lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCc1c(C)nn2c(=O)cc(-c3ccc(OC)cc3)[nH]c12
InChIKey: BYSWJWQTNFTSNG-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Biochemical Assay for CK2 Activity: Purified CK2a2 (NP_001887; human full-length protein, GST tagged) from insect cells (final concentration 1.2 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM Hepes (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and CK2 sub [RRRDDDSDDD] (20 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 297.36, ALogP 2.96, HBA 4, HBD 1, PSA 59.39, QED 0.81
Compound (SMILES): CCOC(=O)Cc1cc(=O)n2nc(-c3ccccc3)c(-c3ccccc3)c2[nH]1
InChIKey: OISGGHMAUKHGMH-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Aldehyde Dehydrogenase 1 (ALDH1A1). (Class of assay: confirmatory) [Related pubchem assays: 1030 (qHTS Validation Assay for Inhibitors of aldehyde dehydrogenase 1 (ALDH1A1))]
Measurement: Potency = 25118.9 nM (pChEMBL 4.599999904632568)
Descriptors: MW 373.41, ALogP 3.46, HBA 5, HBD 1, PSA 76.46, QED 0.54
Compound (SMILES): COc1ccc(Cc2nn3c(=O)cc(C)[nH]c3c2-c2ccccc2)cc1
InChIKey: VHVXLXRQYLPCIY-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: Kinase Luminescence Assay: Table 1: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 μg) is added to a 50 μL reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 μg of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 μL of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 μL of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.4, ALogP 3.6, HBA 4, HBD 1, PSA 59.39, QED 0.61
Compound (SMILES): Cc1cc(=O)n2nc(C)c(-c3ccc(Cl)cc3)c2[nH]1
InChIKey: UYPCVFBHDSUYSS-UHFFFAOYSA-N
Target: Prelamin-A/C (SINGLE PROTEIN), Homo sapiens
UniProt: P02545
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Modulators of Lamin A Splicing. (Class of assay: confirmatory) 
Measurement: Potency = 25118.9 nM (pChEMBL 4.599999904632568)
Descriptors: MW 273.72, ALogP 2.96, HBA 3, HBD 1, PSA 50.16, QED 0.74
Compound (SMILES): Cc1nn2c(=O)c3c([nH]c2c1-c1ccc(Cl)cc1)CCC3
InChIKey: UCNZBUKKRNGBSJ-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase). (Class of assay: confirmatory) [Related pubchem assays: 2429 (Confirmation qHTS Assay for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase)), 2407 (Probe Development Summary for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase)), 2427 (Thermal Shift Assay for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase))]
Measurement: Potency = 28183.8 nM (pChEMBL 4.550000190734863)
Descriptors: MW 299.76, ALogP 3.14, HBA 3, HBD 1, PSA 50.16, QED 0.75
Compound (SMILES): CCCc1cc(=O)n2nc(C)c(-c3ccc(Cl)cc3)c2[nH]1
InChIKey: PPACHXJPCSORHE-UHFFFAOYSA-N
Target: Streptokinase A (SINGLE PROTEIN), Streptococcus pyogenes serotype M1
UniProt: P10520
Assay: PUBCHEM_BIOASSAY: Luminescence Microorganism-Based Dose Confirmation HTS to Identify Inhibitors of Streptokinase Promotor Activity. (Class of assay: confirmatory) [Related pubchem assays: 1677 (Project Summary), 1662 (Primary HTS)]
Measurement: EC50 = 5807 nM (pChEMBL 5.239999771118164)
Descriptors: MW 301.78, ALogP 3.6, HBA 3, HBD 1, PSA 50.16, QED 0.8
Compound (SMILES): O=c1cc(-c2ccc([N+](=O)[O-])cc2)[nH]c2c(-c3ccc(Cl)cc3)c(Cc3ccccc3)nn12
InChIKey: GUUWHOSUKOCRHG-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: Kinase Luminescence Assay: Table 1: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 μg) is added to a 50 μL reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 μg of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 μL of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 μL of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 456.89, ALogP 5.51, HBA 5, HBD 1, PSA 93.3, QED 0.28
Compound (SMILES): C[C@H]1CCc2cc(-c3nc(Cl)nc4[nH]ccc34)ccc2N1C(=O)c1ccc(O)cc1O
InChIKey: QTZREWXFIMJBHN-LBPRGKRZSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDHK1 in human PC3 cells assessed as decrease in phosphorylation of E1alpha subunit at serine 293 residue after 1 hr by ELISA
Measurement: IC50 = 1820 nM (pChEMBL 5.739999771118164)
Descriptors: MW 434.88, ALogP 4.67, HBA 5, HBD 3, PSA 102.34, QED 0.4
Compound (SMILES): Cc1cc2ccccc2nc1-c1ccc2c(c1)CC[C@H](C)N2C(=O)c1ccc(O)cc1O
InChIKey: ZPNZQVNPYMEKML-KRWDZBQOSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Binding affinity to PDHK1 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 424.5, ALogP 5.6, HBA 4, HBD 2, PSA 73.66, QED 0.44
Compound (SMILES): C[C@H]1CCc2cc(-c3nc(Cl)nc4ccsc34)ccc2N1C(=O)c1ccc(O)cc1O
InChIKey: ZWUZKCPHVDLAAI-LBPRGKRZSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDHK1 in human PC3 cells assessed as decrease in phosphorylation of E1alpha subunit at serine 293 residue after 1 hr by ELISA
Measurement: IC50 = 2780 nM (pChEMBL 5.559999942779541)
Descriptors: MW 451.94, ALogP 5.4, HBA 6, HBD 2, PSA 86.55, QED 0.4
Compound (SMILES): COc1cc(OCc2csc(-c3ccc(S(C)(=O)=O)cc3)n2)c2cc(-c3cn4nc(OC)sc4n3)oc2c1
InChIKey: AUHROPMDFWDFRD-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Platelet Aggregation (PRP) Assay : The ability of the compounds of the current invention to inhibit platelet aggregation induced by gamma-thrombin was tested in a 96-well microplate aggregation assay format. Briefly, PRP or washed platelet suspension (100 μl) was pre-incubated for 5 minutes at room temperature with varying concentrations of compounds. Aggregation was initiated by ¿10-50 nM gamma thrombin (Haematologic Technologies, Essex Junction, Vt.), which was titrated daily to achieve 80% platelet aggregation. Refludan at 1 U/mL (Berlex, Montville, N.J.) was added to the gamma thrombin sample to prevent PAR1 activation induced by residual alpha-thrombin contamination. The plate was then placed into a 37° C. Molecular Devices (Sunnyvale, Calif.) SPECTRAMAX Plus Plate Reader. The plate was mixed for 10 seconds before the first read and 50 seconds between each read for up to 15 minutes at 405 nM. Data was collected with SOFTMAX 4.71 software. The plate also included an untreated control sample which served as ODmax, while buffer containing no platelets was the ODmin. Platelet aggregation was determined by subtracting the ODmax from the ODmin for the 100% aggregation value. In experimental samples, the observed transmission was subtracted from the minimum value and then compared to the 100% aggregation value to determine the percentage aggregation. IC50 values are determined using Excel Fit software. The aggregation assays were also employed to test the selectivity of the compound against other platelet receptors by using SFFLRR for PAR1, collagen (Chrono-Log, Havertown, Pa.) for collagen receptors, ADP for P2Y1 and P2Y12 and U46619 (Cayman Chemical, Ann Arbor, Mich.) for thromboxane receptors.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 568.66, ALogP 5.33, HBA 12, HBD 0, PSA 118.05, QED 0.24
Compound (SMILES): COc1cc(OCc2nc(N3CCOCC3)sc2C)c2cc(-c3cn4nc(OC)sc4n3)oc2c1
InChIKey: MINMDCMSHDBHKG-UHFFFAOYSA-N
Target: Proteinase-activated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25116
Assay: Antagonist activity at human PAR1 expressed in Ga15-HEK293 cells assessed as reduction in PAR1 AP SFFLRR-NH2-induced cytosolic calcium incubated for 24 hrs by FLIPR - calcium mobilization assay
Measurement: IC50 > 3162 nM (pChEMBL 5.5)
Descriptors: MW 513.6, ALogP 4.4, HBA 12, HBD 0, PSA 96.38, QED 0.31
Compound (SMILES): Cc1cc(=O)n2nc(-c3ccc(Cl)cc3)cc2[nH]1
InChIKey: OHQFWCMJFWAHQO-UHFFFAOYSA-N
Target: NPC intracellular cholesterol transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O15118
Assay: PUBCHEM_BIOASSAY: qHTS Assay for NPC1 Promoter Activators. (Class of assay: confirmatory) 
Measurement: Potency = 3981.1 nM (pChEMBL 5.400000095367432)
Descriptors: MW 259.7, ALogP 2.65, HBA 3, HBD 1, PSA 50.16, QED 0.73
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCOCC3)nc2c1
InChIKey: RVIHPCCTLCBNIH-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 335.36, ALogP 2.83, HBA 5, HBD 1, PSA 75.55, QED 0.79
Compound (SMILES): CN1CCCN(c2nc3cc(C(=O)O)ccc3nc2-c2ccccc2)CC1
InChIKey: WQLHETUGEZSAQT-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 362.43, ALogP 3.14, HBA 5, HBD 1, PSA 69.56, QED 0.77
Compound (SMILES): CC(C)Nc1nc2cc(C(=O)O)ccc2nc1-c1ccccc1
InChIKey: TWTQQTMBJLBKKS-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 307.35, ALogP 3.82, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ncccn4)CC3)nc2c1
InChIKey: ALUNRJJRXDRTNS-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 412.45, ALogP 3.11, HBA 7, HBD 1, PSA 95.34, QED 0.55
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ccc(C(F)(F)F)cn4)CC3)nc2c1
InChIKey: ZPXWVIFNUUUDPR-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 479.46, ALogP 4.74, HBA 6, HBD 1, PSA 82.45, QED 0.45
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ccc5ccccc5n4)CC3)nc2c1
InChIKey: SGEDGUNHRNELJK-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 461.53, ALogP 4.87, HBA 6, HBD 1, PSA 82.45, QED 0.41
Compound (SMILES): O=C(O)c1ccc2nc(N3CCC(c4ccc(Cl)cc4)CC3)c(-c3ccc(F)cc3)nc2c1
InChIKey: UKFDKTCZAAYLSR-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 461.92, ALogP 6.17, HBA 4, HBD 1, PSA 66.32, QED 0.39
Compound (SMILES): COc1ccc(C2CCN(c3nc4ccc(C(=O)O)cc4nc3-c3ccc(F)cc3)CC2)cc1
InChIKey: DKHGDKUUKKIFFR-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 457.51, ALogP 5.53, HBA 5, HBD 1, PSA 75.55, QED 0.42
Compound (SMILES): O=C(O)c1ccc2nc(N3CCC(c4ccc(C(F)(F)F)cc4)CC3)c(-c3ccc(F)cc3)nc2c1
InChIKey: XNQAOBKHXBGGHD-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 495.48, ALogP 6.54, HBA 4, HBD 1, PSA 66.32, QED 0.33
Compound (SMILES): COc1cc(OCc2csc(-c3ccc(C(=O)N(C)C)cc3)n2)c2cc(-c3cn4nc(OC)sc4n3)oc2c1
InChIKey: KEEBLYWBELVGPQ-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes
Measurement: IC50 > 7000 nM (pChEMBL 5.15500020980835)
Descriptors: MW 561.65, ALogP 5.63, HBA 11, HBD 0, PSA 104.22, QED 0.24
Compound (SMILES): COc1cc(OCc2csc(N3CCCOCC3)n2)c2cc(-c3cn4nc(OC)sc4n3)oc2c1
InChIKey: OLFJSYFEVMJTBF-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Platelet Aggregation (PRP) Assay : The ability of the compounds of the current invention to inhibit platelet aggregation induced by gamma-thrombin was tested in a 96-well microplate aggregation assay format. Briefly, PRP or washed platelet suspension (100 μl) was pre-incubated for 5 minutes at room temperature with varying concentrations of compounds. Aggregation was initiated by ¿10-50 nM gamma thrombin (Haematologic Technologies, Essex Junction, Vt.), which was titrated daily to achieve 80% platelet aggregation. Refludan at 1 U/mL (Berlex, Montville, N.J.) was added to the gamma thrombin sample to prevent PAR1 activation induced by residual alpha-thrombin contamination. The plate was then placed into a 37° C. Molecular Devices (Sunnyvale, Calif.) SPECTRAMAX Plus Plate Reader. The plate was mixed for 10 seconds before the first read and 50 seconds between each read for up to 15 minutes at 405 nM. Data was collected with SOFTMAX 4.71 software. The plate also included an untreated control sample which served as ODmax, while buffer containing no platelets was the ODmin. Platelet aggregation was determined by subtracting the ODmax from the ODmin for the 100% aggregation value. In experimental samples, the observed transmission was subtracted from the minimum value and then compared to the 100% aggregation value to determine the percentage aggregation. IC50 values are determined using Excel Fit software. The aggregation assays were also employed to test the selectivity of the compound against other platelet receptors by using SFFLRR for PAR1, collagen (Chrono-Log, Havertown, Pa.) for collagen receptors, ADP for P2Y1 and P2Y12 and U46619 (Cayman Chemical, Ann Arbor, Mich.) for thromboxane receptors.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 513.6, ALogP 4.48, HBA 12, HBD 0, PSA 96.38, QED 0.31
Compound (SMILES): COc1ccc(-c2nc3ccc(-c4nnn[nH]4)cc3nc2-c2ccc(OC)cc2)cc1
InChIKey: JXWYOCARONMUEH-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PAS Kinase Luminescence Assay: One assay for purified hPASK activity utilizes the Kinase-Glo Luminescent Kinase Assay (Promega), which quantifies the amount of ATP remaining in solution following kinase reaction. The assay is carried out in a 96-well plate format and is performed by adding a volume of Kinase-Glo Reagent (Promega, catalog #V3771) equal to the volume of solution in the well of a completed kinase reaction. Kinase-Glo reagent contains Luciferase and its substrate. After addition to a kinase reaction it allows to measure luminescence. The amount of ATP left in solution at the time of Kinase-Glo Plus addition is directly proportional to the luminescence that is measured in each well, and inversely correlated with kinase activity.Purified hPASK from insect cells (0.02 g) is added to a 50 L reaction mix containing 40 mM HEPES (pH 7.0), 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 1 g of MBP protein. Inhibitory compounds are then added and the mixture is incubated for 10 min at 25° C. before adding 5 L of ATP (at desired concentration). The reaction is allowed to proceed at 25° C. for 1 hour before adding 50 L of Kinase-Glo reagent. The luminescence is measured as soon as 10 minutes after Kinase-Glo reagent is added.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 410.44, ALogP 4.16, HBA 7, HBD 1, PSA 98.7, QED 0.46
Compound (SMILES): CN(C1CCN(c2nc3cc(C(=O)O)ccc3nc2-c2ccccc2)CC1)S(C)(=O)=O
InChIKey: ZDHMRLLHWVUSBY-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 440.53, ALogP 2.86, HBA 6, HBD 1, PSA 103.7, QED 0.65
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCCc4ccccc43)nc2c1
InChIKey: QNTAFDGTGJMGAA-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 381.44, ALogP 5.08, HBA 4, HBD 1, PSA 66.32, QED 0.54
Compound (SMILES): CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccccc1
InChIKey: KAHWLDVDHKQLSX-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 321.38, ALogP 3.84, HBA 4, HBD 1, PSA 66.32, QED 0.79
Compound (SMILES): CN(c1nc2cc(C(=O)O)ccc2nc1-c1ccccc1)C1CC1
InChIKey: IITMEKDTKBWXSY-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 319.36, ALogP 3.59, HBA 4, HBD 1, PSA 66.32, QED 0.8
Compound (SMILES): COC[C@H]1CCCN1c1nc2cc(C(=O)O)ccc2nc1-c1ccccc1
InChIKey: GCWKGSYISCSWKX-MRXNPFEDSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 363.42, ALogP 3.61, HBA 5, HBD 1, PSA 75.55, QED 0.75
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCC[C@@H]3CO)nc2c1
InChIKey: RSHYJNDBLZXSLE-OAHLLOKOSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 349.39, ALogP 2.96, HBA 5, HBD 2, PSA 86.55, QED 0.75
Compound (SMILES): CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccc(F)cc1
InChIKey: JKKRYYTVQXUOKL-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 339.37, ALogP 3.98, HBA 4, HBD 1, PSA 66.32, QED 0.78
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCC[C@@H]3C(F)(F)F)nc2c1
InChIKey: UZOQISATLXPBPB-MRXNPFEDSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 387.36, ALogP 4.53, HBA 4, HBD 1, PSA 66.32, QED 0.72
Compound (SMILES): COc1ccc2c(c1)CCCN2c1nc2cc(C(=O)O)ccc2nc1-c1ccccc1
InChIKey: CALMFUDXDNPGQC-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 411.46, ALogP 5.09, HBA 5, HBD 1, PSA 75.55, QED 0.5
Compound (SMILES): CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccc(F)c(F)c1
InChIKey: ZWCJLTGYJAFRFZ-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 357.36, ALogP 4.12, HBA 4, HBD 1, PSA 66.32, QED 0.76
Compound (SMILES): CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccc(Cl)cc1
InChIKey: PWGUMJNASSFPEW-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 355.83, ALogP 4.49, HBA 4, HBD 1, PSA 66.32, QED 0.75
Compound (SMILES): CN(c1nc2cc(C(=O)O)ccc2nc1-c1ccccc1)C1CCCC1
InChIKey: BKUWVWJDONBNID-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 347.42, ALogP 4.37, HBA 4, HBD 1, PSA 66.32, QED 0.76
Compound (SMILES): C[C@H]1CCCN1c1nc2cc(C(=O)O)ccc2nc1-c1ccc(F)cc1
InChIKey: DZRUCRKWBXDZRX-LBPRGKRZSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 351.38, ALogP 4.12, HBA 4, HBD 1, PSA 66.32, QED 0.77
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccc(F)cc3)c(N3CCCCCC3)nc2c1
InChIKey: QYKVCCCMPASUMG-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 365.41, ALogP 4.51, HBA 4, HBD 1, PSA 66.32, QED 0.74
Compound (SMILES): CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1ccc2c(c1)OCO2
InChIKey: YRKANMKKKIUCMP-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 365.39, ALogP 3.57, HBA 6, HBD 1, PSA 84.78, QED 0.76
Compound (SMILES): COCC1CCCN(c2nc3cc(C(=O)O)ccc3nc2-c2ccc(F)cc2)C1
InChIKey: BESVKGQEYPPWDB-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 395.43, ALogP 4, HBA 5, HBD 1, PSA 75.55, QED 0.7
Compound (SMILES): CC1(C)CCCN(c2nc3cc(C(=O)O)ccc3nc2-c2ccc(F)cc2)C1
InChIKey: WFZHQPVGJAHSMC-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: PASK ATP Radiochemical Assay: Purified PASK (UniProt #Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (2 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 379.44, ALogP 4.76, HBA 4, HBD 1, PSA 66.32, QED 0.71