lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[n+]1c2ccccc2c(Nc2ccc(N3CCCCC3)cc2)c2[nH]c3ccccc3c21.[Cl-]
InChIKey: KKTYQIZMCZOJPP-UHFFFAOYSA-N
Target: Rhodesain (SINGLE PROTEIN), Trypanosoma brucei rhodesiense
UniProt: Q95PM0
Assay: Inhibition of Trypanosoma brucei rhodesiense rhodesain
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 407.54, ALogP 6.03, HBA 2, HBD 2, PSA 34.94, QED 0.36
Compound (SMILES): O=c1cc(OCc2ccccc2)ccn1-c1ccc2c(cnn2CCN2CC3CC2CO3)c1
InChIKey: RGLFFOVIUUFFFB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK cells by mini-patch clamp assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 442.52, ALogP 3.24, HBA 7, HBD 0, PSA 61.52, QED 0.44
Compound (SMILES): O=c1cc(OCc2ccccc2)ccn1-c1ccc2c(cnn2CCN2CCNCC2)c1
InChIKey: QQZPUNRRFIGWLK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK cells by mini-patch clamp assay
Measurement: IC50 = 16400 nM (pChEMBL 4.789999961853027)
Descriptors: MW 429.52, ALogP 2.67, HBA 7, HBD 1, PSA 64.32, QED 0.49
Compound (SMILES): Cc1[nH]c2ccc(OCc3ccccc3)cc2c1CCN
InChIKey: GXWTUBXFAHMHIY-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 receptor expressed in human T-REx-293 cells assessed as inhibition of icilin-induced 45calcium influx treated 5 mins before icilin challenge measured after 5 mins
Measurement: IC50 = 2360 nM (pChEMBL 5.630000114440918)
Descriptors: MW 280.37, ALogP 3.56, HBA 2, HBD 2, PSA 51.04, QED 0.75
Compound (SMILES): O=C(c1ccccc1)N1CCC(N2CCc3cc(O)ccc3C(O)C2)CC1
InChIKey: XZQGWQIWLXSEBC-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor guinea pig brain after 180 mins scintillation counting
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 366.46, ALogP 2.59, HBA 4, HBD 2, PSA 64.01, QED 0.86
Compound (SMILES): Oc1ccc2c(c1)CCN([C@H]1CC[C@@H](c3ccccc3)CC1)CC2O
InChIKey: GUYOIYKANZNIKE-RYKNDIGVSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Displacement of [3H]ifenprodil from human recombinant NR1-1a/NR2B receptor expressed in mouse L(tk-) cells after 120 mins by scintillation counting
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 337.46, ALogP 4.01, HBA 3, HBD 2, PSA 43.7, QED 0.87
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2ccccc2Cl)cc1)C(F)(F)F
InChIKey: HEYYMMKRFXWVJQ-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 364.77, ALogP 3.94, HBA 3, HBD 1, PSA 54.37, QED 0.9
Compound (SMILES): Cc1ccccc1S(=O)(=O)c1ccc(C(C)(O)C(F)(F)F)cc1
InChIKey: KSIDACILJMPROB-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 344.35, ALogP 3.6, HBA 3, HBD 1, PSA 54.37, QED 0.93
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2cccc(Cl)c2)cc1)C(F)(F)F
InChIKey: PBTLIUUMEYQLCW-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 317 nM (pChEMBL 6.5)
Descriptors: MW 364.77, ALogP 3.94, HBA 3, HBD 1, PSA 54.37, QED 0.9
Compound (SMILES): CC(C)(CNC(=O)C1CCCCO1)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: IWAGYADOEPALTO-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22001
Assay: Inhibition of human Kv1.3 ion channel expressed in CGE22 cells
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 473.57, ALogP 3.49, HBA 5, HBD 1, PSA 88.07, QED 0.69
Compound (SMILES): CC(C)(CNC(=O)CC1CCCCO1)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: UJNLDKMQRWCJGL-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22001
Assay: Inhibition of human Kv1.3 ion channel expressed in CGE22 cells
Measurement: IC50 = 1350 nM (pChEMBL 5.869999885559082)
Descriptors: MW 487.6, ALogP 3.88, HBA 5, HBD 1, PSA 88.07, QED 0.64
Compound (SMILES): COc1ccc(COC(=O)C2(c3ccc(I)cc3)CCNCC2)cc1.O=C(O)C(=O)O
InChIKey: UGQARFBUXNEOBH-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 2925 nM (pChEMBL 5.53000020980835)
Descriptors: MW 451.3, ALogP 3.66, HBA 4, HBD 1, PSA 47.56, QED 0.56
Compound (SMILES): O=C(O)C(=O)O.O=C(OCc1ccc([N+](=O)[O-])cc1)C1(c2ccc(I)cc2)CCNCC1
InChIKey: WHVLBSZWHJFUTO-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 1777 nM (pChEMBL 5.75)
Descriptors: MW 466.28, ALogP 3.56, HBA 5, HBD 1, PSA 81.47, QED 0.32
Compound (SMILES): CNC(=O)C(=O)C(C)NC(=O)c1ccc(OCc2ccccn2)c(C(F)(F)F)c1Cl
InChIKey: IKTYGNJRDVXHJL-UHFFFAOYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K by fluorescence assay
Measurement: IC50 = 46.8 nM (pChEMBL 7.329999923706055)
Descriptors: MW 443.81, ALogP 2.77, HBA 5, HBD 2, PSA 97.39, QED 0.64
Compound (SMILES): CC(NC(=O)c1ccc(OCc2ccccn2)c(C(F)(F)F)c1Cl)C(=O)C(=O)N(C)C
InChIKey: LWCKGFHIVSAQMU-UHFFFAOYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 457.84, ALogP 3.11, HBA 5, HBD 1, PSA 88.6, QED 0.65
Compound (SMILES): COc1ccc2[nH]c3c(c2c1)CCN=C3c1ccccc1
InChIKey: QSEXKDCOIRWKGQ-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus Sortase A
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 276.34, ALogP 3.57, HBA 2, HBD 1, PSA 37.38, QED 0.76
Compound (SMILES): [N-]=[N+]=NCC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(=O)O)=C[C@@H]1O
InChIKey: OLOYDWMIOMMPCV-NCJYIMSCSA-N
Target: Sialidase-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQ49
Assay: Inhibition of human neuraminidase 3 assessed as inhibition of 4-methylumbelliferyl-alpha-D-glucopyranoside hydrolysis by fluorescence assay
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 332.27, ALogP -2.78, HBA 8, HBD 6, PSA 205.31, QED 0.16
Compound (SMILES): CC(C)c1nc(C(=O)N2CCOC3(CCN(Cc4ccc(Cl)cc4)CC3)C2)cs1
InChIKey: WBBYBFVZVFEOLK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 434.01, ALogP 4.43, HBA 5, HBD 0, PSA 45.67, QED 0.72
Compound (SMILES): CC(C)c1nc(C(=O)N2CCOC3(CCN(Cc4ccccc4)CC3)C2)cs1
InChIKey: MGWLEIOWCHHXGB-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 399.56, ALogP 3.77, HBA 5, HBD 0, PSA 45.67, QED 0.79
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(Cl)c2)C(=S)N1c1cccc(S(N)(=O)=O)c1
InChIKey: TYWODBAOGMISNZ-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR in human bicalutamide-resistant LNCAP cells assessed as inhibition of cell proliferation after 6 days
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 434.93, ALogP 2.78, HBA 5, HBD 1, PSA 107.5, QED 0.74
Compound (SMILES): CC(C)(NC(=O)COc1ccc2[nH]c(=O)c(-c3cccnc3)c(CCc3ccccc3)c2c1)c1ccccc1
InChIKey: XDSPDXZCQDPZCX-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 517.63, ALogP 5.81, HBA 4, HBD 2, PSA 84.08, QED 0.26
Compound (SMILES): CNC(=O)c1ccccc1Sc1ccc2c(/C=C/c3ccccn3)n[nH]c2c1
InChIKey: RITAVMQDGBJQJZ-FMIVXFBMSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Binding constant for TRKC kinase domain
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 386.48, ALogP 4.64, HBA 4, HBD 2, PSA 70.67, QED 0.52
Compound (SMILES): CC(C)(C)OC(=O)N[C@@H](CCCCCC(=O)NO)C(=O)NC1CCCC1
InChIKey: YKINZQJOQFMNPU-AWEZNQCLSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using Boc-Lys(Ac)-AMC as substrate by fluorometric analysis
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 371.48, ALogP 2.39, HBA 5, HBD 4, PSA 116.76, QED 0.28
Compound (SMILES): FC(F)(F)c1ccc(Nc2nc(N3CCNCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: DHTPCPXEBHJGGR-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Antagonist activity at rat TRPV1 expressed in HEK293 cells assessed as inhibition of capsaicin-induced intracellular Ca2+ level by FLIPR assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 537.51, ALogP 4.67, HBA 7, HBD 2, PSA 69.21, QED 0.47
Compound (SMILES): CC(C)c1nc2c(c(Nc3ccc(C(F)(F)F)cn3)n1)CCN(c1ncccc1C(F)(F)F)CC2
InChIKey: NACDTTPBPBGLSZ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Functional Assay: HEK293 cells were transfected with human TRPV1 cloned in pcDNA3.1zeo(+) using the Effectene non-liposomal lipid based transfection kit (Qiagen) (hTRPV1/HEK293). hTRPV1/HEK293 cells were routinely grown as monolayers under selection in zeocin (200 μg/mL; Invitrogen) in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, and penicillin/streptomycin (50 units/mL) in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 496.46, ALogP 5.78, HBA 6, HBD 1, PSA 66.83, QED 0.46
Compound (SMILES): CN(C)S(=O)(=O)c1ccc(Nc2nc(N3CCOCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: VBXZFCCNNSNIRY-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Functional Assay: HEK293 cells were transfected with human TRPV1 cloned in pcDNA3.1zeo(+) using the Effectene non-liposomal lipid based transfection kit (Qiagen) (hTRPV1/HEK293). hTRPV1/HEK293 cells were routinely grown as monolayers under selection in zeocin (200 μg/mL; Invitrogen) in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, and penicillin/streptomycin (50 units/mL) in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 577.63, ALogP 3.33, HBA 9, HBD 1, PSA 103.79, QED 0.47
Compound (SMILES): FC(F)(F)c1ccc(Nc2ncnc3c2CCN(c2ncccn2)CC3)cc1
InChIKey: KTLSTXOTTQMHEI-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 386.38, ALogP 3.63, HBA 6, HBD 1, PSA 66.83, QED 0.74
Compound (SMILES): O=C1O[C@]2(CC[C@H](c3nc4cc(C(F)(F)F)ccc4[nH]3)CC2)CN1c1ccccn1
InChIKey: GUXLIRBXKZUWHG-UWELNFAVSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonistic activity at human alpha1A receptor expressed in rat 1 fibroblast cells assessed as inhibition of calcium level by FLIPR assay
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 416.4, ALogP 5.03, HBA 4, HBD 1, PSA 71.11, QED 0.64
Compound (SMILES): CCOC(=O)NCCc1c[nH]c2ccc(OCc3ccccc3)cc12
InChIKey: DWBJTMILCRPGBU-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 receptor expressed in human T-REx-293 cells assessed as inhibition of icilin-induced 45calcium influx treated 5 mins before icilin challenge measured after 5 mins
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 338.41, ALogP 4.04, HBA 3, HBD 2, PSA 63.35, QED 0.68
Compound (SMILES): Cc1cccc(COc2ccccc2C(=O)N(CCCN)Cc2cccs2)c1
InChIKey: LCQJRANJHOEQFG-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8R455
Assay: Antagonist activity at rat TRPM8 expressed in HEK293 cells assessed as inhibition of menthol-induced calcium flux preincubated for 60 mins followed by menthol addition by Fluo-4 NW dye based fluorimetric method
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 394.54, ALogP 4.63, HBA 4, HBD 1, PSA 55.56, QED 0.58
Compound (SMILES): Oc1ccc2c(c1)CCN([C@H]1CC[C@H](c3ccccc3)CC1)CC2O
InChIKey: GUYOIYKANZNIKE-NRCGHCQOSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor guinea pig brain after 180 mins scintillation counting
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 337.46, ALogP 4.01, HBA 3, HBD 2, PSA 43.7, QED 0.87
Compound (SMILES): O=C(CCCN1CCc2cc(O)ccc2C(O)C1)c1ccc(F)cc1
InChIKey: LEBXQVNFNPRKSC-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor guinea pig brain after 180 mins scintillation counting
Measurement: Ki = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 343.4, ALogP 3.09, HBA 4, HBD 2, PSA 60.77, QED 0.82
Compound (SMILES): COc1ccc(S(=O)(=O)c2ccc(C(C)(O)C(F)(F)F)cc2)cc1
InChIKey: OJSGXLSONZGABF-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 229 nM (pChEMBL 6.639999866485596)
Descriptors: MW 360.35, ALogP 3.3, HBA 4, HBD 1, PSA 63.6, QED 0.91
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2ccc(F)cc2)cc1)C(F)(F)F
InChIKey: JKJZGYCRJXNWCU-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 348.32, ALogP 3.43, HBA 3, HBD 1, PSA 54.37, QED 0.68
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2ccc([N+](=O)[O-])cc2)cc1)C(F)(F)F
InChIKey: AZFKXBDELQNCEH-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 375.32, ALogP 3.2, HBA 5, HBD 1, PSA 97.51, QED 0.65
Compound (SMILES): CC(C)S(=O)(=O)N[C@H]1CN(C)C[C@@H]1c1ccc(-c2cccc(NS(C)(=O)=O)c2)cc1
InChIKey: RFQLQHFUQMZUSO-RTWAWAEBSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human hERG
Measurement: IC50 = 31600 nM (pChEMBL 4.5)
Descriptors: MW 451.61, ALogP 2.45, HBA 5, HBD 2, PSA 95.58, QED 0.67
Compound (SMILES): CC(C)(CNC(=O)C1CCOCC1(C)C)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: QAEOUQFGAJVUDB-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P22460
Assay: Inhibition of human Kv1.5 ion channel expressed in CHO K1 cells
Measurement: IC50 = 960 nM (pChEMBL 6.019999980926514)
Descriptors: MW 501.62, ALogP 3.99, HBA 5, HBD 1, PSA 88.07, QED 0.65
Compound (SMILES): CC(C)(CNC(=O)C1(C#N)CCOCC1)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: DRZGUYAHIWXYDK-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P22460
Assay: Inhibition of human Kv1.5 ion channel expressed in CHO K1 cells
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 498.58, ALogP 3.24, HBA 6, HBD 1, PSA 111.86, QED 0.65
Compound (SMILES): O=C(O)C(=O)O.O=C(OCc1ccc(Cl)c(Cl)c1)C1(c2ccc(I)cc2)CCNCC1
InChIKey: CJZABXVCLKCYJQ-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 4342 nM (pChEMBL 5.360000133514404)
Descriptors: MW 490.17, ALogP 4.96, HBA 3, HBD 1, PSA 38.33, QED 0.49
Compound (SMILES): COc1ccc(COC(=O)C2(c3ccc4ccccc4c3)CCNCC2)cc1.O=C(O)C(=O)O
InChIKey: RXXYPRWTIBZASG-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 889 nM (pChEMBL 6.050000190734863)
Descriptors: MW 375.47, ALogP 4.21, HBA 4, HBD 1, PSA 47.56, QED 0.68
Compound (SMILES): Oc1cccc(-c2cc(Nc3ccc4[nH]ncc4c3)nc(N3CCOCC3)n2)c1
InChIKey: OUULCVQTKHSXBK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 388.43, ALogP 3.31, HBA 7, HBD 3, PSA 99.19, QED 0.49
Compound (SMILES): c1ccc(CNc2ccnc3oc4ccccc4c23)cc1
InChIKey: UHJXGMZSUQNCOU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of VEGFR3
Measurement: Ki = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 274.32, ALogP 4.59, HBA 3, HBD 1, PSA 38.06, QED 0.59
Compound (SMILES): c1ccc(CCNc2ccnc3oc4ccccc4c23)cc1
InChIKey: YJPUSOPMLUPRJT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of VEGFR3
Measurement: Ki = 9390 nM (pChEMBL 5.03000020980835)
Descriptors: MW 288.35, ALogP 4.64, HBA 3, HBD 1, PSA 38.06, QED 0.59
Compound (SMILES): CC(C)c1nc(C(=O)N2CCOC3(CCN(Cc4ccccc4Cl)CC3)C2)cs1
InChIKey: WJZLXGFMQGCPSN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 434.01, ALogP 4.43, HBA 5, HBD 0, PSA 45.67, QED 0.72
Compound (SMILES): CC(C)c1nc(C(=O)N2CCOC3(CCN(Cc4cccc(Cl)c4)CC3)C2)cs1
InChIKey: GPARJKKXMHOXEG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 434.01, ALogP 4.43, HBA 5, HBD 0, PSA 45.67, QED 0.72
Compound (SMILES): CS(=O)(=O)c1cc(F)cc2c3c(n(Cc4ccc(Cl)cc4)c12)C(CC(=O)O)CCC3
InChIKey: USPFQIRXYBZUPX-UHFFFAOYSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Antagonist activity at prostanoid TP receptor
Measurement: Ki = 2.51 nM (pChEMBL 8.600000381469727)
Descriptors: MW 449.93, ALogP 4.78, HBA 4, HBD 1, PSA 76.37, QED 0.61
Compound (SMILES): CS(=O)(=O)c1ccc(-c2ccc([C@H](N[C@@H](CC3CC3)C(=O)N[C@H](C#N)Cc3ccccc3)C(F)(F)F)cc2)cc1
InChIKey: JNRFQDUMCHRUFL-MYKRZTLLSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human Cat B in HepG2 cells
Measurement: IC50 = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 569.65, ALogP 5.37, HBA 5, HBD 2, PSA 99.06, QED 0.32
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1cccc(S(N)(=O)=O)c1
InChIKey: SEQMPXNPBNAKCA-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR in human bicalutamide-resistant LNCAP cells assessed as inhibition of cell proliferation after 6 days
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 468.48, ALogP 3.14, HBA 5, HBD 1, PSA 107.5, QED 0.69
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(Cl)c2)C(=S)N1c1cccc(S(N)(=O)=O)n1
InChIKey: BPEAQTOVXXWKSB-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR in human bicalutamide-resistant LNCAP cells assessed as inhibition of cell proliferation after 6 days
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 435.92, ALogP 2.17, HBA 6, HBD 1, PSA 120.39, QED 0.73
Compound (SMILES): O=C(COc1ccc2[nH]c(=O)c(-c3nccs3)c(CCc3ccccc3)c2c1)NC1(c2ccccc2)CC1
InChIKey: MKBNUPBFSAAINL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]ZM241385 from human adenosine A2B receptor transfected in CHO cells after 60 mins by scintillation counting
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 521.64, ALogP 5.62, HBA 5, HBD 2, PSA 84.08, QED 0.26
Compound (SMILES): CC(C)(NC(=O)COc1ccc2[nH]c(=O)c(-c3ccncc3)c(CCc3ccccc3)c2c1)c1ccccc1
InChIKey: ZWFIJURLONJRJJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki = 884 nM (pChEMBL 6.050000190734863)
Descriptors: MW 517.63, ALogP 5.81, HBA 4, HBD 2, PSA 84.08, QED 0.26
Compound (SMILES): O=C(c1ccccc1N1Cn2c(ccc2-c2ccccc2)C1=O)N1CCCCC1
InChIKey: KHHBKFYFMHFBOI-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.47, ALogP 4.4, HBA 3, HBD 0, PSA 45.55, QED 0.67
Compound (SMILES): CC(=O)c1cc2ccc(=O)oc2cc1OCc1ccccc1
InChIKey: KGCGFZVCFSWNLQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of full length human CA2 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 294.31, ALogP 3.57, HBA 4, HBD 0, PSA 56.51, QED 0.54
Compound (SMILES): FC(F)(F)c1ccc(Nc2nc(N3CCCCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)nc1
InChIKey: BMFWQCIOYBOEMD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 537.51, ALogP 5.64, HBA 7, HBD 1, PSA 70.07, QED 0.43
Compound (SMILES): FC(F)(F)c1ccc(Nc2ncnc3c2CCN(c2ncccc2Cl)CC3)cc1
InChIKey: BHSLYPQDMMBFGB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 419.84, ALogP 4.89, HBA 5, HBD 1, PSA 53.94, QED 0.65
Compound (SMILES): CS(=O)(=O)c1cccnc1N1CCc2ncnc(Nc3ccc(C(F)(F)F)cc3)c2CC1
InChIKey: JVAQUSIYGAKOLL-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 8520 nM (pChEMBL 5.070000171661377)
Descriptors: MW 463.49, ALogP 3.64, HBA 7, HBD 1, PSA 88.08, QED 0.63
Compound (SMILES): N#Cc1ccc2[nH]c([C@H]3CC[C@]4(CC3)CN(c3ccccc3)C(=O)O4)nc2c1
InChIKey: VJDPCRVAZYFIDE-CIEDQVTBSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay
Measurement: Ki = 0.3162 nM (pChEMBL 9.5)
Descriptors: MW 372.43, ALogP 4.49, HBA 4, HBD 1, PSA 82.01, QED 0.72
Compound (SMILES): N#Cc1ccc2[nH]c([C@H]3CC[C@]4(CC3)CN(c3ccc(F)cc3)C(=O)O4)nc2c1
InChIKey: UXCIUAMOIHCLOR-VVONHTQRSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay
Measurement: Ki = 0.631 nM (pChEMBL 9.199999809265137)
Descriptors: MW 390.42, ALogP 4.63, HBA 4, HBD 1, PSA 82.01, QED 0.69
Compound (SMILES): O=c1cc(-c2ccc(C(F)(F)F)cc2)ccn1-c1ccc2c(cnn2CCN2CCCC2)c1
InChIKey: RMUWRXSDAOJENI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 452.48, ALogP 4.97, HBA 5, HBD 0, PSA 43.06, QED 0.43
Compound (SMILES): OC1CN(CCCCc2ccccc2)CCc2cc(OCc3ccccc3)ccc21
InChIKey: IVXXSCFPBJLDFZ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor guinea pig brain after 180 mins scintillation counting
Measurement: Ki = 293 nM (pChEMBL 6.53000020980835)
Descriptors: MW 401.55, ALogP 5.18, HBA 3, HBD 1, PSA 32.7, QED 0.53
Compound (SMILES): OC1CN(CCCOc2ccccc2)CCc2cc(OCc3ccccc3)ccc21
InChIKey: MUPLYZRZMPPYMK-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor guinea pig brain after 180 mins scintillation counting
Measurement: Ki = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 403.52, ALogP 4.63, HBA 4, HBD 1, PSA 41.93, QED 0.56
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2ccccc2F)cc1)C(F)(F)F
InChIKey: DVQLPEBKURWLLN-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 348.32, ALogP 3.43, HBA 3, HBD 1, PSA 54.37, QED 0.86
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)c2ccccc2C(F)(F)F)cc1)C(F)(F)F
InChIKey: OPECELRZYKHDRT-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 398.32, ALogP 4.31, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CCc1ccccc1S(=O)(=O)c1ccc(C(C)(O)C(F)(F)F)cc1
InChIKey: BKJONPBKARADED-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of human 11beta-HSD1 transfected in HEK293 cells by scintillation proximity assay
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 358.38, ALogP 3.85, HBA 3, HBD 1, PSA 54.37, QED 0.9
Compound (SMILES): CCN1C[C@H](NS(=O)(=O)C(C)C)[C@@H](c2ccc(-c3cccc(NS(C)(=O)=O)c3)cc2)C1
InChIKey: WFNJLQOIUGZSCZ-YADHBBJMSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human hERG
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 465.64, ALogP 2.84, HBA 5, HBD 2, PSA 95.58, QED 0.63
Compound (SMILES): CC(C)N1C[C@H](NS(=O)(=O)C(C)C)[C@@H](c2ccc(-c3cccc(NS(C)(=O)=O)c3)cc2)C1
InChIKey: XTJHZPUPANMRKY-PKTZIBPZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human hERG
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 479.67, ALogP 3.23, HBA 5, HBD 2, PSA 95.58, QED 0.61
Compound (SMILES): CC(C)(CNC(=O)C1(O)CCOCC1)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: NGLQQPMSIMWKDI-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P22460
Assay: Inhibition of human Kv1.5 ion channel expressed in CHO K1 cells
Measurement: IC50 = 1980 nM (pChEMBL 5.699999809265137)
Descriptors: MW 489.57, ALogP 2.47, HBA 6, HBD 2, PSA 108.3, QED 0.65
Compound (SMILES): Cn1cccc1CC(=O)NCC(C)(C)CN(C1=NS(=O)(=O)c2cc(F)ccc21)c1ccccc1
InChIKey: FOYXDHFHQOJUSI-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22001
Assay: Inhibition of human Kv1.3 ion channel expressed in CGE22 cells
Measurement: IC50 = 2560 nM (pChEMBL 5.590000152587891)
Descriptors: MW 482.58, ALogP 3.5, HBA 5, HBD 1, PSA 83.77, QED 0.56
Compound (SMILES): O=C(O)C(=O)O.O=C(OCc1ccc([N+](=O)[O-])cc1)C1(c2ccc3ccccc3c2)CCNCC1
InChIKey: PLNZPDSXRCJCRD-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 732 nM (pChEMBL 6.130000114440918)
Descriptors: MW 390.44, ALogP 4.11, HBA 5, HBD 1, PSA 81.47, QED 0.4
Compound (SMILES): O=C(O)C(=O)O.O=C(OCc1ccc(Cl)c(Cl)c1)C1(c2ccc3ccccc3c2)CCNCC1
InChIKey: SXNNAHDOPPUABC-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35428 from dopamine transporter in Sprague-Dawley rat brain after 1 hr by liquid scintillation counting
Measurement: Ki = 3212 nM (pChEMBL 5.489999771118164)
Descriptors: MW 414.33, ALogP 5.51, HBA 3, HBD 1, PSA 38.33, QED 0.57
Compound (SMILES): c1ccc2c(CNc3ccnc4oc5ccccc5c34)cccc2c1
InChIKey: YYQLLFCNZXWBJQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of VEGFR3
Measurement: Ki = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 324.38, ALogP 5.75, HBA 3, HBD 1, PSA 38.06, QED 0.46
Compound (SMILES): COc1ccc(CNc2ccnc3oc4ccccc4c23)cc1
InChIKey: MNMQBQOLMHVBJT-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of recombinant human GST-tagged IGF1R expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate after 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 304.35, ALogP 4.6, HBA 4, HBD 1, PSA 47.29, QED 0.6
Compound (SMILES): Cc1ccccc1CN1CCC2(CC1)CN(C(=O)c1csc(C(C)C)n1)CCO2
InChIKey: BWSIBMJVLHAOKJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 413.59, ALogP 4.08, HBA 5, HBD 0, PSA 45.67, QED 0.76
Compound (SMILES): Cc1nc(C(=O)N2CCCC3(CCN(Cc4ccc(Cl)cc4)CC3)C2)cs1
InChIKey: FXYMZHCQKFWAQZ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHO-K1 cells after 16 hrs by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 403.98, ALogP 4.62, HBA 4, HBD 0, PSA 36.44, QED 0.75
Compound (SMILES): C[C@@H](c1ccc(Cl)cc1)n1c2c(c3cc(F)cc(S(C)(=O)=O)c31)CCC[C@@H]2CC(=O)O
InChIKey: SSLHBZFYMFYOLS-DZGCQCFKSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Antagonist activity at prostanoid TP receptor
Measurement: Ki = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 463.96, ALogP 5.34, HBA 4, HBD 1, PSA 76.37, QED 0.55
Compound (SMILES): C[C@@H](c1ccc(Cl)c(F)c1)n1c2c(c3cc(F)cc(S(C)(=O)=O)c31)CCC[C@@H]2CC(=O)O
InChIKey: PZOJAPPZAXUOPF-GXTWGEPZSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Antagonist activity at prostanoid TP receptor
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 481.95, ALogP 5.48, HBA 4, HBD 1, PSA 76.37, QED 0.52
Compound (SMILES): CS(=O)(=O)c1ccc(-c2ccc([C@H](N[C@@H](CC(Cl)Cl)C(=O)N[C@H](C#N)Cc3ccccc3)C(F)(F)F)cc2)cc1
InChIKey: UULSCOLFHVNVPK-GVUKDKGQSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human Cat B in HepG2 cells
Measurement: IC50 = 383 nM (pChEMBL 6.420000076293945)
Descriptors: MW 612.5, ALogP 5.76, HBA 5, HBD 2, PSA 99.06, QED 0.27
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1cccc(S(N)(=O)=O)n1
InChIKey: JIIHFLNYGVNTFP-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR in human bicalutamide-resistant LNCAP cells assessed as inhibition of cell proliferation after 6 days
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 469.47, ALogP 2.54, HBA 6, HBD 1, PSA 120.39, QED 0.69
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccnc(S(N)(=O)=O)c1
InChIKey: FJTVLRBKLVJPNG-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR in human bicalutamide-resistant LNCAP cells assessed as inhibition of cell proliferation after 6 days
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 469.47, ALogP 2.54, HBA 6, HBD 1, PSA 120.39, QED 0.69