.52
Compound (SMILES): Cc1nc(OCC(F)(F)F)cnc1C(=O)Nc1cc(F)c(Cl)c([C@]2(CF)N=C(N)O[C@H]3C[C@H]32)c1
InChIKey: UZKQOQQRJKLGGG-KPGGICDASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer Assay: The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm).
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 505.83, ALogP 3.67, HBA 7, HBD 2, PSA 111.72, QED 0.58
Compound (SMILES): O=C(CCCOc1ccccc1)C(F)(F)F
InChIKey: YHXZJYMEFQXYQI-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: Ki = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 232.2, ALogP 2.98, HBA 2, HBD 0, PSA 26.3, QED 0.73
Compound (SMILES): O=C(CCCCOc1ccccc1)C(F)(F)F
InChIKey: UGRZUZDBQSORDW-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: Ki = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 246.23, ALogP 3.37, HBA 2, HBD 0, PSA 26.3, QED 0.72
Compound (SMILES): NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)c1cccc(-c2ccc(Oc3ccc(F)cc3)cc2)n1
InChIKey: AUFYEEJEQHHJNN-VWLOTQADSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: In Vitro Assay : The assay buffer was formulated by removing 120 mL from a 1 L bottle of fresh, sterile dH2O (Mediatech, Herndon, Va.) and adding 100 mL of 10×HBSS that does not contain Ca++ or Mg++ (Gibco, Invitrogen, Grand Island, N.Y.) followed by 20 mL of 1.0 M Hepes, pH 7.3 (Fisher Scientific, BP299-100). The final buffer consisted of 20 mM Hepes, pH 7.3, 1.261 mM CaCl2, 0.493 mM MgCl2, 0.407 mM Mg(SO)4, 5.33 mM KCl, 0.441 mM KH2PO4, 137 mM NaCl, 0.336 mM Na2HPO4 and 0.556 mM D-glucose (Hanks et al., Proc. Soc. Exp. Biol. Med. 71:196 (1949)), and the simple formulation was typically the basic buffer throughout the assay (i.e., all wash and addition steps).
Measurement: IC50 = 2890 nM (pChEMBL 5.539999961853027)
Descriptors: MW 471.49, ALogP 4.21, HBA 5, HBD 3, PSA 114.54, QED 0.36
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(C)C)C(=O)N1c1ccc(-c2ccsc2)cc1
InChIKey: IJIRNLYMFCQLQL-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 443.57, ALogP 6.19, HBA 4, HBD 1, PSA 58.22, QED 0.41
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(C)C)C(=O)N1c1ccc(-c2ncco2)cc1
InChIKey: LWHAQVIKMODEMM-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 428.49, ALogP 5.12, HBA 5, HBD 1, PSA 84.25, QED 0.49
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(CO)CO)C(=O)N1c1ccc(-c2ccon2)cc1
InChIKey: JUOGKKFFOPMFTH-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 460.49, ALogP 3.07, HBA 7, HBD 3, PSA 124.71, QED 0.39
Compound (SMILES): NC1=N[C@@H](c2ccc(Cl)cc2)CO1
InChIKey: JOFNIUCTGCVSGU-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q923Y8
Assay: Radioligand Binding Assay: Radioligand binding assay using TAAR1.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 196.64, ALogP 1.73, HBA 3, HBD 1, PSA 47.61, QED 0.74
Compound (SMILES): C[C@]1(c2ccccc2Cl)COC(N)=N1
InChIKey: DHXYGMYUXSOEGU-SNVBAGLBSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 210.66, ALogP 1.9, HBA 3, HBD 1, PSA 47.61, QED 0.77
Compound (SMILES): NC1=N[C@@H](c2cccc(Cl)c2)CO1
InChIKey: CYOQNBYJYMBMTG-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 246 nM (pChEMBL 6.610000133514404)
Descriptors: MW 196.64, ALogP 1.73, HBA 3, HBD 1, PSA 47.61, QED 0.74
Compound (SMILES): NC1=N[C@@H](c2cccc(F)c2)CO1
InChIKey: JKVQLTDZPQITFF-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 180.18, ALogP 1.21, HBA 3, HBD 1, PSA 47.61, QED 0.71
Compound (SMILES): C[C@]1(c2ccc(Br)cc2)COC(N)=N1
InChIKey: PFGQJLSABMTQRX-SNVBAGLBSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q923Y8
Assay: Radioligand Binding Assay: Radioligand binding assay using TAAR1.
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 255.12, ALogP 2.01, HBA 3, HBD 1, PSA 47.61, QED 0.83
Compound (SMILES): CC[C@@H](C[C@H]1COC(N)=N1)c1ccccc1
InChIKey: IXDKFUBXESWHSL-JQWIXIFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 218.3, ALogP 2.28, HBA 3, HBD 1, PSA 47.61, QED 0.84
Compound (SMILES): CCc1cc(Cl)ccc1[C@H]1COC(N)=N1
InChIKey: QMJCJXYDQQSDCX-SNVBAGLBSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 224.69, ALogP 2.29, HBA 3, HBD 1, PSA 47.61, QED 0.84
Compound (SMILES): NC1=N[C@@H](c2ccc(Cl)cc2C2CC2)CO1
InChIKey: OHEHXHSMXPWYQM-LLVKDONJSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 236.7, ALogP 2.6, HBA 3, HBD 1, PSA 47.61, QED 0.86
Compound (SMILES): O[C@H]1[C@H](O)CNC[C@@H]1C(F)F
InChIKey: QSMPJEGWIQSKCL-VPENINKCSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 167.16, ALogP -0.81, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): O[C@@H]1[C@@H](Cc2ccccc2)CNC[C@H]1O
InChIKey: WUEAMJOBFYKMLP-QJPTWQEYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 207.27, ALogP 0.17, HBA 3, HBD 3, PSA 52.49, QED 0.65
Compound (SMILES): O[C@@H]1[C@@H]([C@H](O)c2ccccc2)CNC[C@H]1O
InChIKey: AQILKYRWFPWHAA-DDHJBXDOSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 223.27, ALogP -0.34, HBA 4, HBD 4, PSA 72.72, QED 0.55
Compound (SMILES): CC(C)(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: PVGDVTWSNAIFDH-RRKCRQDMSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 175.23, ALogP -1.3, HBA 4, HBD 4, PSA 72.72, QED 0.4
Compound (SMILES): CC[C@@H](F)C1CNC[C@@H](O)[C@@H]1O
InChIKey: JJOAXUOFRVBCHL-UIYHXYAWSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 177.22, ALogP -0.32, HBA 3, HBD 3, PSA 52.49, QED 0.54
Compound (SMILES): C[C@H]1CC[C@H](n2c3cnccc3c3cnc(Nc4cc5c(cn4)CCNC5)nc32)CC1
InChIKey: PADUNTTWTYUKQZ-RZDIXWSQSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 257 nM (pChEMBL 6.590000152587891)
Descriptors: MW 413.53, ALogP 4.52, HBA 7, HBD 2, PSA 80.55, QED 0.51
Compound (SMILES): CC1CNCc2ccc(Nc3ncc4c5ccncc5n([C@H]5CC[C@H](C)CC5)c4n3)nc21
InChIKey: CMWZJGXVESUMJY-FKIWDRNQSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 31.3 nM (pChEMBL 7.5)
Descriptors: MW 427.56, ALogP 5.08, HBA 7, HBD 2, PSA 80.55, QED 0.47
Compound (SMILES): CC(=O)N1Cc2ccc(Nc3ncc4c5ccncc5n([C@H]5CC[C@H](C)CC5)c4n3)nc2C(C)C1
InChIKey: YQUHLIQEGXFNCX-ZLNWJBBSSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 469.59, ALogP 5.33, HBA 7, HBD 1, PSA 88.83, QED 0.44
Compound (SMILES): COc1cc2c3cnc(Nc4ccc5c(n4)CCNC5)nc3n([C@H]3CC[C@H](C)CC3)c2cn1
InChIKey: BSWDAWSAVMWHIA-JCNLHEQBSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 1790 nM (pChEMBL 5.75)
Descriptors: MW 443.56, ALogP 4.52, HBA 8, HBD 2, PSA 89.78, QED 0.48
Compound (SMILES): CC(=O)N1Cc2ccc(Nc3ncc4c5ccncc5n([C@H]5CC[C@H](C)CC5)c4n3)nc2[C@@H](C)C1
InChIKey: YQUHLIQEGXFNCX-ZWOKBUDYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 463 nM (pChEMBL 6.329999923706055)
Descriptors: MW 469.59, ALogP 5.33, HBA 7, HBD 1, PSA 88.83, QED 0.44
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-YTJLLHSVSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-BSOCMFCZSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase PLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYY3
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 813 nM (pChEMBL 6.090000152587891)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Solute carrier family 22 member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSA0
Assay: Inhibition of OAT4 (unknown origin)
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): O=C(c1nn(-c2ccc(CN3CCOCC3)cc2)c2c1CS(=O)(=O)c1c(F)cccc1-2)N1CCOCC1
InChIKey: NFHSJYKXENYICE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using phosphatidyl inositol as substrate by scintillation proximity assay
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 526.59, ALogP 2.27, HBA 8, HBD 0, PSA 93.97, QED 0.51
Compound (SMILES): NC(=O)n1cc(NC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc21
InChIKey: NRMJBMPLENRGCS-LYRGGWFBSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using diclofenac as substrate
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 483.33, ALogP 3.36, HBA 5, HBD 3, PSA 122.35, QED 0.49
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): O=C(CCCOc1ccccc1)C(F)(F)F
InChIKey: YHXZJYMEFQXYQI-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: IC50 = 69400 nM (pChEMBL 4.159999847412109)
Descriptors: MW 232.2, ALogP 2.98, HBA 2, HBD 0, PSA 26.3, QED 0.73
Compound (SMILES): O=C(CCCCOc1ccccc1)C(F)(F)F
InChIKey: UGRZUZDBQSORDW-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Enzyme Assay: All compound solutions are made to a concentration of 10 mM in DMSO. To test the stability of the compounds in enzyme assay conditions, 25 nmoles of the compound are incubated in TME buffer with 0.1% BSA (final volume of 250 uL) for 15 minutes at 37 C. Samples (100 uL) are taken at the start of the assay and after 15 minutes, diluted 1:5 with acetonitrile and centrifuged (20,000 RCF, five minutes, room temperature) to precipitate the proteins. The resulting supernatant is injected onto the HPLC. Calculations for determining the percent compound remaining are described in the following equation:% R=Peak Area (T15)/Peak Area (T0)To determine whether or not the compounds are good substrates for FAAH, 25 nmoles of the compound were incubated with 75 ug enzyme preparation in TME buffer with 0.1% BSA (final volume 250 uL). The reaction mixture is treated in the same manner as described above.
Measurement: IC50 = 18800 nM (pChEMBL 4.730000019073486)
Descriptors: MW 246.23, ALogP 3.37, HBA 2, HBD 0, PSA 26.3, QED 0.72
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(C)C)C(=O)N1c1ccc(-c2ccsc2)cc1
InChIKey: IJIRNLYMFCQLQL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 443.57, ALogP 6.19, HBA 4, HBD 1, PSA 58.22, QED 0.41
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(C)C)C(=O)N1c1ccc(-c2ncco2)cc1
InChIKey: LWHAQVIKMODEMM-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Inhibiton Assay: Inhibition assay using human P2X3 receptor gene (GeneBank accession number Y07683).
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 428.49, ALogP 5.12, HBA 5, HBD 1, PSA 84.25, QED 0.49
Compound (SMILES): COc1ccccc1C1c2c(n[nH]c2C(C)(CO)CO)C(=O)N1c1ccc(-c2ccon2)cc1
InChIKey: JUOGKKFFOPMFTH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 460.49, ALogP 3.07, HBA 7, HBD 3, PSA 124.71, QED 0.39
Compound (SMILES): CC[C@@H](C[C@H]1COC(N)=N1)c1ccccc1
InChIKey: IXDKFUBXESWHSL-JQWIXIFHSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 218.3, ALogP 2.28, HBA 3, HBD 1, PSA 47.61, QED 0.84
Compound (SMILES): O[C@H]1[C@H](O)CNC[C@@H]1C(F)F
InChIKey: QSMPJEGWIQSKCL-VPENINKCSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 25.9 nM (pChEMBL 7.590000152587891)
Descriptors: MW 167.16, ALogP -0.81, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): O[C@@H]1[C@@H](Cc2ccccc2)CNC[C@H]1O
InChIKey: WUEAMJOBFYKMLP-QJPTWQEYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 207.27, ALogP 0.17, HBA 3, HBD 3, PSA 52.49, QED 0.65