lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COCCS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC2CCC(F)(F)CC2)cc1F
InChIKey: IXRXQBRXBNTWPW-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 449.49, ALogP 3.61, HBA 5, HBD 1, PSA 81.7, QED 0.62
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC23CC4(F)CC(F)(CC(F)(C4)C2)C3)cc1F
InChIKey: IFRGFTQIIMWCJG-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 501.54, ALogP 4.8, HBA 4, HBD 1, PSA 72.47, QED 0.55
Compound (SMILES): CC(C)N1CCN(c2ccc(Nc3ncc4cc(C(=O)N(C)C)n(C5CCCC5)c4n3)nc2)CC1
InChIKey: XVVBHKGQHJECBA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: TR-FRET (Time-Resolved-Fluorescence Energy Transfer) Endpoint Assay: A 384-well microtiter Lance TR-FRET (time-resolved-fluorescence energy transfer) endpoint assay was used for CDK4/cyclin D1 kinase activity measurements. The same assay was used for IC50 determination of small molecule inhibitors. In general, the kinase reactions were carried out in 30 uL volumes in the reaction solution containing the following: 2 uL compound (in 20% DMSO), 18 uL CDK4/cyclin D1 in Assay Buffer (50 mM HEPES, pH 7.5, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.05% BSA, 0.02% Tween-20), 10 uL of the mixture of pRb152 and ATP. The final reaction mixture contains compound (inhibitor) with the concentration varying from 0.005-10 uM, 2% DMSO, 0.3 nM CDK4/cyclin D1, 175 nM pRb152, and 3 uM ATP (Amersham Pharmacia, Cat. No. 27-2056-01). All reactions were run at room temperature in 384-well white flat-bottom OptiPlates (Perkin Elmer, Cat. No. 6007290) for 60 min then were quenched by the addition of 10 uL of 120 mM EDTA.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 476.63, ALogP 3.92, HBA 8, HBD 1, PSA 82.42, QED 0.58
Compound (SMILES): CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(C(=O)CC5CCCCC5)CC4)cn3)nc2n1C1CCCC1
InChIKey: WSGVSDAVYRTGJF-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: IMAP-FPT (Molecular Devices Trade Mark Technology) Endpoint Assay: The assay was run under the conditions identical to that for CDK1/cyclin B except 0.25 nM CDK1/cyclin B was replaced with 0.3 nM CDK2/cyclin A. A 384-well microtiter IMAP-FPT (Molecular Devices Trade Mark Technology) endpoint assay was used for CDK1/cyclin B kinase activity measurements. The same assay was used for IC50 determination of small molecule inhibitors. In general, the kinase reactions were carried out in 20 μL volumes in the reaction solution, which is composed of 2 μL compound (in 20% DMSO), 8 μL CDK1/cyclin B in the 1× Reaction Buffer (Molecular Devices, Cat. No. R8139), 10 μL substrate mixture of Tamra Histone-H1 peptide (Molecular Devices, Cat. No. R7384) and ATP (Amersham Pharmacia, Cat. No. 27-2056-01) in the 1× Reaction Buffer with 1 mM DTT freshly added. The final reaction mixture contains compound (inhibitor) with the concentration varying from 0.005-10 μM, 2% DMSO, 0.25 nM CDK1/cyclin B, 100 nM Tamra Histone-H1 peptide, and 20 μM ATP.
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 558.73, ALogP 5.01, HBA 8, HBD 1, PSA 99.49, QED 0.44
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1CCc2nc(Nc3ccc(N4CCN(C)CC4)cc3)ncc2C1=O
InChIKey: WVGSOXRZIVSEQO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 615.66, ALogP 5.75, HBA 7, HBD 2, PSA 93.7, QED 0.29
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc3c(n2)CCN(c2cc(NC(=O)c4cc(C(F)(F)F)ccn4)ccc2Cl)C3)cc1
InChIKey: FLJSOYXRJCMRAE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: TR-FRET Assay: Compounds were screened in the TR-FRET assay for JAK2 and c-Src kinase inhibition. Ultra light poly GT (Perkin Elmer) was used as the substrate for JAK2 and c-Src with the ATP concentration of 10 μM and 50 μM, respectively. The Eu-labelled anti-phospho tyrosine antibody (Perkin Elmer) was added at 1 nM and the fluorescence emission at 615 nm and 665 nm was measured with an excitation wavelength of 340 nm.
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 581.99, ALogP 5.46, HBA 7, HBD 3, PSA 112.14, QED 0.28
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: ThermoFluor Assay: The ThermoFluor (TF) assay is a 384-well microplate-based binding assay that measures thermal stability of proteins1,2. The experiments were carried out using ThermoFluor instruments available from Johnson & Johnson Pharmaceutical Research & Development, LLC. TF dye used in all experiments was 1,8-ANS (Invitrogen: A-47). Final TF assay conditions used for MGL studies were 0.07 mg/ml of mutant MGL, 100 uM ANS, 200 mM NaCl, 0.001% Tween-20 in 50 mM PIPES (pH=7.0).Screening compound plates contained 100% DMSO compound solutions at a single concentration. For follow-up concentration-response studies, compounds were arranged in a pre-dispensed plate (Greiner Bio-one: 781280), wherein compounds were serially diluted in 100% DMSO across 11 columns within a series. Columns 12 and 24 were used as DMSO reference and contained no compound. For both single and multiple compound concentration-repsonse experiments, the compound aliquots (46 mL) were robotically predispensed directly into 384-well.
Measurement: Kd = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): COc1ncc(-c2nc3c(n2C(C)C)C(c2ccc(Cl)cc2)N(c2cc(Cl)cn(C)c2=O)C3=O)c(OC)n1
InChIKey: AGBSXNCBIWWLHD-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding affinity to human MDM2 assessed as inhibition constant
Measurement: IC50 = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 555.42, ALogP 4.69, HBA 9, HBD 0, PSA 104.37, QED 0.34
Compound (SMILES): COCc1cc(C#N)cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC)CC2)C3)c1
InChIKey: WXWZQOAPXMLOGN-HAOYJSTOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Diluted TR-FRET Assay: TR-FRET AssayThe beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 442.56, ALogP 4.49, HBA 6, HBD 1, PSA 92.99, QED 0.76
Compound (SMILES): COc1cccc(-c2ccc3c(c2)C2(CCO3)N=C(C)C(N)=N2)c1F
InChIKey: HZUBJQJZQJTUIS-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 339.37, ALogP 3.27, HBA 5, HBD 1, PSA 69.2, QED 0.91
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: CZRMENLRCXEIFA-GSBZAIBZSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 741.58, ALogP 10.63, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ncc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: SVVFIIYREHMBTN-UNCTUWKVSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin)
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 725.56, ALogP 9.28, HBA 6, HBD 1, PSA 101.85, QED 0.2
Compound (SMILES): CC1(C)C2CCC1(C)C(Oc1cc(F)c(C(=O)NS(C)(=O)=O)cc1Cl)C2
InChIKey: LOOOARQIFZVUEX-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 403.9, ALogP 3.76, HBA 4, HBD 1, PSA 72.47, QED 0.83
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(Cl)c(OCCC2CC2)cc1F
InChIKey: KXTGARHIVFGTKX-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -60 mV holding potential by whole-cell patch voltage clamp electrophysiology recording
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 335.78, ALogP 2.35, HBA 4, HBD 1, PSA 72.47, QED 0.87
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc(OCC23CC4CC(CC(C4)C2)C3)c(Cl)c1
InChIKey: VLKKFBQBPCTMAH-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating.
Measurement: IC50 = 38.6 nM (pChEMBL 7.409999847412109)
Descriptors: MW 397.92, ALogP 3.62, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(Cl)c(OCCC2CCCCC2)cc1F
InChIKey: PNQHUEIYIAWMIZ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 377.87, ALogP 3.52, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: FQHDBBOTIYOYLF-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Displacement of [3H]GX-545 from human Nav1.7 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit by liquid scintillation counting analysis
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 421.53, ALogP 3.99, HBA 4, HBD 1, PSA 72.47, QED 0.75
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: VENWKQHIOIEAII-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 447.57, ALogP 4.52, HBA 4, HBD 1, PSA 72.47, QED 0.67
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC23CC4CC(C2)C(F)(F)C(C4)C3)cc1F
InChIKey: MSLIEPIIAJYDTK-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 457.51, ALogP 4.23, HBA 4, HBD 1, PSA 72.47, QED 0.69
Compound (SMILES): O=C(NS(=O)(=O)N1CCCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: OZPDALRKJRELDR-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 1 hr in presence of veratridine and anthropleurin-C by sodium influx assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 476.61, ALogP 4.37, HBA 4, HBD 1, PSA 75.71, QED 0.63
Compound (SMILES): O=C(NS(=O)(=O)N1CCOCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: DEYOMPPOEBPYPT-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells incubated for 1 hr in presence of veratridine by sodium influx assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 492.61, ALogP 3.61, HBA 5, HBD 1, PSA 84.94, QED 0.63
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC2CCC(F)(F)CC2)cc1F
InChIKey: TXCVJBLHIKCNRG-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating.
Measurement: IC50 = 5230 nM (pChEMBL 5.28000020980835)
Descriptors: MW 405.44, ALogP 3.6, HBA 4, HBD 1, PSA 72.47, QED 0.79
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC2CCC(F)(F)CC2)cc1F
InChIKey: RQJYQECMAVLMJI-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 431.48, ALogP 4.13, HBA 4, HBD 1, PSA 72.47, QED 0.7
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Reversible inhibition of wild type human MAGL using 4-methylumbelliferyl butyrate as substrate measured after 5 mins by fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK2/cyclinA2 expressed in baculovirus infected Sf9 insect cells using histone H1 as substrate measured after 10 mins by ADP-glo assay
Measurement: IC50 = 3460 nM (pChEMBL 5.460000038146973)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): COc1ncc(-c2nc3c(n2C(C)C)C(c2ccc(Cl)cc2)N(c2cc(Cl)cn(C)c2=O)C3=O)c(OC)n1
InChIKey: AGBSXNCBIWWLHD-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Inhibition of human MDM4 by SRP assay
Measurement: IC50 = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 555.42, ALogP 4.69, HBA 9, HBD 0, PSA 104.37, QED 0.34
Compound (SMILES): COCc1cc(C#N)cc(-c2ccc3c(c2)C2(N=C(C)C(N)=N2)[C@]2(CC[C@H](OC)CC2)C3)c1
InChIKey: WXWZQOAPXMLOGN-HAOYJSTOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 15400 nM (pChEMBL 4.809999942779541)
Descriptors: MW 442.56, ALogP 4.49, HBA 6, HBD 1, PSA 92.99, QED 0.76
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: CZRMENLRCXEIFA-GSBZAIBZSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 741.58, ALogP 10.63, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ncc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: SVVFIIYREHMBTN-UNCTUWKVSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 287 nM (pChEMBL 6.539999961853027)
Descriptors: MW 725.56, ALogP 9.28, HBA 6, HBD 1, PSA 101.85, QED 0.2
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc(OCC23CC4CC(CC(C4)C2)C3)c(Cl)c1
InChIKey: VLKKFBQBPCTMAH-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 397.92, ALogP 3.62, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: FQHDBBOTIYOYLF-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 421.53, ALogP 3.99, HBA 4, HBD 1, PSA 72.47, QED 0.75
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(Cl)c(OCC2CC3C4CCC(C4)C3C2)cc1F
InChIKey: YTSQUJOXQNTPEU-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 415.91, ALogP 3.62, HBA 4, HBD 1, PSA 72.47, QED 0.8
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: VENWKQHIOIEAII-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells incubated for 1 hr in presence of veratridine by sodium influx assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 447.57, ALogP 4.52, HBA 4, HBD 1, PSA 72.47, QED 0.67
Compound (SMILES): O=C(NS(=O)(=O)N1CCOCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: DEYOMPPOEBPYPT-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 1 hr in presence of veratridine and anthropleurin-C by sodium influx assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 492.61, ALogP 3.61, HBA 5, HBD 1, PSA 84.94, QED 0.63
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC2CCC(F)(F)CC2)cc1F
InChIKey: TXCVJBLHIKCNRG-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 405.44, ALogP 3.6, HBA 4, HBD 1, PSA 72.47, QED 0.79
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH (unknown origin)
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) by Kinomescan method
Measurement: IC50 < 0.514 nM (pChEMBL 9.288999557495117)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: CZRMENLRCXEIFA-GSBZAIBZSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin)
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 741.58, ALogP 10.63, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc(OCC23CC4CC(CC(C4)C2)C3)c(Cl)c1
InChIKey: VLKKFBQBPCTMAH-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 397.92, ALogP 3.62, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: FQHDBBOTIYOYLF-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells incubated for 1 hr in presence of veratridine by sodium influx assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 421.53, ALogP 3.99, HBA 4, HBD 1, PSA 72.47, QED 0.75
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(Cl)c(OCC2CC3C4CCC(C4)C3C2)cc1F
InChIKey: YTSQUJOXQNTPEU-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 415.91, ALogP 3.62, HBA 4, HBD 1, PSA 72.47, QED 0.8
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: VENWKQHIOIEAII-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 1 hr in presence of veratridine and anthropleurin-C by sodium influx assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 447.57, ALogP 4.52, HBA 4, HBD 1, PSA 72.47, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Binding affinity to CB1 receptor (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin) by Kinomescan method
Measurement: IC50 = 584 nM (pChEMBL 6.230000019073486)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: FQHDBBOTIYOYLF-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 1 hr in presence of veratridine and anthropleurin-C by sodium influx assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 421.53, ALogP 3.99, HBA 4, HBD 1, PSA 72.47, QED 0.75
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding affinity to CB2 receptor (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) by Kinomescan method
Measurement: IC50 = 706 nM (pChEMBL 6.150000095367432)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL by fluorometric analysis
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin) by Kinomescan method
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Ceramide glucosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16739
Assay: Fluorometric Assay (Inhibition of 4MU-B cleavage)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) by Kinomescan method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Electrophysiological Assay: Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel alpha -subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37 C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating.
Measurement: IC50 = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: [3H] 2-OG cleavage activity assay (HeLa)
Measurement: IC50 = 1.13 nM (pChEMBL 8.949999809265137)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin) by Kinomescan method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Radioligand Binding Assay: Radioligand Binding Studies: Saturation experiments. A representative compound of formula (I) was tritiated. Three tritiums were incorporated in place of methyl hydrogens to generate [3H]compound. Binding of this radioligand was preformed in 5 mL borosilicate glass test tubes at room temperature. Binding was initiated by adding membranes to increasing concentrations of [3H]compound in 100 mM NaCl, 20 mM Tris HCl, pH 7.4 buffer containing 0.01% w/v bovine serum albumin (BSA) for 18 h. Non-specific binding was determined in the presence of 1 uM unlabelled compound. After 18 h, the reactants were filtered through GF/C glass fiber filters presoaked in 0.5% w/v polyethylene imine. Filters were washed with 15 mL ice cold 100 mM NaCl, 20 mM Tris HCl, pH7.4 buffer containing 0.25% BSA to separate bound from free ligand. [3H]compound bound to filters was quantified by liquid scintillation counting.Competitive binding experiments.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: [3H] 2-OG cleavage activity assay (PBMC)
Measurement: IC50 = 1.88 nM (pChEMBL 8.729999542236328)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44
Compound (SMILES): COC[C@@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-NJDAHSKKSA-N
Target: Cyclin-dependent kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: O94921
Assay: Inhibition of CDK14 (unknown origin) by Kinomescan method
Measurement: IC50 = 3450 nM (pChEMBL 5.460000038146973)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
InChIKey: PTCBNPULJWGSML-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 462.59, ALogP 3.98, HBA 4, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
InChIKey: IVOACCSOISMVBL-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Mus musculus
UniProt: O35678
Assay: [3H] 2-OG cleavage activity assay (mouse brain)
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 489.58, ALogP 3.51, HBA 6, HBD 0, PSA 61.68, QED 0.44