lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Oc1ccc2[nH]c(-c3ccccc3)nc2c1CN1CCCCC1
InChIKey: FVHKIGHCUWTXCC-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 307.4, ALogP 3.92, HBA 3, HBD 2, PSA 52.15, QED 0.77
Compound (SMILES): Cc1cc2c(-c3ccc[nH]c3=O)c(C(=O)NS(=O)(=O)C3CC3)n(Cc3cc(F)ccc3F)c2cc1F
InChIKey: GXKRHWPFLHJAKI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 preincubated prior to substrate addition
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 515.51, ALogP 3.99, HBA 5, HBD 2, PSA 101.03, QED 0.41
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin)-mediated mitoxantrone efflux expressed in HEK293 cells after 30 mins by flow cytometric analysis
Measurement: EC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): O=C(Cc1ccc(Cc2ccccc2)cc1)OC[C@H]1CO1
InChIKey: AADKPDGTJHDJAJ-QGZVFWFLSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Non-competitive inhibition of human recombinant MAGL assessed as 7-hydroxycoumarin level using umbelliferyl arachidonate as substrate by luminescence spectrophotometer
Measurement: Ki = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 282.34, ALogP 2.76, HBA 3, HBD 0, PSA 38.83, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(O)c(C(=O)Nc2ccc(CN)cc2)c1
InChIKey: SVSGGNNTSJRRTJ-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Activities on Plasmin (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 14400 nM (pChEMBL 4.840000152587891)
Descriptors: MW 298.39, ALogP 3.4, HBA 3, HBD 3, PSA 75.35, QED 0.81
Compound (SMILES): Nc1ncnc(Nc2ccc(Oc3ccc(Cl)cc3)cc2)n1
InChIKey: JSPXITPXMRLRIW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of dofetilide from human ERG
Measurement: Ki = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 313.75, ALogP 3.64, HBA 6, HBD 2, PSA 85.95, QED 0.76
Compound (SMILES): Nc1cncc(Nc2ccc(Oc3ccc(OC(F)(F)F)cc3)cc2)n1
InChIKey: YBPKUYHMTYRITD-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by PatchXpress voltage patch clamp assay
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 362.31, ALogP 4.49, HBA 6, HBD 2, PSA 82.29, QED 0.7
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: MAP kinase-activated protein kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IW41
Assay: Inhibition of MK5 by TR-FRET based LanthaScreen assay
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells by qPCR assay
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]lysergic from human 5-HT2BR expressed in HEK cell membranes incubated in dark for 90 mins by microbeta scintillation counting method
Measurement: Ki = 675 nM (pChEMBL 6.170000076293945)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCc1n[nH]c2ncnc(N3CCN(c4cc(Cl)cc(NCCN(C)C)c4C)CC3)c12
InChIKey: ACXREQVXILYMKB-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1-mediated GSK3beta phosphorylation in human PC3 cells after 3 hrs by chemiluminescence assay
Measurement: IC50 = 9026 nM (pChEMBL 5.039999961853027)
Descriptors: MW 443, ALogP 3.18, HBA 7, HBD 2, PSA 76.21, QED 0.58
Compound (SMILES): Cc1c(NCCN(C)C)cc(Cl)cc1N1CCN(c2ncnc3[nH]nc(Br)c23)CC1
InChIKey: GPNUVUGMFDKAJH-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23443
Assay: Inhibition of p70S6K-mediated ribosomal protein S6 phosphorylation in human PC3 cells after 3 hrs by chemiluminescence assay
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 493.84, ALogP 3.38, HBA 7, HBD 2, PSA 76.21, QED 0.55
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)N(C)C(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: AAMHUKDMAMABLC-UAGACBDMSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human recombinant HDAC2 using Ac-Lys(Ac)-7-amino-4-methylcoumarin as substrate after 30 mins by trypsin-coupled fluorogenic assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 581.76, ALogP 3.39, HBA 5, HBD 4, PSA 140.47, QED 0.3
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: JNKZUXXSCHXOKY-HPEBZSCQSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 593.77, ALogP 3.54, HBA 5, HBD 4, PSA 140.47, QED 0.3
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human HDAC7 using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): CCC(NCCCC[C@@H](Nc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: QKBHUOCFQAXIBG-BPGUCPLFSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 using OmniMMP as substrate
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 419.52, ALogP 4.78, HBA 4, HBD 4, PSA 73.39, QED 0.24
Compound (SMILES): CCC(NCCCC[C@@H](Cc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: RKZDOJQKLCPUQZ-AIBWNMTMSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 using OmniMMP as substrate
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 418.53, ALogP 5.16, HBA 3, HBD 3, PSA 61.36, QED 0.27
Compound (SMILES): CCC(NCCCC[C@@H](Oc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: AWFIZJRPXRHSEA-BPGUCPLFSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 using OmniMMP as substrate
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 420.5, ALogP 4.75, HBA 4, HBD 3, PSA 70.59, QED 0.28
Compound (SMILES): CCC(NCCCC[C@@H](C[C@@H](OC)c1ccc(F)cc1)C(=O)NO)c1ccc(F)cc1
InChIKey: BPGDVHWVHMDFBK-IQWVOLIVSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 using OmniMMP as substrate
Measurement: Ki = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 434.53, ALogP 5.08, HBA 4, HBD 3, PSA 70.59, QED 0.23
Compound (SMILES): O=C(Cc1ccccc1)Oc1c(OC(=O)Cc2ccccc2)c(-c2ccc(O)cc2)c(O)c(O)c1-c1ccc(O)cc1
InChIKey: NOJUKCRPSUMHQQ-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Binding affinity to recombinant human 6His-tagged SENP1 catalytic domain expressed in Escherichia coli
Measurement: Ki = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 562.57, ALogP 6.14, HBA 8, HBD 4, PSA 133.52, QED 0.1
Compound (SMILES): Cc1nc2c(OC(F)F)cccc2n1-c1ccc(C(=O)NC2CC2)s1
InChIKey: VQQZSOVXMSWVFT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 using bufuralol as substrate after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.39, ALogP 3.89, HBA 5, HBD 1, PSA 56.15, QED 0.75
Compound (SMILES): Cc1nc2c(C#N)cccc2n1-c1ccc(C(=O)NC2CC2)s1
InChIKey: XRXYHTFKWSMTFI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells by whole cell voltage clamp assay
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 322.39, ALogP 3.16, HBA 5, HBD 1, PSA 70.71, QED 0.8
Compound (SMILES): CS(=O)(=O)N1CCC(Oc2ccc3c(c2)CCC2(CCN(C4CCC4)CC2)O3)CC1
InChIKey: BFKPZXXQVYWHKU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 434.6, ALogP 3.2, HBA 5, HBD 0, PSA 59.08, QED 0.73
Compound (SMILES): O=S(=O)(C1CC1)N1CCC(Oc2ccc3c(c2)CCC2(CCN(C4CCC4)CC2)O3)CC1
InChIKey: MMTAJJBCVXEVAY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.64, ALogP 3.73, HBA 5, HBD 0, PSA 59.08, QED 0.67
Compound (SMILES): CC(=O)N1CCC(Oc2ccc3c(c2)CCC2(CCN(C4CCC4)CC2)O3)CC1
InChIKey: RTNZBEUCZIJXRY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 398.55, ALogP 3.79, HBA 4, HBD 0, PSA 42.01, QED 0.78
Compound (SMILES): CC(C)C(=O)N1CCC(Oc2ccc3c(c2)CCC2(CCN(C4CCC4)CC2)O3)CC1
InChIKey: ZVASRANJKNGBRB-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.6, ALogP 4.42, HBA 4, HBD 0, PSA 42.01, QED 0.71
Compound (SMILES): O=C(C1CC1)N1CCC(Oc2ccc3c(c2)CCC2(CCN(C4CCC4)CC2)O3)CC1
InChIKey: KOAYFGOVRZLWGD-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.59, ALogP 4.18, HBA 4, HBD 0, PSA 42.01, QED 0.73
Compound (SMILES): Oc1ccc2[nH]c(-c3ccccc3)nc2c1CN1CCCCC1
InChIKey: FVHKIGHCUWTXCC-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 307.4, ALogP 3.92, HBA 3, HBD 2, PSA 52.15, QED 0.77
Compound (SMILES): Cc1cc2c(-c3ccc[nH]c3=O)c(C(=O)NS(=O)(=O)C3CC3)n(Cc3cc(F)ccc3F)c2cc1F
InChIKey: GXKRHWPFLHJAKI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 preincubated prior to substrate addition
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 515.51, ALogP 3.99, HBA 5, HBD 2, PSA 101.03, QED 0.41
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in HEK293 cells assessed as reduction in mitoxantrone efflux after 30 mins by flow cytometric analysis
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Protein-tyrosine kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13882
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): Nc1ncnc(Nc2ccc(Oc3ccc(Cl)cc3)cc2)n1
InChIKey: JSPXITPXMRLRIW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by PatchXpress voltage patch clamp assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 313.75, ALogP 3.64, HBA 6, HBD 2, PSA 85.95, QED 0.76
Compound (SMILES): Nc1cncc(Nc2ccc(Oc3ccc(OC(F)(F)F)cc3)cc2)n1
InChIKey: YBPKUYHMTYRITD-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 362.31, ALogP 4.49, HBA 6, HBD 2, PSA 82.29, QED 0.7
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of PDGFRalpha V561D mutant by TR-FRET based LanthaScreen assay
Measurement: IC50 = 2.38 nM (pChEMBL 8.619999885559082)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells by ITC analysis
Measurement: Kd = 194 nM (pChEMBL 6.710000038146973)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from human 5-HT2CR expressed in Flp-In HEK cell membranes incubated for 90 mins under dark condition by microbeta scintillation counting method
Measurement: Ki = 1860 nM (pChEMBL 5.730000019073486)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): Cc1c(NCCN(C)C)cc(Cl)cc1N1CCN(c2ncnc3[nH]nc(Br)c23)CC1
InChIKey: GPNUVUGMFDKAJH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1-mediated GSK3beta phosphorylation in human PC3 cells after 3 hrs by chemiluminescence assay
Measurement: IC50 = 4285 nM (pChEMBL 5.369999885559082)
Descriptors: MW 493.84, ALogP 3.38, HBA 7, HBD 2, PSA 76.21, QED 0.55
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)N(C)C(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: AAMHUKDMAMABLC-UAGACBDMSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using Ac-Lys(Ac)-7-amino-4-methylcoumarin as substrate after 30 mins by trypsin-coupled fluorogenic assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 581.76, ALogP 3.39, HBA 5, HBD 4, PSA 140.47, QED 0.3
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Arg-His-Lys(Ac)-Lys(Ac)-AMC as substrate after 30 mins by spectrophotometry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): CCC(NCCCC[C@@H](Nc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: QKBHUOCFQAXIBG-BPGUCPLFSA-N
Target: Lethal factor (SINGLE PROTEIN), Bacillus anthracis
UniProt: P15917
Assay: Inhibition of N-terminal 6-histine tagged Bacillus anthracis LF 263-C terminal catalytic domain using MCA-KKVYPYPME-Dap(Dnp)-NH2 as substrate after 4 hrs by FRET analysis
Measurement: Ki = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 419.52, ALogP 4.78, HBA 4, HBD 4, PSA 73.39, QED 0.24
Compound (SMILES): CCC(NCCCC[C@@H](Cc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: RKZDOJQKLCPUQZ-AIBWNMTMSA-N
Target: Lethal factor (SINGLE PROTEIN), Bacillus anthracis
UniProt: P15917
Assay: Inhibition of N-terminal 6-histine tagged Bacillus anthracis LF 263-C terminal catalytic domain using MCA-KKVYPYPME-Dap(Dnp)-NH2 as substrate after 4 hrs by FRET analysis
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 418.53, ALogP 5.16, HBA 3, HBD 3, PSA 61.36, QED 0.27
Compound (SMILES): CCC(NCCCC[C@@H](Oc1cc(C)c(F)c(C)c1)C(=O)NO)c1ccc(F)cc1
InChIKey: AWFIZJRPXRHSEA-BPGUCPLFSA-N
Target: Lethal factor (SINGLE PROTEIN), Bacillus anthracis
UniProt: P15917
Assay: Inhibition of N-terminal 6-histine tagged Bacillus anthracis LF 263-C terminal catalytic domain using MCA-KKVYPYPME-Dap(Dnp)-NH2 as substrate after 4 hrs by FRET analysis
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 420.5, ALogP 4.75, HBA 4, HBD 3, PSA 70.59, QED 0.28
Compound (SMILES): CCC(NCCCC[C@@H](C[C@@H](OC)c1ccc(F)cc1)C(=O)NO)c1ccc(F)cc1
InChIKey: BPGDVHWVHMDFBK-IQWVOLIVSA-N
Target: Lethal factor (SINGLE PROTEIN), Bacillus anthracis
UniProt: P15917
Assay: Inhibition of N-terminal 6-histine tagged Bacillus anthracis LF 263-C terminal catalytic domain using MCA-KKVYPYPME-Dap(Dnp)-NH2 as substrate after 4 hrs by FRET analysis
Measurement: Ki = 0.27 nM (pChEMBL 9.569999694824219)
Descriptors: MW 434.53, ALogP 5.08, HBA 4, HBD 3, PSA 70.59, QED 0.23
Compound (SMILES): O=C(Cc1ccccc1)Oc1c(OC(=O)Cc2ccccc2)c(-c2ccc(O)cc2)c(O)c(O)c1-c1ccc(O)cc1
InChIKey: NOJUKCRPSUMHQQ-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of full-length recombinant human 6His-tagged SENP1 expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by addition of SUMO1-AMC as substrate measured after 1 hr by fluorescence analysis
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 562.57, ALogP 6.14, HBA 8, HBD 4, PSA 133.52, QED 0.1
Compound (SMILES): Cc1nc2c(OC(F)F)cccc2n1-c1ccc(C(=O)NC2CC2)s1
InChIKey: VQQZSOVXMSWVFT-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells by whole cell voltage clamp assay
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 363.39, ALogP 3.89, HBA 5, HBD 1, PSA 56.15, QED 0.75
Compound (SMILES): Oc1ccc2[nH]c(-c3ccccc3)nc2c1CN1CCCCC1
InChIKey: FVHKIGHCUWTXCC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 307.4, ALogP 3.92, HBA 3, HBD 2, PSA 52.15, QED 0.77
Compound (SMILES): Cc1cc2c(-c3ccc[nH]c3=O)c(C(=O)NS(=O)(=O)C3CC3)n(Cc3cc(F)ccc3F)c2cc1F
InChIKey: GXKRHWPFLHJAKI-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV NS5B polymerase
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 515.51, ALogP 3.99, HBA 5, HBD 2, PSA 101.03, QED 0.41
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 in topotecan-cultured human MCF7 cells using Hoechst 33342 as substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 707 nM (pChEMBL 6.150000095367432)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): Nc1cncc(Nc2ccc(Oc3ccc(OC(F)(F)F)cc3)cc2)n1
InChIKey: YBPKUYHMTYRITD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 362.31, ALogP 4.49, HBA 6, HBD 2, PSA 82.29, QED 0.7
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET by TR-FRET based LanthaScreen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by MST assay
Measurement: Kd = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125l]N 6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide from recombinant human A3AR expressed in CHO cell membranes after 60 mins by gamma counting method
Measurement: Ki = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human HDAC9 using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): O=C(Cc1ccccc1)Oc1c(OC(=O)Cc2ccccc2)c(-c2ccc(O)cc2)c(O)c(O)c1-c1ccc(O)cc1
InChIKey: NOJUKCRPSUMHQQ-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of recombinant human 6His-tagged SENP1 catalytic domain expressed in Escherichia coli preincubated for 15 mins followed by addition of SUMO1-AMC as substrate measured after 1 hr by fluorescence analysis
Measurement: IC50 = 1890 nM (pChEMBL 5.71999979019165)
Descriptors: MW 562.57, ALogP 6.14, HBA 8, HBD 4, PSA 133.52, QED 0.1
Compound (SMILES): Oc1ccc2[nH]c(-c3ccccc3)nc2c1CN1CCCCC1
InChIKey: FVHKIGHCUWTXCC-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Antagonist activity at human NR1-NR2A receptor by FLIPR-based Ca2+ flux assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 307.4, ALogP 3.92, HBA 3, HBD 2, PSA 52.15, QED 0.77
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 in human KB-V1 cells using calcein-AM as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 = 6756 nM (pChEMBL 5.170000076293945)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 by TR-FRET based LanthaScreen assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by qPCR assay
Measurement: Kd = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60612
Assay: Displacement of [3H]N6-R-phenylisopropyladenosine from mouse A1A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of recombinant human HDAC10 using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of human ABCC1 transfected in MDCK2-MRP1 cells using calcein-AM as substrate measured after 1 hr by fluorescence assay
Measurement: IC50 = 3599 nM (pChEMBL 5.440000057220459)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 by TR-FRET based LanthaScreen assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by ITC analysis
Measurement: Kd = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5-N-methyluronamide from mouse A3A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant human HDAC11 using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)c3cc(=O)c4c(OCc5ccc(Br)cc5)cccc4o3)c2c1
InChIKey: YOURSKBAKQLDQW-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of sulfasalazine-stimulated ABCB1 ATPase activity (unknown origin) expressed in baculovirus infected Sf9 insect cells using ATP as substrate measured after 1 hr by colorimetric assay
Measurement: IC50 = 745 nM (pChEMBL 6.130000114440918)
Descriptors: MW 547.41, ALogP 5.6, HBA 5, HBD 2, PSA 93.56, QED 0.26
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 autophosphorylation by cell based assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of GST-tagged LRRK2 (1326 to 2527 amino acids) G2019S mutant (unknown origin)
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Inhibition of 5HT2B (unknown origin)
Measurement: Ki = 641 nM (pChEMBL 6.190000057220459)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 in human HeLa cells nuclear extract using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3
Compound (SMILES): Nc1c(-c2ccc(F)cc2)c(-c2ccncc2)nn1-c1c(Cl)cc(Cl)cc1Cl
InChIKey: MOHYPRXHKRXDSE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase Assay: FlashPlates from Perkin Elmer (Boston, Mass., USA) with a 50 μl reaction volume are used. The reaction cocktail was pipetted in 4 steps in the following order: 15 μl of ATP solution (in H2O), 20 μl of assay buffer (see below), 5 μl of test sample in 10% DMSO, 10 μl of enzyme/substrate mixture (in H2O). The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [γ-33P]-ATP (approx. 8×10^5 cpm per well), protein kinase (variable amounts; see Table 1), and substrate (variable amounts). Certain assays also contained 1 mM CaCl2, 4 mM EDTA, 5 μg/ml Phosphatidylserine and 1 μg/ml 1.2-Dioleyl-glycerol. The MYLK2, CAMK1D, CAMK2A, CAMK2B, CAMK2D, CAMK4, CAMKK2, DAPK2 and EEF2K assays additionally contained 1 μg/ml Calmodulin and 0.5 mM CaCl2. The PRKG1 and PRKG2 assays additionally contained 1 μM cGMP. Recombinant Protein Kinases: All protein kinases were expressed in Sf9 insect cells or in E. coli as recombinant GST-fusion proteins or His-tagged proteins. All kinases were produced from human cDNAs, except JAK2, for which the mouse cDNA was used. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen). The purity of the protein kinases was examined by SDS-PAGE/coomassie staining. The identity of the protein kinases was checked by mass spectroscopy. Assays were made under license from Chemicon International Inc. for JAK2. The reaction cocktails were incubated at 30° C. for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H3PO4, plates were aspirated and washed two times with 200 μl 0.9% (w/v) NaCl. All assays were performed with a BeckmanCoulter Biomek 2000/SL robotic system. Incorporation of 33Pi (counting of "cpm") was determined with a microplate scintillation counter (Microbeta, Wallac).
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 433.7, ALogP 6.28, HBA 4, HBD 1, PSA 56.73, QED 0.41
Compound (SMILES): COc1cc(O)c2c(c1)CCC[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O
InChIKey: QXPNJMHRUZCEAP-UXBSLASESA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A kinase by Caliper mobility shift assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.39, ALogP 1.52, HBA 7, HBD 3, PSA 113.29, QED 0.65
Compound (SMILES): COc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: IWMCPJZTADUIFX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 G2019S mutant (1326 to 252 aa) (unknown origin) stably expressed in HEK293 cell lysate using [gamma-32P] after 15 mins by Cerenkov counting method
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 570.7, ALogP 3.44, HBA 9, HBD 1, PSA 97.38, QED 0.49
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NC(C3CC3)C3CC3)nc(Cl)nc21
InChIKey: XJBGUZYJXHUHPS-HLXQIYJLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 using tolbutamide as substrate
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 375.86, ALogP 1.99, HBA 7, HBD 3, PSA 96.09, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H](C)NC(=O)C[C@H](CC(C)C)NC(=O)[C@H](Cc2cccc3ccccc23)NC1=O
InChIKey: HFDUFQFVUVYKCX-MQIQBBKZSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of HDAC3-NCoR2 in human HeLa cells nuclear extract using Fluor-de-Lys as substrate after 30 mins by spectrophotometry
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 578.75, ALogP 3.72, HBA 5, HBD 4, PSA 133.47, QED 0.3