lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nn3cc(-c4ccccc4)nc3s2)cc1
InChIKey: BVMZNBQRXKVSIF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human erythrocyte cytosolic carbonic anhydrase 1 by stopped-flow CO2 hydration assay
Measurement: Ki = 318 nM (pChEMBL 6.5)
Descriptors: MW 356.43, ALogP 2.77, HBA 6, HBD 1, PSA 90.35, QED 0.61
Compound (SMILES): Cc1cc(Nc2ncc(C#N)c(Nc3cccc(S(=O)(=O)NC(C)(C)C)c3)n2)ccc1N1CCN(C)CC1
InChIKey: BSPOXGNPEWSHFF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 using poly (Glu:Tyr) as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 534.69, ALogP 3.97, HBA 9, HBD 3, PSA 126.28, QED 0.41
Compound (SMILES): COc1ccc2c(n1)[nH]c1c3ccncc3cc(C#N)c21
InChIKey: RWAVDFHFFDMSHX-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 274.28, ALogP 3.14, HBA 4, HBD 1, PSA 74.59, QED 0.58
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)CC[C@@H]1NC(=O)[C@H]2CCCN2C(=O)[C@@H](N)CCCCNC(=O)CC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H]2CCCN2C(=O)[C@H](CCCCN)NC1=O)C(=O)O
InChIKey: JNJVJTIDEXTALQ-HSFNHRRSSA-N
Target: Neuropilin-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QWJ9
Assay: Inhibition of biotin labelled VEGF165 binding to rat recombinant NRP-1/Fc chimeric protein incubated for overnight by competitive ELISA method
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 1021.19
Compound (SMILES): c1ccc(-c2cc(OCCCCCN3CCN(c4ccccc4)CC3)ncn2)cc1
InChIKey: BZGQXSVFUPEENV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-HT from recombinant human 5-HT7A receptor expressed in CHOK1 cell membranes after 40 mins by liquid scintillation counting method
Measurement: Ki = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 402.54, ALogP 4.51, HBA 5, HBD 0, PSA 41.49, QED 0.49
Compound (SMILES): CN(C)CCN(C)c1ccc([N+](=O)[O-])cc1S(=O)(=O)N(C)/N=C/c1cnn2ccc(C#N)cc12
InChIKey: UZWYFVJGBGJHHK-OEAKJJBVSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of p110delta (unknown origin) using L-alpha phosphatidylinositol as substrate after 1 hr in presence of [gamma33]-ATP by thin layer chromatographic analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 484.54, ALogP 1.77, HBA 10, HBD 0, PSA 140.45, QED 0.25
Compound (SMILES): O=c1ccc(OCCCN2CCN(c3cccc(Cl)c3Cl)CC2)nn1-c1ccc(Cl)c(Cl)c1
InChIKey: KGGJBQKVVDZPQC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Displacement of [3H]8-OH-DPAT from 5-HT1A receptor in Sprague-Dawley rat cerebral cortex incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 624 nM (pChEMBL 6.210000038146973)
Descriptors: MW 528.27, ALogP 5.44, HBA 6, HBD 0, PSA 50.6, QED 0.38
Compound (SMILES): COc1ccc2c(c1)[nH]c1c3ccncc3cc(CN)c21
InChIKey: JIPWXCWXQYQCQS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 277.33, ALogP 3.34, HBA 3, HBD 2, PSA 63.93, QED 0.59
Compound (SMILES): O=C(O)CCCNCc1cc2c(-c3ccc4ccccc4c3)cccc2s1
InChIKey: ULLRYVBTGBAGLM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: Agonist activity at recombinant human S1PR4 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 = 211 nM (pChEMBL 6.679999828338623)
Descriptors: MW 375.49, ALogP 5.68, HBA 3, HBD 2, PSA 49.33, QED 0.41
Compound (SMILES): COc1ccc2[nH]cc(/C(C#N)=C/c3cnccc3C)c2c1
InChIKey: GBUPPMITCRSUBA-NTUHNPAUSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 289.34, ALogP 3.94, HBA 3, HBD 1, PSA 61.7, QED 0.74
Compound (SMILES): COc1ccc2[nH]cc(-c3cc4cnccc4cc3NC(C)=O)c2c1
InChIKey: ZNBZVAGNLWMGJD-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 331.38, ALogP 4.35, HBA 3, HBD 2, PSA 67.01, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nn3cc(-c4ccc(Br)cc4)nc3s2)cc1
InChIKey: VTVUDNDNNXPDFV-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human erythrocyte cytosolic carbonic anhydrase 1 by stopped-flow CO2 hydration assay
Measurement: Ki = 624 nM (pChEMBL 6.210000038146973)
Descriptors: MW 435.33, ALogP 3.53, HBA 6, HBD 1, PSA 90.35, QED 0.53
Compound (SMILES): CCC(=C(c1ccc(/C=C/C(=O)O)cc1)c1ccc(B(O)O)cc1)c1ccccc1
InChIKey: BINZFDGAOTWQNC-DBJGKHSESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluormone-labeled ES2 from recombinant full length human ERalpha ligand binding domain expressed in insect cells after 2 hrs by TR-FRET assay
Measurement: IC50 = 1.14 nM (pChEMBL 8.9399995803833)
Descriptors: MW 398.27
Compound (SMILES): O=C(C1=Cc2ccccc2OC1)N1CCC[C@H]1c1ncc(-c2ccccc2)[nH]1
InChIKey: TYTPXYLGTRLHNI-FQEVSTJZSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of rat lenses ALR2 using DL-glyceraldehyde as substrate preincubated for 10 mins followed by substrate addition measured for 4 mins
Measurement: IC50 = 3670 nM (pChEMBL 5.429999828338623)
Descriptors: MW 371.44, ALogP 4.22, HBA 3, HBD 1, PSA 58.22, QED 0.75
Compound (SMILES): FC(F)(F)c1c(OCc2ccccc2)ccn2c(CC3CC3)nnc12
InChIKey: RDNQZFSDTJMHLT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Positive allosteric modulation of human mGlu2 receptor expressed in HEK293 cells coexpressing rat glutamate transporter assessed as inhibition of forskolin-stimulated cAMP production measured after 30 mins in presence of orthosteric antagonist LY341495 by FLIPR assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 347.34, ALogP 4.28, HBA 4, HBD 0, PSA 39.42, QED 0.69
Compound (SMILES): COc1ccc2cc(-c3cccc4cc(CNCCCC(=O)O)sc34)ccc2c1
InChIKey: WWKMFVBIOIHLKZ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at recombinant human S1PR5 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 405.52, ALogP 5.68, HBA 4, HBD 2, PSA 58.56, QED 0.37
Compound (SMILES): COc1ccc2c(c1)[nH]c1c3ccncc3cc(CNC(C)=O)c21
InChIKey: RJJPKHZEICLSQD-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 319.36, ALogP 3.51, HBA 3, HBD 2, PSA 67.01, QED 0.61
Compound (SMILES): COc1ccc(C(=O)Nc2ccccc2-c2nnn(-c3ccc(SC)cc3)n2)cc1
InChIKey: LZLNMHPWWOLFIG-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of recombinant human GFP-fused ABCG2 expressed in MDCK2 cells assessed as reduction in pheophorbide A efflux preincubated for 30 mins followed by pheophorbide A addition measured after 2 hrs by flow cytometry
Measurement: IC50 = 251 nM (pChEMBL 6.599999904632568)
Descriptors: MW 417.49, ALogP 4.31, HBA 7, HBD 1, PSA 81.93, QED 0.47
Compound (SMILES): COc1ccc2c(c1)c(CC(=O)NCCCCCCC(=O)NO)c(C)n2C(=O)c1ccc(Cl)cc1
InChIKey: YVNZYSGUYVVTLL-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) after 24 hrs by SAMDI mass spectroscopic analysis
Measurement: IC50 = 854 nM (pChEMBL 6.070000171661377)
Descriptors: MW 500, ALogP 4.41, HBA 6, HBD 3, PSA 109.66, QED 0.21
Compound (SMILES): COc1ccc(S(=O)(=O)N(CCCCCNC(=O)CCCCC(=O)NCCNC(=O)CCN(CCNC(=O)OC(C)(C)C)CCC(=O)NCCNC(=O)CCCCC(=O)NCCCCCN([C@H](CO)C(=O)NO)S(=O)(=O)c2ccc(OC)cc2)[C@H](CO)C(=O)NO)cc1
InChIKey: YEVVFVQVGXPEQO-YYACYCFASA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 catalytic domain (112 to 445 residues) expressed in Escherichia coli assessed as inhibition of hydrolysis of Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by fluorimetric assay
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 1359.63
Compound (SMILES): Cc1ccc(C(=O)NN=C2CC(c3ccccc3)NC(c3ccccc3)C2)cc1
InChIKey: RTTQSGJLKJCOQE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase by Ellman's method
Measurement: IC50 = 50100 nM (pChEMBL 4.300000190734863)
Descriptors: MW 383.5, ALogP 4.95, HBA 3, HBD 2, PSA 53.49, QED 0.63
Compound (SMILES): FC(F)(F)c1c(OC[C@H]2C[C@@H]2c2ccc(Cl)cc2)ccn2c(CC3CC3)nnc12
InChIKey: LETPPZNSGLCXSE-GDBMZVCRSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Positive allosteric modulation of human mGlu3 receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 30 mins in presence of orthosteric antagonist LY341495 by FLIPR assay
Measurement: EC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 421.85, ALogP 5.54, HBA 4, HBD 0, PSA 39.42, QED 0.52
Compound (SMILES): CN(Cc1ccccn1)c1ccc([N+](=O)[O-])cc1S(=O)(=O)N(C)/N=C/c1cnn2ccc(C#N)cc12
InChIKey: JXBONZLAZJXGLS-VULFUBBASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of p110delta (unknown origin) using L-alpha phosphatidylinositol as substrate after 1 hr in presence of [gamma33]-ATP by thin layer chromatographic analysis
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 504.53, ALogP 2.8, HBA 10, HBD 0, PSA 150.1, QED 0.2
Compound (SMILES): Cc1nc2ccccc2c(=O)n1CCCCCN1CCN(c2ccccc2)CC1
InChIKey: BNZKPNIFDGLVFS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from recombinant human 5-HT1A receptor expressed in CHOK1 cell membranes after 1 hr by liquid scintillation counting method
Measurement: Ki = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 390.53, ALogP 3.7, HBA 5, HBD 0, PSA 41.37, QED 0.58
Compound (SMILES): COc1cccc2c1OCC(C(=O)NCc1ncc(-c3ccccc3)[nH]1)=C2
InChIKey: WGKKIBZUIUUWLC-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of rat lenses ALR2 using DL-glyceraldehyde as substrate preincubated for 10 mins followed by substrate addition measured for 4 mins
Measurement: IC50 = 731 nM (pChEMBL 6.139999866485596)
Descriptors: MW 361.4, ALogP 3.18, HBA 4, HBD 2, PSA 76.24, QED 0.73
Compound (SMILES): COc1cccc2c1OCC(C(=O)N1CCC[C@H]1c1ncc(-c3cccnc3)[nH]1)=C2
InChIKey: UBWKOQNKFNAMHD-IBGZPJMESA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of rat lenses ALR2 using DL-glyceraldehyde as substrate preincubated for 10 mins followed by substrate addition measured for 4 mins
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 402.45, ALogP 3.62, HBA 5, HBD 1, PSA 80.34, QED 0.72
Compound (SMILES): Cc1ccccc1-c1cccc2cc(CNCCCC(=O)O)sc12
InChIKey: FAQQWLOPBMREGY-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at recombinant human S1PR5 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 = 3540 nM (pChEMBL 5.449999809265137)
Descriptors: MW 339.46, ALogP 4.83, HBA 3, HBD 2, PSA 49.33, QED 0.61
Compound (SMILES): CCCC(C)COc1ccc([C@@H](NC(=O)[C@@H](C)c2ccccc2)C(=O)N(C)C)cc1
InChIKey: MUTBEIGKAHNCFX-HXCXSPQYSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at PPLS-HA-tagged-GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP production measured after 30 mins by TR-FRET assay
Measurement: EC50 = 616 nM (pChEMBL 6.210000038146973)
Descriptors: MW 410.56, ALogP 4.55, HBA 3, HBD 1, PSA 58.64, QED 0.63
Compound (SMILES): CCc1ccccc1-c1cccc2cc(CNc3cccc(CC(=O)O)c3)sc12
InChIKey: DQEIXFLEOVOQHX-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at recombinant human S1PR5 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 = 3970 nM (pChEMBL 5.400000095367432)
Descriptors: MW 401.53, ALogP 6.37, HBA 3, HBD 2, PSA 49.33, QED 0.38
Compound (SMILES): CC(C)(C)[C@]1(O)CCN2C[C@@H]3c4ccccc4CCc4cccc(c43)[C@@H]2C1
InChIKey: ZZJYIKPMDIWRSN-SLSDLSHTSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]methyl-spiperone from human recombinant dopamine D3 receptor expressed in CHO cells measured after 60 mins by scintillation counting method
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 361.53, ALogP 4.84, HBA 2, HBD 1, PSA 23.47, QED 0.73
Compound (SMILES): C=CC(=O)Oc1ccccc1Nc1nc(Nc2cccc(N3CCN(C(C)=O)CC3)c2)ncc1Cl
InChIKey: MENPTCWEPFMOHL-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Inhibition of full length recombinant human His-tagged MEK1 expressed in baculovirus expression system after 1 hr by TR-FRET based LanthaScreen assay
Measurement: IC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 492.97, ALogP 4.38, HBA 8, HBD 2, PSA 99.69, QED 0.28
Compound (SMILES): COc1cccc2c1[nH]c1c3ccncc3cc(C#N)c21
InChIKey: UHOPJKMQVDXYAV-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 273.3, ALogP 3.75, HBA 3, HBD 1, PSA 61.7, QED 0.57
Compound (SMILES): CCN(CC)C(=O)Oc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1
InChIKey: YKEKEEWUAKLXGN-NTEUORMPSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected High 5 insect cells using kynuramine as substrate incubated for 30 mins by spectrofluorometric method
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 382.46, ALogP 4.19, HBA 5, HBD 1, PSA 70.08, QED 0.57
Compound (SMILES): CCCC(C)COc1ccc([C@@H](NC(=O)Cc2ccccc2F)C(=O)OC)cc1
InChIKey: QNKCEDCTEODDMZ-VXNXSFHZSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at PPLS-HA-tagged-GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP production measured after 30 mins by TR-FRET assay
Measurement: EC50 = 7870 nM (pChEMBL 5.099999904632568)
Descriptors: MW 401.48, ALogP 4.21, HBA 4, HBD 1, PSA 64.63, QED 0.61
Compound (SMILES): COc1cc([C@H]2[C@H](c3ccccc3)C(=O)N2c2ccc(S(N)(=O)=O)cc2)cc(OC)c1OC
InChIKey: XHNZYDLNBBLDGC-VXKWHMMOSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase-2 using CO2 as substrate preincubated for 10 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 468.53, ALogP 3.23, HBA 6, HBD 1, PSA 108.16, QED 0.53
Compound (SMILES): O=S(=O)(c1ccccc1)n1ccc2c(N3CCN(CCNCc4ccccc4)CC3)cccc21
InChIKey: RMGARRVNUBPKJI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE preincubated for 5 mins followed by butyrylthiocholine iodide substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 1307 nM (pChEMBL 5.880000114440918)
Descriptors: MW 474.63, ALogP 3.79, HBA 6, HBD 1, PSA 57.58, QED 0.39
Compound (SMILES): COc1ccc(C(=O)Nc2ccccc2-c2nnn(-c3ccc(OC)cc3)n2)cc1
InChIKey: SXABNFMIJZBSPG-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 in human H460/MX20 cells assessed as potentiation of mitoxantrone induced antiproliferative activity by measuring mitoxantrone IC50 at 3 uM preincubated for 2 hrs followed by mitoxantrone addition measured after 72 hrs by MTT assay (Rvb = 6.161 +/- 0.172 microM)
Measurement: IC50 = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 401.43, ALogP 3.6, HBA 7, HBD 1, PSA 91.16, QED 0.53
Compound (SMILES): C/C(=N\N(C)S(=O)(=O)c1cc([N+](=O)[O-])ccc1N(C)CCN(C)C)c1cnn2ccc(C#N)cc12
InChIKey: SJIXEBMUNVXCHL-PCLIKHOPSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of p110delta (unknown origin) using L-alpha phosphatidylinositol as substrate after 1 hr in presence of [gamma33]-ATP by thin layer chromatographic analysis
Measurement: IC50 = 658 nM (pChEMBL 6.179999828338623)
Descriptors: MW 498.57, ALogP 2.16, HBA 10, HBD 0, PSA 140.45, QED 0.25
Compound (SMILES): O=C(O)CNCc1cc2cc(-c3ccc4ccccc4c3)ccc2s1
InChIKey: MBDKAWXFKIFHBK-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: Agonist activity at recombinant human S1PR4 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 347.44, ALogP 4.9, HBA 3, HBD 2, PSA 49.33, QED 0.54
Compound (SMILES): O=c1ccc(OCCCN2CCC(c3noc4cc(F)ccc34)CC2)nn1-c1cccc(Cl)c1Cl
InChIKey: MJNIHQSWWWZHAP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Displacement of [3H]8-OH-DPAT from 5-HT1A receptor in Sprague-Dawley rat cerebral cortex incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 517.39, ALogP 5.47, HBA 7, HBD 0, PSA 73.39, QED 0.3
Compound (SMILES): N#Cc1cc2ccccn2c2nc3ccccc3c1-2
InChIKey: KTYYOPKGRHNARA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-tagged human recombinant DYRK1A expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 243.27, ALogP 3.46, HBA 3, HBD 0, PSA 41.09, QED 0.47
Compound (SMILES): CC1(C)C(=O)Nc2nc(Nc3ccccc3)ncc21
InChIKey: PZRUBYAEITWWDH-UHFFFAOYSA-N
Target: MAP/microtubule affinity-regulating kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96L34
Assay: Inhibition of human MARK4 expressed in HEK293T cells coexpressing tau protein assessed as reduction in tau phosphorylation at Ser262 residues by AlphaLisa assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 254.29, ALogP 2.45, HBA 4, HBD 2, PSA 66.91, QED 0.86
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nc3scc(-c4ccccc4)n3n2)cc1
InChIKey: DIDHBTZRTBRKQW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human erythrocyte cytosolic carbonic anhydrase 2 by stopped-flow CO2 hydration assay
Measurement: Ki = 18.1 nM (pChEMBL 7.739999771118164)
Descriptors: MW 356.43, ALogP 2.77, HBA 6, HBD 1, PSA 90.35, QED 0.61
Compound (SMILES): CCCC(C)COc1ccc([C@@H](NC(=O)Cc2cccc(F)c2)C(=O)OC)cc1
InChIKey: UXYYWGJVRZWIQM-VXNXSFHZSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at PPLS-HA-tagged-GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP production measured after 30 mins by TR-FRET assay
Measurement: EC50 = 3910 nM (pChEMBL 5.409999847412109)
Descriptors: MW 401.48, ALogP 4.21, HBA 4, HBD 1, PSA 64.63, QED 0.61
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(=O)(=O)NCCCCCCC(=O)NO)cc2)cc1
InChIKey: VLMFJLCDTHAPTK-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) after 24 hrs by SAMDI mass spectroscopic analysis
Measurement: IC50 = 4050 nM (pChEMBL 5.389999866485596)
Descriptors: MW 524.57, ALogP 4.6, HBA 6, HBD 3, PSA 113.32, QED 0.19
Compound (SMILES): CCc1ccccc1-c1cccc2cc(CNCCCC(=O)O)sc12
InChIKey: SSFAGLSGBSHBQL-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at recombinant human S1PR5 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 353.49, ALogP 5.09, HBA 3, HBD 2, PSA 49.33, QED 0.55
Compound (SMILES): COc1cc(O)ccc1-c1ccc2c(-c3nc4ccc(N5CCN(C)CC5)cc4[nH]3)n[nH]c2c1
InChIKey: XVARKOKUVCKXQW-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK4/cyclin D3 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 454.53, ALogP 4.24, HBA 6, HBD 3, PSA 93.3, QED 0.38
Compound (SMILES): Cc1cccc(Cc2n[nH]c3cc(O)c(C(=O)N(C)c4ccc(N5CCN(C)CC5)cc4)cc23)c1
InChIKey: VPANYTMTTIRHCW-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Recombinant Hsp90 [His-Tev-huHsp90-alpha (9-236)] was immobilized on a Biacore CM5 chip at 25 degrees C and a flow rate of 30 uL/min using amine coupling at pH 4.50 according to Biacore standard protocol. Hsp90 was applied at a concentration of 20 ug/mL with 50uM 17-DMAG.Data sets were processed and analyzed using the software Biacore 4000 Evaluation. Solvent corrected and double-referenced association and dissociation phase data were fitted to a simple 1:1 interaction model with mass transport limitations
Measurement: Kd = 3.567 nM (pChEMBL 8.449999809265137)
Descriptors: MW 469.59, ALogP 4.2, HBA 5, HBD 2, PSA 75.7, QED 0.46
Compound (SMILES): CCOc1cc(=O)n(C)cc1-c1cc(NC(=O)Nc2cccc(OC)c2)ccc1Oc1ccc(F)cc1F
InChIKey: STGMAEYWPTWYRF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Assay method B: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution from one of the following: 0.47 mM to 7.8 nM. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus# 6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe. The final concentration of 1X assay mixture for assay methods A, B and C contains 2% DMSO, 8 nM His-tagged bromodomain, 1 nM Europium-conjugated anti-His-tag antibody and 100 nM or 30 nM probe (for BDI or BDII, respectively) and compound concentration in the range of: 49.02 μM-15.63 nM for method A, 9.19 μM 150 pM for method B, and 0.92 μM 15 pM for method C. After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki > 4080 nM (pChEMBL 5.388999938964844)
Descriptors: MW 521.52, ALogP 6.17, HBA 6, HBD 2, PSA 90.82, QED 0.29
Compound (SMILES): COCC[C@H]1C[C@@H]1c1cncc(N2CCCN(C)CC2)c1
InChIKey: PGQPCQRMIKUJAS-YOEHRIQHSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Displacement of [3H]epibatidine from rat alpha3beta2 nAChR by liquid scintillation counting
Measurement: Ki = 681 nM (pChEMBL 6.170000076293945)
Descriptors: MW 289.42, ALogP 2.36, HBA 4, HBD 0, PSA 28.6, QED 0.83
Compound (SMILES): CNCCN1CCC(Oc2ccccc2)CC1
InChIKey: ZYQFUTZIWVTGCH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 234.34, ALogP 1.75, HBA 3, HBD 1, PSA 24.5, QED 0.84
Compound (SMILES): CCOCc1c(-c2cc3cc(C)cc(OC)c3s2)c2c(N)ncnn2c1C(C)O
InChIKey: RYXCQMCDTUCUJT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Kinase Assay: For the assay, 50 nl of each stock solution of the test compound in DMSO was pipetted into a black, low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany) 2 ul of a solution of the above FGFR-3 fusion protein in aqueous assay buffer [8 mM MOPS pH 7.0, 10 mM magnesium acetate, 1.0 mM dithiothreitol, 0.05% (w/v) bovine serum albumin (BSA), 0.07% (v/v) Tween-20, 0.2 mM EDTA] was added, and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compound to the enzyme. Then, the kinase reaction was started by the addition of 3 ul of a solution of adenosine triphosphate (ATP, 16.7 uM; final concentration in the 5 ul assay volume=10 uM) and substrate (0.8 uM; final concentration in the 5 ul assay volume=0.5 uM) in assay buffer, and the resulting mixture was incubated for a reaction time of 60 min at 22° C. The concentration of FGFR-3 fusion protein was adjusted depending on the activity of the enzyme lot.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 412.52, ALogP 4.1, HBA 8, HBD 2, PSA 94.9, QED 0.5
Compound (SMILES): O=C(CCC1CCOCC1)N1CCC2(CC1)CC2CNC(=O)N1Cc2ccncc2C1
InChIKey: GDZBTZPHHNUXKZ-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 426.56, ALogP 2.94, HBA 4, HBD 1, PSA 74.77, QED 0.79
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(O)CO)c4)nc3c2)c1
InChIKey: FDEHCJCKFIQBIS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.55, ALogP 3.41, HBA 9, HBD 2, PSA 105.76, QED 0.36
Compound (SMILES): Cn1cnc2cc(OCC(=O)NCC(O)CN3CCc4ccccc4C3)ccc21
InChIKey: XYDOBRWXUORDKH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 in human Z138 cells assessed as decrease in di-methyl arginine levels after 96 hrs by Western blot method
Measurement: EC50 = 101 nM (pChEMBL 7)
Descriptors: MW 394.48, ALogP 1.49, HBA 6, HBD 2, PSA 79.62, QED 0.63
Compound (SMILES): C=CC(=O)Nc1cc(N2CCN(CC)CC2)ccc1Nc1cc(N(C)C(=O)Nc2c(Cl)cccc2Cl)ncn1
InChIKey: AIQLASADOJQUSY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Kinase HotSpotâ¿¢ Assay: Compounds were profiled for FGFR inhibition activity at Reaction Biology Corporation (Malvern, Pa.) with their Kinase HotSpot assay. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.Recombinant FGFR1 (2.5 nM), FGFR2 (1 nM), FGFR3 (5 nM), or FGFR4 (12 nM) (Invitrogen) was prepared as a mixture with substrate KKKSPGEYVNIEFG (SEQ ID NO:1) (20 uM, FGFR1 substrate); and Poly [E,Y]4:1 (0.2 mg/ml, FGFR2,3,4 substrate)] in kinase reaction buffer (20 mM HEPES-HCl, pH 7.5, 10 mM MgCl2, 2 mM MnCl2, 1 mM EGTA, 0.02% Brij35, 0.1 mM Na3VO4, 0.02 mg/ml BSA, 2 mM DTT, and 1% DMSO). Compound was added to the enzyme/substrate mixture using acoustic technology (Labcyte Echo 550, Sunnyvale, Calif.) (see, Olechno et al., 2006, Improving IC50 results with acoustic droplet ejection. JALA 11, 240-246) and pre-incubated for 0, 15, or 60 minutes at room temperature. After compound pre-incubation, a mixture of ATP (Sigma-Aldrich) and 33P-γ-ATP (PerkinElmer) was added to a final concentration of 10 uM to initiate kinase reactions. Reactions were incubated for 120 minutes at room temperature and then spotted onto Whatman P81 ion exchange filter paper. Unbound phosphate was removed by extensively washing filters in 0.75% phosphoric acid. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 569.5, ALogP 5.46, HBA 7, HBD 3, PSA 105.73, QED 0.31
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc2ccccc12
InChIKey: YYPFVEUHFBKVDE-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64373
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki = 88.01 nM (pChEMBL 7.050000190734863)
Descriptors: MW 846.41, ALogP 9.14, HBA 10, HBD 2, PSA 143.35, QED 0.09
Compound (SMILES): O=C(O)c1ccc(-c2ccccc2Cl)cc1Cn1nc(-c2ccc(Cl)cc2)n(CC(O)C(F)(F)F)c1=O
InChIKey: YDSYCVMDWHVXLQ-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Cellular In Vitro Assay: On the day before the assay, the cells are plated out in culture medium (DMEM, 10% FCS, 2 mM glutamine, 10 mM HEPES) in 384-well microtiter plates and kept in a cell incubator (96% humidity, 5% v/v CO2, 37° C.). On the day of the assay, the culture medium is replaced by a Tyrode solution (140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 2 mM CaCl2, 20 mM glucose, 20 mM HEPES), which additionally contains the cofactor coelenterazine (50 μM), and the microtiter plate is then incubated for a further 3-4 hours. The test substances in various concentrations are placed for 10 to 20 minutes in the wells of the microtiter plate before the agonist [Arg8]-vasopressin is added, and the resulting light signal is measured immediately in the luminometer.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 552.34, ALogP 5.36, HBA 6, HBD 2, PSA 97.35, QED 0.32
Compound (SMILES): CC(C(N)=O)N(C)c1ncc(-c2ccnc(Nc3ccc(CN4CCOCC4)nc3)n2)cc1C#N
InChIKey: HTEWKSAPNYLCKR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Time-Resolved Fluorescence-based Lanthascreen Assay: Kinase inhibition assays (10 μL) were performed at 20° C. in 384-well plate format. Compound IC50 values were determined at the apparent Km for ATP (20 μM) based on a radiometric assay (Invitrogen) using 8 or 10 point curves in duplicate. The final reaction conditions contained 400 nM fluorescein-IkBα substrate (DRHDSGLDSMKDE), 20 μM ATP, 2 nM or 8 nM IKKε or TBK1 kinase respectively, and 3% DMSO in kinase assay buffer consisting of 50 mM HEPES (pH 7.5), 10 mM MgCl, 1 mM EGTA, 0.01% Brij-35.Compound dilutions were prepared from 10 mM DMSO stocks by dilution into DMSO. Compound dilution series were further diluted in kinase assay buffer to give a 12% DMSO stock, the final concentration in the assay being 3% DMSO.The kinase phosphorylation assay was initiated by the addition of the kinase and the reaction was allowed to proceed for 1 h or 2.5 h for IKKε and TBK-1 kinase respectively.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 473.54, ALogP 1.69, HBA 10, HBD 2, PSA 146.18, QED 0.5
Compound (SMILES): CS(=O)(=O)NC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)COc2ccccc2)[C@H](O)C[C@@H]1O
InChIKey: HOLXELUFBALNSM-CNAXQHPCSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay
Measurement: EC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 467.58, ALogP 1.53, HBA 7, HBD 4, PSA 133.16, QED 0.27
Compound (SMILES): COc1ccccc1N1CCC(CC#N)(n2cc(C(N)=O)c(Nc3ccc(F)cc3)n2)CC1
InChIKey: QYICUDHXNVEGCM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 448.5, ALogP 3.78, HBA 7, HBD 2, PSA 109.2, QED 0.57
Compound (SMILES): COc1ccc(C[C@@H]2NC(=O)C3(CCCC3)NC(=O)[C@H](CC(C)C)NCCOc3ccccc3/C=C\CNC2=O)cc1
InChIKey: ZZFOXDJZECXZJH-HHTQCXTOSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GSHR1a transfected in CHOK1 cells co-expressing Galpha16 assessed as increase in Ca2+ release by aequorin assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 576.74, ALogP 3.38, HBA 6, HBD 4, PSA 117.79, QED 0.43
Compound (SMILES): COc1ccc(CN2CCC(CC#N)(n3cc(C(N)=O)c(Nc4ccnc(F)c4)n3)CC2)cc1
InChIKey: JPLAAUREDHYGGU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 463.52, ALogP 3.17, HBA 8, HBD 2, PSA 122.09, QED 0.49
Compound (SMILES): N#CCC1(n2cc(C(N)=O)c(Nc3ccc(F)cc3)n2)CCN(c2cccc(C#N)n2)CC1
InChIKey: HEGGZZRYOMYSMQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 444.47, ALogP 3.04, HBA 8, HBD 2, PSA 136.65, QED 0.6
Compound (SMILES): C=CC(=O)Nc1cc(CN2CCN(CC)CC2)ccc1Nc1cc(N(C)C(=O)Nc2c(Cl)c(OC)cc(OC)c2Cl)ncn1
InChIKey: QJVYXBFCQZNMFJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Kinase HotSpotâ¿¢ Assay: Compounds were profiled for FGFR inhibition activity at Reaction Biology Corporation (Malvern, Pa.) with their Kinase HotSpot assay. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.Recombinant FGFR1 (2.5 nM), FGFR2 (1 nM), FGFR3 (5 nM), or FGFR4 (12 nM) (Invitrogen) was prepared as a mixture with substrate KKKSPGEYVNIEFG (SEQ ID NO:1) (20 uM, FGFR1 substrate); and Poly [E,Y]4:1 (0.2 mg/ml, FGFR2,3,4 substrate)] in kinase reaction buffer (20 mM HEPES-HCl, pH 7.5, 10 mM MgCl2, 2 mM MnCl2, 1 mM EGTA, 0.02% Brij35, 0.1 mM Na3VO4, 0.02 mg/ml BSA, 2 mM DTT, and 1% DMSO). Compound was added to the enzyme/substrate mixture using acoustic technology (Labcyte Echo 550, Sunnyvale, Calif.) (see, Olechno et al., 2006, Improving IC50 results with acoustic droplet ejection. JALA 11, 240-246) and pre-incubated for 0, 15, or 60 minutes at room temperature. After compound pre-incubation, a mixture of ATP (Sigma-Aldrich) and 33P-γ-ATP (PerkinElmer) was added to a final concentration of 10 uM to initiate kinase reactions. Reactions were incubated for 120 minutes at room temperature and then spotted onto Whatman P81 ion exchange filter paper. Unbound phosphate was removed by extensively washing filters in 0.75% phosphoric acid. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.
Measurement: IC50 = 2027 nM (pChEMBL 5.690000057220459)
Descriptors: MW 643.58, ALogP 5.47, HBA 9, HBD 3, PSA 124.19, QED 0.23
Compound (SMILES): O=C(NCCc1c[nH]c2ccccc12)c1cc2ccc(OCc3ccc(F)cc3)cc2oc1=O
InChIKey: VWTKPEFXBYNDFD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate measured for 2 mins by Ellman's method
Measurement: IC50 = 29700 nM (pChEMBL 4.53000020980835)
Descriptors: MW 456.47, ALogP 4.96, HBA 4, HBD 2, PSA 84.33, QED 0.34
Compound (SMILES): O=C(CN1CCC2(CC1)Cc1cc(F)ccc1C2=O)N(Cc1nc2c(c(=O)[nH]1)COCC2)CC1CC1
InChIKey: UHPJRQMZYNOZHL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Biochemical Assay: The autoparsylation activity of the TNKS 1/2 or PARP1/2 enzymes was measured by the liquid chromatography-mass spectrometry (LC/MS) detection of nicotinamide as readout. Compound activity in inhibiting the TNKS and PARP autoparsylation was evaluated by IC50 measurements. In the compound screening assays, the reaction is composed of 5 μL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 μM, 20 nM of purified enzyme, and 250 μM of β-NAD+ in the 1× Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 μL of 5× quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 μL of the 5× quenching solution per well was added prior to the addition of β-NAD+.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 494.57, ALogP 2.24, HBA 6, HBD 1, PSA 95.6, QED 0.66
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)Cn1c(=O)n(C2CCN(C(=O)CN3CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC3)CC2)c2ccccc21)C(C)C)C(N)=O
InChIKey: QSSQSALZTGEXBT-ARTAVBMCSA-N
Target: Neuromedin-B receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P24053
Assay: Displacement of [125I]-NMB from NMB receptor in rat C6 cells
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 1583.84
Compound (SMILES): COc1cccc(OC)c1C1CC(C)C(=O)N1Cc1ccc(OC(F)F)cc1
InChIKey: OPDJWYZBEUMZKV-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: In Vitro Assay: Intracellular Calcium Measurements : In Vitro Assay: Intracellular Calcium Measurements:Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 g/ml G418, 100 U/ml penicillin, 100 g/ml streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37° C. in 5% CO2. Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH:water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES for use in the assay at a final concentration of 3 nM.Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES. On the day of the assay, 50 μl of staining buffer (HBSS containing 1% FCS, 20 mM HEPES, NaHCO3: 0.375 g/l, 5 mM probenecid (Sigma) and 3 M of the fluorescent calcium indicator fluo-4 AM (1 mM stock solution in DMSO, containing 10% pluronic) is added to each well. The 384-well cell-plates are incubated for 50 min at 37° C. in 5% CO2 followed by equilibration at RT for 30 min before measurement.
Measurement: IC50 = 621 nM (pChEMBL 6.210000038146973)
Descriptors: MW 391.41, ALogP 4.41, HBA 4, HBD 0, PSA 48, QED 0.7
Compound (SMILES): CNS1(O)C[C@@](C)(c2cc(NC(=O)c3ccc(OC)cn3)ccc2F)NC(=N)N1C
InChIKey: VZNMUSBVXSORSX-IBGZPJMESA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: HTRF FRET Assay: This assay monitors the increase of 620 nm fluorescence that resulted from BACE1 cleavage of an APPswedish APPswe mutant peptide FRET substrate (QSY7-EISEVNLDAEFC-Europium-amide). This substrate contains an N-terminal QSY7 moiety that serves as a quencher of the C-terminal Europium fluorophore (620 nm Em). In the absence of enzyme activity, 620 nm fluorescence is low in the assay and increased linearly over 3 hours in the presence of uninhibited BACE1 enzyme Inhibition of BACE1 cleavage of the QSY7-APPswe-Eu substrate by inhibitors is manifested as a suppression of 620 nm fluorescence. Varying concentrations of inhibitors at 3× the final desired concentration in a volume of 10 μl are preincubated with purified human BACE1 catalytic domain (3 nM in 10 μl) for 30 minutes at 30° C. in reaction buffer containing 20 mM Na-Acetate pH 5.0, 10% glycerol, 0.1% Brij-35 and 7.5% DSMO. Reactions are initiated by addition of 10 μl of 600 nM QSY7-APPswe-Eu substrate (200 nM final) to give a final reaction volume of 30 μl in a 384 well Nunc HTRF plate. The reactions are incubated at 30° C. for 1.5 hours. The 620 nm fluorescence is then read on a Rubystar HTRF plate reader (BMG Labtechnologies) using a 50 millisecond delay followed by a 400 millisecond acquisition time window Inhibitor.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 436.51, ALogP 2.49, HBA 6, HBD 5, PSA 122.6, QED 0.49