lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: KVJYMIYOBIVPHB-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as reduction in IFNalpha induced STAT1 phosphorylation preincubated for 30 mins followed by IFNalpha addition and measured after 20 mins by flow cytometer analysis
Measurement: IC50 = 478 nM (pChEMBL 6.320000171661377)
Descriptors: MW 470.49, ALogP 2.95, HBA 10, HBD 1, PSA 131.08, QED 0.47
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8/CyclinC (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: AMPK alpha2/beta1/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y478
Assay: Inhibition of human AMPK alpha2/beta1/gamma1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): COc1ccc2c(c1)CNc1nc(nc3c(C(C)C)cnn13)NCC1(CCCCCO2)CCNCC1
InChIKey: QXSFYRZUNKRXIV-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis
Measurement: IC50 = 297 nM (pChEMBL 6.53000020980835)
Descriptors: MW 493.66, ALogP 4.6, HBA 9, HBD 3, PSA 97.63, QED 0.48
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclinH/MAT1 (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 197 nM (pChEMBL 6.710000038146973)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: AMPK alpha2/beta1/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54646
Assay: Inhibition of human AMPK alpha2/beta1/gamma1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): COc1ccc(Cc2cn[nH]c2)nc1-c1cccc([N+](=O)[O-])c1
InChIKey: CCLBPIKWQKSPNY-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B1 S133D mutant by coupled enzyme based fluorescence analysis
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 310.31, ALogP 2.98, HBA 5, HBD 1, PSA 93.94, QED 0.58
Compound (SMILES): CN1CCC[C@H]1Cc1c[nH]c2cccc(OCc3ccccc3)c12
InChIKey: FQTZZHAWEBFBAW-SFHVURJKSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: i. Prepare the assay buffer following the table below;Reagent ConcentrationTris 50 mMCaCl2  4 mMBSA 0.1% (w/v)Adjust pH to 7.4 followed by 0.2 μM sterile filtrationii. Preparation of 8 doses of reference and exemplary test compounds starting from 10 mM stock solution as requested by 5-fold serial dilutions with 100%;iii. Prepare (v/v) DMSO: a. Add 50 μl/well of 0.5% (v/v) PEI to UniFilter-96 GF/B plates. Seal the plates and incubate at 4° C. for 3 hrs; b. After incubation, wash the plates 3 times with ice-cold wash buffer (50 mM Tris, pH7.4);iv. Preparation of assay plates: a. Dilute cell membrane with assay buffer and add 330 μl/well to 96 round deep well plates to reach a concentration of 20 μg/well; b. Prepare 8 concentrations of reference or exemplary test compounds and add 110 μl/well to 96 round deep well plates; c. Dilute [3H]-ketanserin with assay buffer to 5 nM (5× final concentration) and add 110 μl/well to 96 round deep well plates.v. Centrifuge the plate at 1000 rpm for 30 secs and then agitate at 600 rpm, R.T. for 5 min.vi. Seal the plates and incubate the plate at 27° C. for 90 min.vii. Stop the incubation by vacuum filtration onto GF/B filter plates followed by 4 times washing with ice-cold wash buffer (50 mM Tris, pH7.4).vii. Dry the plates at 37° C. for 45 min.ix. Seal the filter plates and add 40 μl/well of scintillation cocktail.x. Read the plate by using a Microbeta2 microplate counter.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 320.44, ALogP 4.38, HBA 2, HBD 1, PSA 28.26, QED 0.76
Compound (SMILES): CC(C)(O)c1coc(S(=O)(=O)NC(=O)NC2c3ccccc3-c3ccccc32)c1
InChIKey: YMHREFTZPHZGRZ-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome pathway in human THP-1 cells assessed as LPS-stimulated IL-1beta release pretreated with LPS for 3 hrs followed by compound addition for 30 mins prior to MSU addition and measured after 30 mins by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 412.47, ALogP 3.26, HBA 5, HBD 3, PSA 108.64, QED 0.61
Compound (SMILES): Cc1ccc(-c2ccc3cc(OC[C@H](O)CF)ccc3n2)cn1
InChIKey: FBXCMFBJUZVBJS-OAHLLOKOSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Binding affinity to recombinant MAO-B (unknown origin) assessed as dissociation constant
Measurement: Kd = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 312.34, ALogP 3.31, HBA 4, HBD 1, PSA 55.24, QED 0.79
Compound (SMILES): OCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: FJLDXKYVYZQADI-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 426.37, ALogP 4.28, HBA 6, HBD 1, PSA 77.61, QED 0.41
Compound (SMILES): COc1ccc(-c2cc(Nc3ccc(C)cc3)c3ccccc3n2)cc1
InChIKey: LZXOHHMBMFDSTJ-UHFFFAOYSA-N
Target: Low molecular weight phosphotyrosine protein phosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: P24666
Assay: LMPTP Primary Screening Protocol: A listing of materials is provided:    Item, source, catalog no.    LMPTP-A Enzyme Stock Solution (4.22 mg/ml or 206.8 μM), SBMRI Protein Facility,    N/A    OMFP, Sigma, M2629-100 MG    Bis-Tris pH 6.0, Fisher Sci, BP301-100    Triton-X 100, Sigma, T9284    DTT, Sigma, D9779    Mol. Grade Water, Mediatech, Inc., 46-000-CM    1536-well black High base opaque bottom plate, Nexus Biosystems, 00019120Final assay conditions are:    0.625 nM LMPTP-A Enzyme    40 μM OMFP    50 mM Bis-Tris pH 6.0    1 mM DTT    0.01% Triton-X 100    20 μM test compound    3% DMSO (2% from substrate and 1% from compounds)    6 μL reaction volume    50 minutes incubation at room tempAssay Procedure    1. Prepare Reagents as described in section F. Recipe.    2. Using LabCyte Echo, transfer 60 nL from 2 mM test compound source plate into assay plate Col. 5-48 (final concentration of test compounds is 20 μM). 60 nL of DMSO should be transferred to col. 1-4 for positive and negative control wells.    3. Spin plates at 1000 rpm for 1 minute in centrifuge.    4. Using the Beckman Coulter Bioraptr, add 3 μL/well of control buffer to columns 1 and 2.    5. Using the Bioraptr, add 3 μL/well of enzyme solution to col. 3-48.    6. Using the Bioraptr, add 3 μL/well of substrate solution to col. 1-48.    7. Spin plates at 1000 rpm for 1 minute in centrifuge.    8. Incubate plates in the dark at room temperature for 50 minutes.    9. Read plates on PerkinElmer Viewlux using a FI protocol.
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 340.43, ALogP 5.96, HBA 3, HBD 1, PSA 34.15, QED 0.5
Compound (SMILES): CCOC(=O)Nc1nc2ccc(-c3cc(Cc4n[nH]c(=O)c5ccccc45)ccc3F)cc2[nH]1
InChIKey: DCSUGHIXMFUMOQ-UHFFFAOYSA-N
Target: Triosephosphate isomerase (SINGLE PROTEIN), Homo sapiens
UniProt: P60174
Assay: Inhibition of TPI (unknown origin)
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 457.47, ALogP 4.76, HBA 5, HBD 3, PSA 112.76, QED 0.35
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncccn2)CN1C(=O)c1ccnc(C(F)(F)F)c1F
InChIKey: ZRKGUMQBQFCLSZ-VIFPVBQESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7 receptor
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 407.33, ALogP 2.2, HBA 7, HBD 0, PSA 89.69, QED 0.61
Compound (SMILES): CN1CCC[C@@H]1Cc1c[nH]c2cccc(F)c12
InChIKey: ZXGSXBKTNNCUFJ-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: i. Prepare the assay buffer following the table below;Reagent ConcentrationTris 50 mMCaCl2  4 mMBSA 0.1% (w/v)Adjust pH to 7.4 followed by 0.2 μM sterile filtrationii. Preparation of 8 doses of reference and exemplary test compounds starting from 10 mM stock solution as requested by 5-fold serial dilutions with 100%;iii. Prepare (v/v) DMSO: a. Add 50 μl/well of 0.5% (v/v) PEI to UniFilter-96 GF/B plates. Seal the plates and incubate at 4° C. for 3 hrs; b. After incubation, wash the plates 3 times with ice-cold wash buffer (50 mM Tris, pH7.4);iv. Preparation of assay plates: a. Dilute cell membrane with assay buffer and add 330 μl/well to 96 round deep well plates to reach a concentration of 20 μg/well; b. Prepare 8 concentrations of reference or exemplary test compounds and add 110 μl/well to 96 round deep well plates; c. Dilute [3H]-ketanserin with assay buffer to 5 nM (5× final concentration) and add 110 μl/well to 96 round deep well plates.v. Centrifuge the plate at 1000 rpm for 30 secs and then agitate at 600 rpm, R.T. for 5 min.vi. Seal the plates and incubate the plate at 27° C. for 90 min.vii. Stop the incubation by vacuum filtration onto GF/B filter plates followed by 4 times washing with ice-cold wash buffer (50 mM Tris, pH7.4).vii. Dry the plates at 37° C. for 45 min.ix. Seal the filter plates and add 40 μl/well of scintillation cocktail.x. Read the plate by using a Microbeta2 microplate counter.
Measurement: EC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 232.3, ALogP 2.94, HBA 1, HBD 1, PSA 19.03, QED 0.84
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)cc2)CC1
InChIKey: WCAGCKMTLAATQU-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor extracted from HEK293 cell membrane assessed as inhibition constant incubated for 1 hrs by radioligand competitive binding based scintillation counter analysis
Measurement: Ki = 5495.41 nM (pChEMBL 5.260000228881836)
Descriptors: MW 383.92, ALogP 3.83, HBA 3, HBD 0, PSA 26.79, QED 0.78
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4ccc(OCCF)c(C(F)(F)F)c4)n3)cc2)C1
InChIKey: GBHNMMILYUXCPU-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 = 2.63 nM (pChEMBL 8.579999923706055)
Descriptors: MW 465.4, ALogP 4.29, HBA 6, HBD 1, PSA 88.69, QED 0.5
Compound (SMILES): Oc1cccc2[nH]cc(C[C@@H]3CCCN3)c12
InChIKey: PVFAYAZDVYXQFR-JTQLQIEISA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: i. Prepare the assay buffer following the table below;Reagent ConcentrationTris 50 mMCaCl2  4 mMBSA 0.1% (w/v)Adjust pH to 7.4 followed by 0.2 μM sterile filtrationii. Preparation of 8 doses of reference and exemplary test compounds starting from 10 mM stock solution as requested by 5-fold serial dilutions with 100%;iii. Prepare (v/v) DMSO: a. Add 50 μl/well of 0.5% (v/v) PEI to UniFilter-96 GF/B plates. Seal the plates and incubate at 4° C. for 3 hrs; b. After incubation, wash the plates 3 times with ice-cold wash buffer (50 mM Tris, pH7.4);iv. Preparation of assay plates: a. Dilute cell membrane with assay buffer and add 330 μl/well to 96 round deep well plates to reach a concentration of 20 μg/well; b. Prepare 8 concentrations of reference or exemplary test compounds and add 110 μl/well to 96 round deep well plates; c. Dilute [3H]-ketanserin with assay buffer to 5 nM (5× final concentration) and add 110 μl/well to 96 round deep well plates.v. Centrifuge the plate at 1000 rpm for 30 secs and then agitate at 600 rpm, R.T. for 5 min.vi. Seal the plates and incubate the plate at 27° C. for 90 min.vii. Stop the incubation by vacuum filtration onto GF/B filter plates followed by 4 times washing with ice-cold wash buffer (50 mM Tris, pH7.4).vii. Dry the plates at 37° C. for 45 min.ix. Seal the filter plates and add 40 μl/well of scintillation cocktail.x. Read the plate by using a Microbeta2 microplate counter.
Measurement: EC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 216.28, ALogP 2.17, HBA 2, HBD 3, PSA 48.05, QED 0.72
Compound (SMILES): OCCOCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: KBRMRLCSXVNEMV-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 = 15.4 nM (pChEMBL 7.809999942779541)
Descriptors: MW 470.42, ALogP 4.3, HBA 7, HBD 1, PSA 86.84, QED 0.31
Compound (SMILES): OCC(O)c1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: YDIJXZRZPRIWQQ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 = 23.8 nM (pChEMBL 7.619999885559082)
Descriptors: MW 412.34, ALogP 3.8, HBA 6, HBD 2, PSA 88.61, QED 0.57
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@H]5OC[C@]4(COP(=O)(O)O[C@@H]2[C@@H]3F)O[C@H]5n2cnc3c(N)ncnc32)c(=O)[nH]1
InChIKey: DKOKBVRVFOKJAR-JKRXGMIOSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: 3H-cGAMP Filtration Binding Assay (HAQ STING): The compounds were serially titrated by the Hamilton STARPlus CORE in a 96-well plate (Greiner, #651201) using a 1:3 ten-point dose response format. After compound preparation, a 2.2 ug/ml working concentration of STING membrane (SEQ. ID. No. 2) was prepared by diluting concentrated membrane into assay buffer (1×PBS; Invitrogen #SH30028.02) and douncing 7× using a manual tissue homogenizer (Wheaton, #357546). 148 uL of prepared membrane was then manually added to each well of a 96-well deep-well polypropylene plate (Fisher Scientific, #12-566-121). Following membrane addition, 2 uL of either titrated test compound, DMSO control (Sigma #276855), or cold cGAMP control (prepared in-house) was added to the appropriate wells using a Biomek FX. Compound and membrane then preincubated for 60 min at RT to allow compound binding to equilibrate. Following equilibration, 8 nM of [3H] c-GAMP ligand was prepared by diluting into assay buffer, and 50 uL of this working stock was then manually added to each well of the assay plate. Plates were then incubated at RT for 60 min, and the contents of each assay plate were then filtered through a 96-well GF/B filter plate (PerkinElmer, #6005250) using a TomTec MachIII Cell Harvester equipped with 20 mM HEPES buffer (Fisher Scientific, #BP299500). The filter plates were then dried at 55° C. for 30 min using a pressurized VWR oven before 30 uL of Ultima GoldF scintillate was added to each well. Tritium levels for each reaction well were then measured using a PerkinElmer TopCount plate reader.
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 688.42, ALogP -0.96, HBA 19, HBD 5, PSA 298.42, QED 0.16
Compound (SMILES): Cc1ccc([N+]2=Cc3c(c4ccccc4n3C)CC2)cc1
InChIKey: MFBLJEWYMXQAKA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) incubated for 40 mins by Ellman's method
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 275.37, ALogP 3.81, HBA 1, HBD 0, PSA 7.94, QED 0.6
Compound (SMILES): COC1CCC([C@@H](C)n2c(C)c(C(=O)NCc3c(SC)cc(C)[nH]c3=O)c3ccccc32)CC1
InChIKey: BSTSCQAGPZORCN-QHGAOEGBSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: EZH2 biochemical assay (IC50): Compound potencies were assessed through incorporation of 3H-SAM into a biotinylated H3 peptide. Specifically, 30 pM PRC2 containing wt EZH2 (pentameric complex prepared in-house) was pre-incubated with 450 nM SAM, 450 nM 3H-SAM, 2 μM H3K27me3 activating peptide (H2N-RKQLATKAAR(Kme3)SAPATGGVKKP-amide) and compounds (as 10 point duplicate dose response titrations in DMSO, final assay 0.8% DMSO (v/v)) for 3-5 h in 50 mM Tris (pH 8.5), 1 mM DTT, 0.07 mM Brij-35, 0.1% BSA, and 0.8% DMSO in a total volume of 12.5 μl. Reaction was initiated with biotinylated H3 substrate peptide (H2N-RKQLATKAAR(Kme1)SAPATGGVKKP-NTPEGBiot) as a 2 μM stock in 12.5 μl of buffer and allowed to react at room temperature for 18-22 h. Quenching was accomplished by addition of 20 μl of STOP solution (50 mM Tris (pH 8.5), 200 mM EDTA, 2 mM SAH). 35 μl of the quenched solution was transferred to streptavidin coated FlashPlates (PerkinElmer), incubated 1-2 h, washed, and read in a TopCount Reader (PerkinElmer). IC50s were calculated in Genedata Screener using non-linear least square four parameter fits, where the four parameters were IC50, Hill slope, pre-transitional baseline (0% INH), and post-transitional baseline (100% INH).
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 481.66, ALogP 5.36, HBA 5, HBD 2, PSA 76.12, QED 0.45
Compound (SMILES): OCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: MHXTXRZADPVWNK-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 382.31, ALogP 4.26, HBA 5, HBD 1, PSA 68.38, QED 0.65
Compound (SMILES): CCC(CC)(NC(=O)c1ccc(N2CC(OC)C2)c(OC[C@H]2C[C@@H]2CO)n1)C(=O)OCCCF
InChIKey: XHLLTWSYWBSEOC-IAGOWNOFSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Radioligand Binding Assay: The affinity of the compounds of the invention for cannabinoid CB1 receptors was determined using recommended amounts of membrane preparations (PerkinElmer) of human embryonic kidney (HEK) cells expressing the human CNR1 or CNR2 receptors in conjunction with 1.5 or 2.6 nM [3H]-CP-55,940 (Perkin Elmer) as radioligand, respectively. Binding was performed in binding buffer (50 mM Tris, 5 mM MgCl2, 2.5 mM EDTA, and 0.5% (wt/vol) fatty acid free BSA, pH 7.4 for CB1 receptor and 50 mM Tris, 5 mM MgCl2, 2.5 mM EGTA, and 0.1% (wt/vol) fatty acid free BSA, pH 7.4 for CB2 receptor) in a total volume of 0.2 ml for 1 h at 30Â° C. shaking. The reaction was terminated by rapid filtration through microfiltration plates coated with 0.5% polyethylenimine (UniFilter GFB filter plate; Packard). Bound radioactivity was analyzed for Ki using nonlinear regression analysis (Activity Base, ID Business Solution, Limited), with the Kd values for [3H]CP55,940 determined from saturation experiments. The compounds of formula (I) show an excellent affinity for the CB2 receptor.
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 481.57, ALogP 2.12, HBA 8, HBD 2, PSA 110.22, QED 0.31
Compound (SMILES): Cc1nnn(C)c1-c1cnc2c3ccc(C(C)(C)O)c(Cl)c3n([C@H](c3ccccc3)C3CCOCC3)c2c1
InChIKey: IWRRLINMFXHEBN-MUUNZHRXSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: All assay components were dissolved in buffer composition 20 mM Hepes pH 7.5, 150 mM NaCl, 5 mM DTT, 0.005% Tween 20, and 100 ug/ml BSA for BRD4 (1-477 and 44-460). The final concentrations of the bromodomain proteins are 1.6 nM BRD4(44-168), 1 nM BRD4(333-460), and 1 nM BRD4(1-477 or 44-460), and the fluorescent probe molecule is 100 nM, 50 nM, and 7.5 nM respectively. All proteins were biotinylated. A streptavidin labeled with terbium cryptate (Cisbio SA-Tb) was used as detection, and pre-mixed with the bromodomain protein at a final concentration of 0.2 nM. In some instances for BRD4 (44-460), anti-His terbium cryptate was used as a detection. 7.5 nl of dose-responsed test compound or dmso vehicle (0.0375%) was pre-spotted in a black Corning 384 well plate and 10 ul each of bromodomain/detection reagent and fluorescent small molecule solution were added to the plate, and the reaction incubated for 60 min at room temperature. Plates were then read on EnVision plate reader, (λex=340 nm, acceptor λEm=520 nm, and donor λEm=615 nm, LANCE D400 mirror). Time resolved fluorescence intensity measurements were made at both emissions, and the ratio of acceptor/donor was calculated and used for data analysis.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 530.07, ALogP 6.19, HBA 7, HBD 1, PSA 77.99, QED 0.29
Compound (SMILES): COc1cc(C(C)(C)O)cc2c1c1ncc(-c3c(C)nnn3C)cc1n2[C@H](c1ccccc1)C1CCOCC1
InChIKey: LLTWUQWCIITFCB-SSEXGKCCSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: All assay components were dissolved in buffer composition 20 mM Hepes pH 7.5, 150 mM NaCl, 5 mM DTT, 0.005% Tween 20, and 100 ug/ml BSA for BRD4 (1-477 and 44-460). The final concentrations of the bromodomain proteins are 1.6 nM BRD4(44-168), 1 nM BRD4(333-460), and 1 nM BRD4(1-477 or 44-460), and the fluorescent probe molecule is 100 nM, 50 nM, and 7.5 nM respectively. All proteins were biotinylated. A streptavidin labeled with terbium cryptate (Cisbio SA-Tb) was used as detection, and pre-mixed with the bromodomain protein at a final concentration of 0.2 nM. In some instances for BRD4 (44-460), anti-His terbium cryptate was used as a detection. 7.5 nl of dose-responsed test compound or dmso vehicle (0.0375%) was pre-spotted in a black Corning 384 well plate and 10 ul each of bromodomain/detection reagent and fluorescent small molecule solution were added to the plate, and the reaction incubated for 60 min at room temperature. Plates were then read on EnVision plate reader, (λex=340 nm, acceptor λEm=520 nm, and donor λEm=615 nm, LANCE D400 mirror). Time resolved fluorescence intensity measurements were made at both emissions, and the ratio of acceptor/donor was calculated and used for data analysis.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 525.65, ALogP 5.55, HBA 8, HBD 1, PSA 87.22, QED 0.31
Compound (SMILES): Cc1nnn(C)c1-c1cnc2c3cc(Cl)c(C(C)(C)O)cc3n([C@H](c3ccccc3)C3CCOCC3)c2c1
InChIKey: CEUZJDDUVBAUNK-GDLZYMKVSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: All assay components were dissolved in buffer composition 20 mM Hepes pH 7.5, 150 mM NaCl, 5 mM DTT, 0.005% Tween 20, and 100 ug/ml BSA for BRD4 (1-477 and 44-460). The final concentrations of the bromodomain proteins are 1.6 nM BRD4(44-168), 1 nM BRD4(333-460), and 1 nM BRD4(1-477 or 44-460), and the fluorescent probe molecule is 100 nM, 50 nM, and 7.5 nM respectively. All proteins were biotinylated. A streptavidin labeled with terbium cryptate (Cisbio SA-Tb) was used as detection, and pre-mixed with the bromodomain protein at a final concentration of 0.2 nM. In some instances for BRD4 (44-460), anti-His terbium cryptate was used as a detection. 7.5 nl of dose-responsed test compound or dmso vehicle (0.0375%) was pre-spotted in a black Corning 384 well plate and 10 ul each of bromodomain/detection reagent and fluorescent small molecule solution were added to the plate, and the reaction incubated for 60 min at room temperature. Plates were then read on EnVision plate reader, (λex=340 nm, acceptor λEm=520 nm, and donor λEm=615 nm, LANCE D400 mirror). Time resolved fluorescence intensity measurements were made at both emissions, and the ratio of acceptor/donor was calculated and used for data analysis.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 530.07, ALogP 6.19, HBA 7, HBD 1, PSA 77.99, QED 0.29
Compound (SMILES): COc1ccc(Cc2ccncc2)nc1-c1cccc([N+](=O)[O-])c1
InChIKey: XVLDVMKSXURTJL-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B1 S133D mutant by coupled enzyme based fluorescence analysis
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 321.34, ALogP 3.65, HBA 5, HBD 0, PSA 78.15, QED 0.53
Compound (SMILES): COc1ccc(/N=C(\N)CC(O)c2cc3c(F)cc(F)cc3c3cc(C(F)(F)F)ccc23)cc1
InChIKey: ZONAYHZJZVQMCT-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by fluorescence polarization assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 474.43, ALogP 6.41, HBA 3, HBD 2, PSA 67.84, QED 0.15
Compound (SMILES): COc1cc(C2CC(c3cccc(-n4cnnn4)c3)=NN2C(C)=O)cc(OC)c1OC
InChIKey: GOOKASPOKXCSJA-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 422.45, ALogP 2.39, HBA 9, HBD 0, PSA 103.96, QED 0.6
Compound (SMILES): COc1ccc(/C=C/C(=O)c2cc(I)c(Cl)cc2O)cc1
InChIKey: QLCWXMQTECDEPJ-QPJJXVBHSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin)
Measurement: IC50 = 11.72 nM (pChEMBL 7.929999828338623)
Descriptors: MW 414.63, ALogP 4.55, HBA 3, HBD 1, PSA 46.53, QED 0.45
Compound (SMILES): C/C(=N\OCc1cncc(C(=O)O)c1)c1ccc(OCc2c(-c3c(Cl)cccc3Cl)noc2C2CC2)cc1Cl
InChIKey: KQGFQANWFXEKQG-ROPCREHHSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR expressed in human Huh-7 cells co-transfected with FXRE-Luc reporter plasmid assessed as receptor transactivation incubated for 16 hrs by luciferase reporter gene assay
Measurement: EC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 586.86, ALogP 7.79, HBA 7, HBD 1, PSA 107.04, QED 0.15
Compound (SMILES): Cl.Oc1c(Cl)cc(Cl)c2ccc(/C=C/C3=CCN(Cc4ccccc4)CC3)nc12
InChIKey: MIFREJOCNRWKDE-UHDJGPCESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 2310 nM (pChEMBL 5.639999866485596)
Descriptors: MW 411.33, ALogP 6.09, HBA 3, HBD 1, PSA 36.36, QED 0.56
Compound (SMILES): CN1CCN(Cc2ccc(Nc3cc4ncn(-c5c(Cl)cccc5Cl)c(=O)c4cn3)cc2)CC1
InChIKey: HXHHYTUISPABOE-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of recombinant human Wee1 (214 to end residues) incubated for 1 hr in presence of tracer 178 by fluorescence based assay
Measurement: IC50 = 124 nM (pChEMBL 6.909999847412109)
Descriptors: MW 495.41, ALogP 4.58, HBA 7, HBD 1, PSA 66.29, QED 0.44
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(-c5ccccn5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: GLVMCPYFBLZASU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human N-terminal His6-tagged recombinant full-length PLK1 expressed in baculovirus infected Sf9 cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 537.63, ALogP 3.08, HBA 11, HBD 2, PSA 117.23, QED 0.34
Compound (SMILES): Cc1onc(-c2ccccc2)c1/C=C/CCCCCNC(=O)CS
InChIKey: IUTMTBXLLAOWGT-XYOKQWHBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human full length recombinant HDAC1 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 344.48, ALogP 4.27, HBA 4, HBD 2, PSA 55.13, QED 0.53
Compound (SMILES): O=C(Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1)c1ccccc1Cl
InChIKey: IZVBONMVWLTLNT-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat
Measurement: EC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 397.7, ALogP 4.9, HBA 2, HBD 2, PSA 49.33, QED 0.72
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(Nc3ccc(-c4nc5ccccc5[nH]4)cn3)cc2)cc1Br
InChIKey: CQYNUZHKKUSPDJ-UHFFFAOYSA-N
Target: Heparanase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y251
Assay: Inhibition of HPSE (unknown origin)
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 514.38, ALogP 6.39, HBA 5, HBD 3, PSA 91.93, QED 0.24
Compound (SMILES): COc1ccc2nc(-c3cn(Cc4ccc(C#N)cc4)nn3)sc2c1
InChIKey: FVILNASMBJRYQD-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Displacement of [11C]PBB3 in human brain tau incubated for 30 mins by radioligand binding assay
Measurement: Ki = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 347.4, ALogP 3.48, HBA 7, HBD 0, PSA 76.62, QED 0.56
Compound (SMILES): COc1ccc(-c2ccc3c(C4CCOC[C@@H]4C)nc(N4CCOC[C@@H]4C)nc3n2)cc1CO
InChIKey: QPPQETCVFWBCGA-NBJLRHFZSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin)
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 464.57, ALogP 3.56, HBA 8, HBD 1, PSA 89.83, QED 0.61
Compound (SMILES): CC(=O)N1N=C(c2nnn(-c3ccc(S(N)(=O)=O)cc3)c2C)CC1c1ccccc1
InChIKey: WHFLJRRDVMRTNB-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX-2 (unknown origin)
Measurement: IC50 = 2610 nM (pChEMBL 5.579999923706055)
Descriptors: MW 424.49, ALogP 1.92, HBA 7, HBD 1, PSA 123.54, QED 0.69
Compound (SMILES): CN1Cc2c(-c3ccc(CN(C)S(N)(=O)=O)cc3)ccnc2NC1=O.Cl
InChIKey: RBSTWYKPSHZPEM-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22413
Assay: Inhibition of ENPP1 (unknown origin)
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 361.43, ALogP 1.36, HBA 4, HBD 2, PSA 108.63, QED 0.86
Compound (SMILES): O=C(COc1ccc(Cl)cc1)Nc1nonc1NC(=O)COc1ccc(Cl)cc1
InChIKey: LFJYDFPHTVHUPV-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of SENP1 (unknown origin)
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 437.24, ALogP 3.41, HBA 7, HBD 2, PSA 115.58, QED 0.55
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc2c(ccn2-c2ccccc2)c1
InChIKey: KXMNTAAQVMYDJJ-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.37, ALogP 2.32, HBA 4, HBD 1, PSA 68.17, QED 0.81
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(C)c(C)c(C)c4)nn32)CC1
InChIKey: FLLXVDVLNOYACV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells using Biotin-AVLESEEELYSSARQ-NH2 as substrate preincubated for 1 hrs followed by substrate addition in presence of ATP at Km concentration and measured after 1 hrs by TR-FRET assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 421.55, ALogP 3.36, HBA 5, HBD 2, PSA 93.25, QED 0.74
Compound (SMILES): C=C(C)[C@H]1CC[C@]2(C)[C@H]3CC[C@@H]4[C@@]5(C)C[C@H](OC(C)=O)C[C@](C)(C(=O)O)[C@@H]5CC[C@@]4(C)[C@]3(C)CC[C@@H]12
InChIKey: PQTVRBKMGZAFGP-IRXNQVMWSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of recombinant HIV1 Protease using His-Lys-Ala-Arg-Val-Leu-(pNO2-Phe)-Glu-Ala-Nle-SerNH2 peptide as substrate
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 498.75, ALogP 7.66, HBA 3, HBD 1, PSA 63.6, QED 0.32
Compound (SMILES): O=C(NOCc1ccccc1)c1ccc2cccc(O)c2n1
InChIKey: KSFPRTGBGAXXIH-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacteria
UniProt: C7C422
Assay: Inhibition of C-terminal 6His-tagged full length NDM-1 (unknown origin) expressed in Escherichia coli BL21-DE3 using nitrocefin as substrate incubated for 15 mins followed by substrate addition by absorbance based microplate reader analysis
Measurement: IC50 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 294.31, ALogP 2.8, HBA 4, HBD 2, PSA 71.45, QED 0.73
Compound (SMILES): O=C(NCCc1ccccc1)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)NCCc4ccc5ccccc5c4)[C@H](C(=O)NCCc4ccc5ccccc5c4)C3)cc2)C[C@H]1C(=O)NCCc1ccc2ccccc2c1
InChIKey: WXGGDWQSQXLFNY-YBJJJAAASA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15399
Assay: Agonist activity at TLR2/TLR1 in human THP-1 cells
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 1011.24
Compound (SMILES): CC(=O)N1N=C2[C@H](C[C@H]3[C@@H]4CC[C@H]5C[C@@H](OC(=O)C(F)(F)F)CC[C@]5(C)[C@H]4CC[C@]23C)[C@H]1c1ccccc1
InChIKey: LFYHXQFDPXVULS-OUKVFGAQSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase (unknown origin)
Measurement: IC50 = 6576.58 nM (pChEMBL 5.179999828338623)
Descriptors: MW 530.63, ALogP 6.69, HBA 4, HBD 0, PSA 58.97, QED 0.4
Compound (SMILES): COC(=O)C[C@H]1[C@]2(C)C3=C(C)[C@H](c4ccoc4-c4ccc(C(=O)NCCCNC(=O)C[C@@H]5N=C(c6ccc(Cl)cc6)C6C(C)=C(C)SC6n6c(C)nnc65)cc4)C[C@H]3O[C@@H]2C2OC(=O)[C@]3(C)C=CC(=O)[C@@]1(C)[C@@H]23
InChIKey: SQFPHEMADDWFAY-NFGNGIJDSA-N
Target: E3 ubiquitin-protein ligase RNF114 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y508
Assay: Binding affinity to RNF114 (unknown origin)
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 1027.64
Compound (SMILES): COCCc1nc2c(N)nc3ccccc3c2n1CCCN(Cc1ccc(CC(=O)OC)cc1)C(=O)CN1CCN(C)CC1
InChIKey: JAFVJOPWLXIGNO-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 by reporter cell based assay
Measurement: EC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 601.75, ALogP 2.74, HBA 10, HBD 1, PSA 119.05, QED 0.23
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C4(Cl)CCCN(c5ccc(F)cc5)C4=O)cc3F)c2cc1OC
InChIKey: QXPVTEKDVMOBIP-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using poly(Glu-Tyr) at 4:1 ratio as substrate in presence of ATP incubated for 60 mins by ELISA
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 567.98, ALogP 6.07, HBA 6, HBD 1, PSA 89.99, QED 0.22
Compound (SMILES): CCCCCNc1nc(N)nc(C)c1Cc1cccc(CC(=O)OCC2CCN(C)CC2)c1
InChIKey: TZVVODMWZXRQIJ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 by reporter cell based assay
Measurement: EC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 453.63, ALogP 3.99, HBA 7, HBD 2, PSA 93.37, QED 0.39
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCCCN1CCN(Cc2ccccc2)CC1
InChIKey: DXQPJYSXJVUZSK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]SB269970 from human 5-HT7 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis
Measurement: Ki = 995 nM (pChEMBL 6)
Descriptors: MW 436.63, ALogP 3.84, HBA 5, HBD 0, PSA 39.15, QED 0.62
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)c1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](CN[C@H]1CSSC[C@@H](C(N)=O)NC1=O)CC1CCCCC1
InChIKey: LOWZTRVFKWGUFM-IGVINGPQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human kappa opioid receptor expressed in CHO-K1 cells incubated for 1 hr by 1450 microbeta scintillation counter analysis
Measurement: Ki = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 1002.28
Compound (SMILES): Cc1c(OCc2ccccc2)c(=O)ccn1-c1ccc(CC(=O)Nc2ccc(Cc3nc4ccccc4s3)cc2)cc1
InChIKey: YHAIWVRLIUGBMJ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 571.7, ALogP 7.11, HBA 6, HBD 1, PSA 73.22, QED 0.2
Compound (SMILES): Cc1c(-c2ccccc2)cccc1-c1nc2c(o1)CNCC2
InChIKey: LAVZXLHFQGGPKY-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 290.37, ALogP 3.96, HBA 3, HBD 1, PSA 38.06, QED 0.78
Compound (SMILES): CCNC(=O)C1=CC2C(c3cc(C(C)(C)O)ccc3Oc3c(C)cc(F)cc3C)=CN(C)C(=O)C2N1
InChIKey: KWRBIGNTVLPSMJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 BD1 (unknown origin) assessed as dissociation constant by ITC analysis
Measurement: Kd = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 493.58, ALogP 3.88, HBA 5, HBD 3, PSA 90.9, QED 0.57
Compound (SMILES): O=C(O)c1ccc2c(c1)Oc1ccc(OCc3c(-c4c(Cl)cc(F)cc4Cl)noc3C3CC3)nc1C1(CC1)C2
InChIKey: BPJBKCLBOFRAJG-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR (unknown origin) incubated for 15 mins by dual-luciferase reporter assay
Measurement: EC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 567.4, ALogP 7.72, HBA 6, HBD 1, PSA 94.68, QED 0.25
Compound (SMILES): CCOc1ccc(F)c(N2CC[C@@H](Oc3ccc(N4CC(C)(C)C[C@@H]4CC(=O)O)cc3)[C@H](C)C2)c1
InChIKey: HJSFLAWFGNKFEC-BNIKKZEQSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of PPARgamma (unknown origin)
Measurement: EC50 > 48000 nM (pChEMBL 4.318999767303467)
Descriptors: MW 484.61, ALogP 5.6, HBA 5, HBD 1, PSA 62.24, QED 0.53