lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(Sc1ccncc1-c1ccc(C#N)c2ccccc12)C(=O)[O-].[Na+]
InChIKey: SDJHWWWQAIRKKV-UHFFFAOYSA-M
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 membrane vesicles assessed as inhibition of ATP-induced 14C-uric acid uptake preincubated for 15 mins followed by incubation with ATP and substrate for 5 mins by liquid scintillation counting analysis
Measurement: IC50 = 18750 nM (pChEMBL 4.730000019073486)
Descriptors: MW 348.43, ALogP 4.73, HBA 4, HBD 1, PSA 73.98, QED 0.69
Compound (SMILES): CCN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: CXRFVRQTMSLWOK-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/cyclin-D3 (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 447.52, ALogP 2.85, HBA 7, HBD 2, PSA 86.28, QED 0.62
Compound (SMILES): CCS(=O)(=O)Nc1ccc(OCCOCCOCCOCCOc2ccc(NS(=O)(=O)CC)cc2-c2cn(C)c(=O)c3ccccc23)c(-c2cn(C)c(=O)c3ccccc23)c1
InChIKey: VGOFJMULWAVDMV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4-T (unknown origin)
Measurement: Kd = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 875.03, ALogP 5.76, HBA 13, HBD 2, PSA 182.49, QED 0.08
Compound (SMILES): Cc1cc2ncccc2cc1Nc1ncc2c(n1)n([C@@H]1CNC[C@H]1F)c(=O)n2C
InChIKey: VHGGSMHLKWIQAF-CZUORRHYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK (unknown origin) using EPPLSQEAFADLWKK peptide as substrate preincubated with compound for 30 mins followed by substrate addition and further incubated for 40 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 393.43, ALogP 2.21, HBA 8, HBD 2, PSA 89.66, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)n2[nH]c(=O)c3ccccc3c2=O)cc1
InChIKey: YWCOXNHQOGDABA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometry based esterase assay
Measurement: Ki = 6.32 nM (pChEMBL 8.199999809265137)
Descriptors: MW 345.34, ALogP 0.03, HBA 6, HBD 2, PSA 132.09, QED 0.68
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CNS(=O)(=O)c1ccc(Oc2ccccc2)cc1)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: VETMYWAUBVBABL-KNIQQNQGSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 = 6469 nM (pChEMBL 5.190000057220459)
Descriptors: MW 948.09, ALogP -1.17, HBA 13, HBD 9, PSA 344.69, QED 0.05
Compound (SMILES): Nc1nc2cc(-c3nc(N4CCOCC4)nc(N4CCOCC4)n3)ccc2o1
InChIKey: LOQNSAZUXOBMAX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) in presence of [33P]-ATP incubated for 2 hrs by hotspot kinase assay
Measurement: IC50 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 383.41, ALogP 0.94, HBA 10, HBD 1, PSA 115.66, QED 0.7
Compound (SMILES): COc1cc(C(=O)N2CCCC2)ccc1-c1ccnc2[nH]c(C3CCNCC3)cc12
InChIKey: VBWQPLLCGUWXEE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) using FL-Ahx-QSPKKG-CONH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 404.51, ALogP 3.94, HBA 4, HBD 2, PSA 70.25, QED 0.69
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSCCCSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: HJERQRDKWIWHPW-RJVDFBNNSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 2097.48
Compound (SMILES): O=C(Cc1cccnc1)N[C@@H](Cc1coc2ccccc12)B(O)O
InChIKey: ZKQWMHKXJMGVFF-INIZCTEOSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 646 nM (pChEMBL 6.190000057220459)
Descriptors: MW 324.15
Compound (SMILES): O=c1[nH]c2cncnc2n1[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: HFWMSMHRYHEPNX-JXOAFFINSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Agonist activity at human P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 10964.78 nM (pChEMBL 4.960000038146973)
Descriptors: MW 508.17, ALogP -1.92, HBA 13, HBD 7, PSA 273.08, QED 0.19
Compound (SMILES): O=S(=O)(c1ccccc1)N1CCc2cc(C3CC3NC3CC4(CCNCC4)C3)ccc21
InChIKey: YKEKIWUQGGNVGF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 437.61, ALogP 3.42, HBA 4, HBD 2, PSA 61.44, QED 0.75
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C)n2)ccn1
InChIKey: HINOQCZIDBNXEI-FQEVSTJZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 372.47, ALogP 3.77, HBA 6, HBD 2, PSA 99.36, QED 0.77
Compound (SMILES): Cc1cccc(N2CCN(CCCN3C(=O)CCc4ccccc43)CC2)c1.O=C(O)C(=O)O
InChIKey: IURIFAMWYUXKNB-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 363.51, ALogP 3.49, HBA 3, HBD 0, PSA 26.79, QED 0.81
Compound (SMILES): C#CCN(Cc1ccc(-c2ccc(O)c(C(=O)O)c2)o1)Cc1ccc(-c2ccc(O)c(C(=O)O)c2)o1.N.N
InChIKey: XBDGWQHTCISIHH-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of human recombinant LDHA using pyruvate as substrate preincubated for 10 mins followed by substrate addition and measured every 60 sec for 10 mins in the presence of NADH by fluorescence assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 487.46, ALogP 4.65, HBA 7, HBD 4, PSA 144.58, QED 0.25
Compound (SMILES): CCCN1CCNC(c2cccc(C3COCCN3C(=O)OCc3ccccc3)c2)C1
InChIKey: WGHXXFQMHFSUAW-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-ditolylguanidine from human sigma 2 receptor/TMEM97 transfected in human HEK293T cells assessed as inhibition constant in presence of (+)-pentazocine by radioligand competition binding assay
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 423.56, ALogP 3.75, HBA 5, HBD 1, PSA 54.04, QED 0.77
Compound (SMILES): Cn1nncc1-c1cnn([C@H](CCOC(F)F)c2ccc(-c3c(-n4cc(Cl)nn4)ccc(Cl)c3F)c[n+]2[O-])c1
InChIKey: BETDGMHNHGHORO-MRXNPFEDSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human plasma coagulation factor Xa using CH3SO2-D-CHA-Gly-Arg-AMC-AcOH as substrate preincubated for 5 to 15 mins followed by substrate addition and measured at 5 mins interval for 2 hrs by fluorescence based envision plate reader method
Measurement: IC50 > 98000 nM (pChEMBL 4.008999824523926)
Descriptors: MW 580.36, ALogP 4.22, HBA 10, HBD 0, PSA 115.41, QED 0.19
Compound (SMILES): C#CCN(C)CCCOc1cc(NC(=O)CCCCCCC(=O)NO)ccc1Cl
InChIKey: SCESJGHIRHHUMV-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 (379 to 382 residues) using RHKKAc-AMC fluorogenic peptide as substrate by fluorescence assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 423.94, ALogP 3.46, HBA 5, HBD 3, PSA 90.9, QED 0.18
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccccc1
InChIKey: WVEITDZFTWWPRV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 32.3 nM (pChEMBL 7.489999771118164)
Descriptors: MW 375.44, ALogP 5.43, HBA 4, HBD 1, PSA 59.39, QED 0.44
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1c(C#N)ccc(OC)c1F
InChIKey: SPXOTFDBWDBJRN-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibitory Activity Assay: Example compounds were evaluated for inhibition of the human activated kallikrein enzyme in two formats of an assay employing a fluorogenic peptide substrate. In one assay format, the concentrations of reagents were as follows: 20 mM Tris pH 7.5, 1 mM EDTA, 150 mM sodium chloride, 0.1% PEG-400, 0.1% Triton X-100, 500 pM activated kallikrein enzyme, 300 uM Pro-Phe-Arg-7-amido-4-methylcoumarin substrate. Prior to reaction initiation with substrate, enzyme and inhibitors were preincubated for 30 min at RT. After initiation with substrate, reactions were incubated for 10 min at RT and fluorescence emission at 460 nm from 380 nm excitation measured with a microplate reader. In another assay format, the concentrations of reagents were as follows: 20 mM Tris pH 7.5, 1 mM EDTA, 150 mM sodium chloride, 0.1% PEG-400, 0.1% Triton X-100, 5 pM activated kallikrein enzyme, 300 uM Pro-Phe-Arg-7-amido-4-methylcoumarin substrate. Prior to reaction initiation with substrate, enzyme and inhibitors were preincubated for 30 min at RT. After initiation with substrate, reactions were incubated for 18 h at RT and fluorescence emission at 460 nm from 380 nm excitation measured with a microplate reader.
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 515.55, ALogP 3.24, HBA 8, HBD 1, PSA 111.17, QED 0.35
Compound (SMILES): COC(C)(C)C(=O)NC(=O)Nc1ccc(Oc2ccnc(-c3cnn(C)c3)c2)c(C)n1
InChIKey: QGLUQQCIZIEJHF-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 424.46, ALogP 3.05, HBA 8, HBD 2, PSA 120.26, QED 0.62
Compound (SMILES): Cl.Oc1ccc(C2NCCc3c2[nH]c2ccc(F)cc32)cc1
InChIKey: YPMAXHABWKVUGO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 282.32, ALogP 3.25, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): CNc1nccc(-c2n[nH]c3nc(N4CCC(C)(N)CC4)cnc23)c1Cl
InChIKey: XLKDUTBYZJONNW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 372.86, ALogP 2.43, HBA 7, HBD 3, PSA 108.64, QED 0.65
Compound (SMILES): CC(C)c1ccccc1C(=O)N(CC(=O)NC(C)(C)C)Cc1ccc(C(=O)NO)cc1F
InChIKey: ICGXHGQIMMAKJH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC6 (1 to 1215 residues) expressed in Sf9 insect cells using Z-Lys(Ac)-AMC as fluorogenic substrate incubated for 90 mins by microplate reader analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 443.52, ALogP 3.63, HBA 4, HBD 3, PSA 98.74, QED 0.45
Compound (SMILES): COc1ccc(S(=O)(=O)n2cc(C(F)F)c3ccc(F)cc32)cc1N1CCNCC1
InChIKey: NVURPAJUKWGEBE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Antagonist activity at recombinant human 5HT6R expressed in CHO cells assessed as inhibition of 5HT-stimulated cAMP accumulation incubated for 4 hrs by luminescence counter analysis
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 439.46, ALogP 3.37, HBA 6, HBD 1, PSA 63.57, QED 0.66
Compound (SMILES): CN1CCN(C(=O)c2ccc(Nc3nc(N)c(C(=O)c4c(Cl)cccc4Cl)s3)cc2)CC1
InChIKey: DQMDXHWHDMGPCC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 490.42, ALogP 4.39, HBA 7, HBD 2, PSA 91.56, QED 0.52
Compound (SMILES): CCS(=O)(=O)n1cc2c3ccc(cc31)OCCCCCCOc1cc(c(Cl)cc1N1CCOCC1)Nc1ncc(Cl)c-2n1
InChIKey: DRZQMWISKZKPBX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR del19/T790M/C797S triple mutant (unknown origin) in presence of ATP by FRET assay
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 646.6, ALogP 6.51, HBA 10, HBD 1, PSA 107.81, QED 0.27
Compound (SMILES): O=S1(=O)CC=Cc2ccc(-c3ccc(F)cc3)cc2O1
InChIKey: YPJIOQROYSMZJM-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human recombinant CA2 assessed as inhibition constant incubated for 6 hrs prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 290.31, ALogP 3.23, HBA 3, HBD 0, PSA 43.37, QED 0.76
Compound (SMILES): COC(=O)c1ccc(-c2ccc3ncc4nc(C)n(-c5ccc(F)cc5)c4c3c2)cc1
InChIKey: XAQGTBDURFAHOJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 336.1 nM (pChEMBL 6.46999979019165)
Descriptors: MW 411.44, ALogP 5.47, HBA 5, HBD 0, PSA 57.01, QED 0.37
Compound (SMILES): Fc1ccc(COC2CCN(Cc3cc4ccc(Cl)cc4[nH]3)CC2)cc1F
InChIKey: AFLWHRXREOAJGY-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH23390 from human D5 receptor expressed in HEK293 cell membrane by competitive inhibition based analysis
Measurement: Ki = 3986.6 nM (pChEMBL 5.400000095367432)
Descriptors: MW 390.86, ALogP 5.28, HBA 2, HBD 1, PSA 28.26, QED 0.64
Compound (SMILES): COc1ccc(-n2cc3cnc(NCC(F)(F)F)nc3c(-c3ccc(Br)cc3)c2=O)cc1
InChIKey: QHXQQFITXAUNPR-UHFFFAOYSA-N
Target: S-adenosylmethionine synthase isoform type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31153
Assay: Inhibition of MAT2A (unknown origin) using L-methionine and ATP as substrate preincubated with compound for 10 mins followed by substrate addition and measured after 60 mins by kinase-glo max reagent based microplate reader analysis
Measurement: IC50 = 56.1 nM (pChEMBL 7.25)
Descriptors: MW 505.29, ALogP 5.19, HBA 6, HBD 1, PSA 69.04, QED 0.4
Compound (SMILES): COc1cc(N2CCN(CCCCCCCCCCCCNC(=O)CC34CC5CC(CC(C5)C3)C4)CC2)ccc1Nc1ncc2c(C)cc(=O)n(-c3cccc(NC(=O)C(C)C)c3)c2n1
InChIKey: JSRYZGUADWFRFX-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Induction of AKT3 degradation in human NCI-H1975 cells assessed as reduction in AKT3 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 887.23, ALogP 10.18, HBA 10, HBD 3, PSA 133.72, QED 0.07
Compound (SMILES): COc1cc(N2CCC3(CCNCC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: LKGLPOBFCOFWMI-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) using biotinylated substrate incubated for 1 hr in the presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 555.06, ALogP 5.84, HBA 8, HBD 3, PSA 91.41, QED 0.31
Compound (SMILES): N#Cc1ccc(C[C@@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCc3ccccc3C2)cc1
InChIKey: TVFMIWUEXKUQEY-XMMPIXPASA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Antagonist activity at human FPR2 transfected in human HL-60 cells assessed as inhibition of WKYMVM-induced intracellular calcium mobilization preincubated for 10 mins followed by WKYMVM addition measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 442.49, ALogP 4.02, HBA 3, HBD 2, PSA 85.23, QED 0.63
Compound (SMILES): CCN(CC)C(=O)c1ccc2c(c1)nc(Cc1ccc(OC(=O)NCCCCCCN3CCc4ccccc4C3)cc1)n2CCC(C)C
InChIKey: YBILVISNRAVIPV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured every 30 sec for 3 mins by DTNB-based UV analysis
Measurement: IC50 = 9522 nM (pChEMBL 5.019999980926514)
Descriptors: MW 651.9, ALogP 7.86, HBA 6, HBD 1, PSA 79.7, QED 0.12
Compound (SMILES): CC(C)(C)c1nc(C23CCC(CN(C(=O)C45CC(F)(C4)C5)c4cccc(-c5nc(C6CC6)no5)c4)(CC2)CC3)no1
InChIKey: KMWDADSUZQXCTH-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant CYP2C9 (unknown origin) using fluorogenic substrate preincubated for 15 min followed by NADPH addition measured after 2 hrs by fluorescence method
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 559.69, ALogP 6.81, HBA 7, HBD 0, PSA 98.15, QED 0.31
Compound (SMILES): CCOC(=O)c1nc(-c2ccc(OC)cc2)oc1C
InChIKey: DAFRLXQGMZPMLA-UHFFFAOYSA-N
Target: RISC-loading complex subunit TARBP2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15633
Assay: Inhibition of TRBP in human HeLa cells transfected with pCIneo-luciferase microRNA-21 by measuring effective concentration in inhibition of microRNA-21 biogenesis by luciferase reporter assay
Measurement: EC50 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 261.28, ALogP 2.84, HBA 5, HBD 0, PSA 61.56, QED 0.79
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@H](NC(=O)[C@@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-UBHSHLNASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): CCCC[Si](C)(C)c1cc(O)c(C2CCCC2)c(OC)c1
InChIKey: WKVNYGJWBHBRPZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at recombinant human CB2 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin stimulation and measured after 15 mins by HTRF assay
Measurement: EC50 = 999.6 nM (pChEMBL 6)
Descriptors: MW 306.52
Compound (SMILES): COc1ccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)c(O)c1
InChIKey: POCNIPUWZPJPSF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 328.8, ALogP 3.77, HBA 3, HBD 3, PSA 57.28, QED 0.67
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(I)cc3)nc3ccccc3c2[nH]1
InChIKey: PMLCQIVFRJHHRF-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver Microsome using phenacetin as substrate in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 484.39, ALogP 7.14, HBA 3, HBD 2, PSA 53.6, QED 0.27
Compound (SMILES): CC(C)(C)CNC(=S)Nc1ccc2c(c1)CCN2Cc1ccc(N=O)cc1
InChIKey: WPRKZXRSIVTSOS-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH assessed as reduction in 6-methoxynaphthaldehyde formation using PHOME as substrate preincubated for 1 min followed by substrate addition and measured after 60 mins by fluorescence based analysis
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 382.53, ALogP 4.98, HBA 4, HBD 2, PSA 56.73, QED 0.56
Compound (SMILES): Cc1ccc(-c2c(CN3CCOCC3)nc3scc(C(=O)NN)n23)cc1
InChIKey: MSIRVCGEZTUEOG-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli incubated for 15 mins and measured by ELISA
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 371.47, ALogP 1.81, HBA 7, HBD 2, PSA 84.89, QED 0.42
Compound (SMILES): Nc1nc(N)nc(NCCCCN2CCN(c3cccc(Cl)c3Cl)CC2)n1
InChIKey: ZHPOMVVVPOMELJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK293 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 411.34, ALogP 2.36, HBA 8, HBD 3, PSA 109.22, QED 0.6
Compound (SMILES): Cc1ncc(CC(=O)Nc2cc([C@H]3CC[C@@H](OC(=O)NC(C)C)C3)[nH]n2)s1
InChIKey: UUPJXVBCBPIVKZ-QWHCGFSZSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Biochemical Assay: The purpose of CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 full length catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2, CPC Scientific, Sunnyvale, Calif.) (SEQ ID NO:1). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Matl enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (±inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA.
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 391.5, ALogP 3.13, HBA 6, HBD 3, PSA 109, QED 0.7
Compound (SMILES): Cc1cc(N2CCC(c3ccccc3)C2)n2ncc(-c3ccccn3)c2n1
InChIKey: SCEFCHMRVURBBT-UHFFFAOYSA-N
Target: G-protein coupled receptor 39 (SINGLE PROTEIN), Homo sapiens
UniProt: O43194
Assay: Positive allosteric activity at human GPR39 receptor expressed in CHO cells assessed as increase in zn2+ induced ca2+ flux
Measurement: EC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 355.45, ALogP 4.09, HBA 5, HBD 0, PSA 46.32, QED 0.56
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@@H]1CCc2ccccc21
InChIKey: BKYUUBOSZSVARW-CHXHCODASA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: Antagonist activity at N-terminal His-tagged cIAP1-BIR3 domain (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 679.77, ALogP 1.93, HBA 8, HBD 4, PSA 163.01, QED 0.22
Compound (SMILES): CC(C)Oc1ccc(-c2cn(-c3ccc(CN4CC(C(=O)[O-])C4)cc3)nn2)cc1C(F)(F)F.[Na+]
InChIKey: XEQYOLZTLGVXCN-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.46, ALogP 4.26, HBA 6, HBD 1, PSA 80.48, QED 0.57
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@]4(C)C(=O)c4ccc6ccccc6c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: XEIGWVZJLXNMIJ-LEKWGUGTSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat DOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 338.4 nM (pChEMBL 6.46999979019165)
Descriptors: MW 549.71, ALogP 6.35, HBA 5, HBD 0, PSA 48, QED 0.34
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4OCc4cccc(OC)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: BFRLXNXMJLTBAD-MDIPFLTBSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 38018.94 nM (pChEMBL 4.420000076293945)
Descriptors: MW 512.57, ALogP 1.14, HBA 11, HBD 4, PSA 152.88, QED 0.33
Compound (SMILES): O=C(N/N=C/c1ccc(N2CCCCC2)cc1)c1ccc(CN2CCC(CO)CC2)cc1
InChIKey: GJSXFHLPQQQFLU-OVVQPSECSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AchE assessed as inhibition constant
Measurement: Ki = 6238 nM (pChEMBL 5.210000038146973)
Descriptors: MW 434.58, ALogP 3.65, HBA 5, HBD 2, PSA 68.17, QED 0.52
Compound (SMILES): CCN(CC)c1ccc2c(-c3ccc(S(=O)(=O)NCCCCCC(=O)NCCNCCCC4(c5ccccc5)OC(C)(C)c5ccccc54)cc3S(=O)(=O)[O-])c3ccc(=[N+](CC)CC)cc-3oc2c1
InChIKey: RPQOVOZBHWXNBF-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]-citalopram from SERT in Sprague-Dawley rat brainstem incubated for 60 mins by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 978.29, ALogP 8.3, HBA 10, HBD 3, PSA 173.12, QED 0.02
Compound (SMILES): Cc1nc(N2CCC(C)(N)CC2)cc(=O)n1-c1cccc(Cl)c1Cl
InChIKey: HGAOJDKDTHZJNB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2, E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 367.28, ALogP 3.17, HBA 5, HBD 1, PSA 64.15, QED 0.89
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ccc(C#N)cn3)ccc2F)CS(=O)(=O)[C@](C)(CF)C(=N)N1
InChIKey: GNWNOQLLBKOHTC-RBUKOAKNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of MK499 from human ERG expressed in HEK membrane by radio ligand binding competition assay
Measurement: IC50 = 25560 nM (pChEMBL 4.590000152587891)
Descriptors: MW 448.46, ALogP 1.68, HBA 7, HBD 3, PSA 148.69, QED 0.64
Compound (SMILES): COC(=O)C1CN(Cc2ccc(C3=NOC(c4ccccc4)C3)cc2)C1
InChIKey: OQHRDXNTCGJJMD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 350.42, ALogP 3.16, HBA 5, HBD 0, PSA 51.13, QED 0.78
Compound (SMILES): Cc1cc(C(=O)NCc2ccc(CN)cc2)c(C)n1Cc1cccc(-c2cccnc2)n1
InChIKey: PBAAHHAGMWJRRK-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition Assay: KLK1 inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stürzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human KLK1 (Callbiochem) was incubated at 37° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 425.54, ALogP 4, HBA 5, HBD 2, PSA 85.83, QED 0.47
Compound (SMILES): Cc1ccc(C(=O)N(CCCNC(=O)CCCCCCCCN2CCN(S(=O)(=O)c3ccc(NC(=S)NCc4cccnc4)cc3)CC2)[C@@H](c2nc3cc(Cl)ccc3c(=O)n2Cc2ccccc2)C(C)C)cc1
InChIKey: LZCAADBODOWVEZ-OIVUAWODSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Induction of NAMPT degradation in human A2780 cells
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 1046.8
Compound (SMILES): COC(=O)C1CCN(C(=O)c2cccc(NCc3cnc4nc(N)nc(N)c4n3)c2)CC1
InChIKey: WZBPRUPXHZYYIT-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 436.48, ALogP 1.22, HBA 10, HBD 3, PSA 162.24, QED 0.5
Compound (SMILES): O=C(COc1ccc(-c2ccccc2)cc1)NCC1CCN(Cc2ccccc2)CC1
InChIKey: OTKIZSHLVPXZAG-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human recombinant FAAH using AMC-AA as substrate preincubated with enzyme for 10 mins followed by substrate addition for 2 hrs by fluorometric analysis
Measurement: IC50 = 23300 nM (pChEMBL 4.630000114440918)
Descriptors: MW 414.55, ALogP 4.76, HBA 3, HBD 1, PSA 41.57, QED 0.58
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4ccsc4)nc3)ncc2Cl)c1
InChIKey: CMLIHNXRVQWYBQ-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 = 215.6 nM (pChEMBL 6.670000076293945)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: MNMRRFAISKIFMJ-SLHDEKGNSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at human adenosine A2A receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 3311.31 nM (pChEMBL 5.480000019073486)
Descriptors: MW 468.51, ALogP 0.99, HBA 10, HBD 4, PSA 143.65, QED 0.4
Compound (SMILES): O=C(O)c1ccc(SC2=NS(=O)(=O)c3ccccc32)cc1
InChIKey: LABKIXIZKCQJOX-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition of human pyruvate kinase in embryonic cells
Measurement: IC50 = 16300 nM (pChEMBL 4.789999961853027)
Descriptors: MW 319.36, ALogP 2.63, HBA 4, HBD 1, PSA 83.8, QED 0.92
Compound (SMILES): Cc1ccc(C2CCN(c3ccc(Nc4nccc(-c5ccc(C(=O)NCC#N)cc5)n4)cc3)CC2)o1
InChIKey: RCIYSHDQTFGLIG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 kinase domain
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 492.58, ALogP 5.43, HBA 7, HBD 2, PSA 107.08, QED 0.33
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(F)nc1
InChIKey: PGZQEUGRRIQARD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 55.2 nM (pChEMBL 7.260000228881836)
Descriptors: MW 394.41, ALogP 4.96, HBA 5, HBD 1, PSA 72.28, QED 0.42
Compound (SMILES): Cc1nc(NC(=O)c2cccc(-c3cnn(C)c3)n2)cc(N2CC[C@@H](C(C)(C)O)C2)n1
InChIKey: UPSNQHGCEYRORJ-MRXNPFEDSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) assessed as substrate phosphorylation using coumarin and fluorescein-labeled peptide as substrate incubated for 1 hr by Z'-LYTE kinase assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 421.51, ALogP 2.43, HBA 8, HBD 2, PSA 109.06, QED 0.65
Compound (SMILES): CCCNNC(=O)c1cnc(N2CCN(Cc3c[nH]c4ccccc34)CC2)nc1
InChIKey: MAEKVVCEBJELGT-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 393.5, ALogP 1.92, HBA 6, HBD 3, PSA 89.18, QED 0.42
Compound (SMILES): N#Cc1ccc2c(Nc3ccc4[nH]nc(-c5ccncc5)c4c3)cccc2c1
InChIKey: AZGKLZGDJGQVGI-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of wild type pcDNA5FRT-TO-GFP fused - LRRK2 (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 361.41, ALogP 5.39, HBA 4, HBD 2, PSA 77.39, QED 0.45
Compound (SMILES): COc1cc2c(C)nnc(N[C@H](C)c3cccc(C(F)(F)F)c3C)c2cc1OC
InChIKey: SUSQYYGPLOUGJB-GFCCVEGCSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibiting SOS1-Mediated GTP Nucleotide Exchange by Blocking Mant-GDP Exchange: Table 24: This Example illustrates that exemplary compounds of the present invention prevent KRas-mediated GTP nucleotide exchange mediated by SOS1 to inhibit KRas activity thereby inhibiting the generation of the downstream effector pERK. MKN1 cells (15,000/w) or H358 (30,000/w) were seeded in a black clear flat bottom 96-well cell culture plate (Corning, #3904) and incubated at 37° C. overnight. Assay day 1, cells were dosed with compounds of Formula (I) with a 10 μm starting concentration and serially diluted 3× for a total of 9 concentrations. The cells were incubated for approximately 0.5-1 hour with the compounds solubilized in DMSO at 37° C. Cells were immediately fixed by adding 50 μL of 4% formaldehyde to all wells in a fume hood and the plates were incubated for 20 minutes at room temperature. The formaldehyde was discarded from the plates and 150 μL of ice-cold methanol was added to permeabilize the cells for 10 minutes at −20° C. The methanol was discarded from each of the plates and any liquid remaining in the plate by tapping the plate against paper towels. Cells were then blocked with 150 μL of Odyssey blocking buffer (LI-COR Biosciences #927-50010) using 0.05% Tween for 1 hour at room temperature on a shaker. The blocking buffer was discarded and 50 μL of primary antibodies pERK (cell signaling Technology #9101L; Rabbit, 1:500) and GapDH (Millipore #MAB34; Mouse, 1:5000) diluted in Odyssey blocking buffer was added. The plates were incubated overnight at 4° C. on a shaker. On Assay Day 2, the primary antibody solution was removed. Each plate was washed 3× times with 150 μL of 1×PBST (PBS+0.1% Tween 20) and incubated with 50 μL of secondary antibodies: Anti-Rabbit (LI-COR Biosciences #926-32211) and Anti-Mouse (LI-COR Biosciences #68070) at 1:800 dilution in Odyssey blocking buffer with Tween at room temperature on a shaker for 2 hours (protected from light). The secondary antibody solution as removed and each plate was washed with PBST 3× times. Any liquid remaining was discarded and the plate was imaged using the Licor Odyssey machine according to the manufacturer's instruction, using a set focus length at 3 mm and both 800 nm and 700 nm filters. The GAPDH normalized scan values for each well were divided by the average of vehicle wells to get the % of pERK inhibition. The IC50 values were then calculated with the Graph pad Prism software.
Measurement: IC50 = 327 nM (pChEMBL 6.489999771118164)
Descriptors: MW 405.42, ALogP 5.46, HBA 5, HBD 1, PSA 56.27, QED 0.61
Compound (SMILES): COc1ccc(-c2cccc(S(=O)(=O)N[C@@H](Cc3cccc(C(=N)N)c3)C(=O)N3CCN(C(=O)C4CCCCC4)CC3)c2)c(OC)c1
InChIKey: LNNWDFRSVZFSAT-HKBQPEDESA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Binding affinity to FXa (unknown origin) using Mes-DArg-Pro-Arg-AMC as substrate
Measurement: Ki = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 661.83, ALogP 3.8, HBA 7, HBD 3, PSA 155.12, QED 0.21
Compound (SMILES): C=CC(=O)N1CCC[C@@H](NC(=O)c2sc3nccc4c3c2NC(=O)N4c2cnc(OC(C)C)cc2C)C1
InChIKey: KKABTGLLFMGRGR-MRXNPFEDSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Lanthascreen Binding Assay: A BTK kinase lanthascreen binding assay monitors compound binding to unphosphorylated-BTK kinase domain (UP-BTK), by competing with a fluorescent labeled tracer. UP-BTK, consisting of the kinase domain of non-phosphorylated BTK protein (389-659aa), was produced in a Baculovirus/insect cell expression system. Into a 384-well plate, 2 ng of GST-tagged human BTK (389-659aa) was incubated with compound, 50 nM of Tracer 236 and 2 nM anti-GST antibody for 60 minutes using an optimized Lanthascreen assay. After 60 minutes, plates were read at 340 nM and 615/665 nM in an Infinite F500 (Tecan).
Measurement: IC50 = 794 nM (pChEMBL 6.099999904632568)
Descriptors: MW 520.62, ALogP 4.38, HBA 7, HBD 2, PSA 116.76, QED 0.47
Compound (SMILES): C[N+]1(C)CCC(Oc2ccc(/C=C/c3ccccc3)cc2)CC1.[I-]
InChIKey: DZSIDBQMKNPWAK-HRNDJLQDSA-M
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]-epibatidine from human alpha4beta2 nAChR expressed in HEK293 cells membrane assessed as inhibition constant preincubated for 5 mins followed by overnight incubation with [3H]-epibatidine by gamma liquid scintilation counting analysis
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 308.45, ALogP 4.47, HBA 1, HBD 0, PSA 9.23, QED 0.6
Compound (SMILES): Nc1nc(C(=O)NCCc2ccccn2)cn2c1nc1ccccc12
InChIKey: MWISIRXEPKXITJ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at A2AAR in human HEK293 cells assessed as inhibition of CGS21680-induced cAMP production preincubated for 15 mins followed by CGS21680 addition and measured after 15 mins by HTRF assay
Measurement: IC50 = 646.8 nM (pChEMBL 6.190000057220459)
Descriptors: MW 332.37, ALogP 1.83, HBA 6, HBD 2, PSA 98.2, QED 0.59
Compound (SMILES): COc1cc(N2CCC3(CCN(C)CC3)CC2)c(Cl)cc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: OVLOWINKVPGUAP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) using biotinylated substrate incubated for 1 hr in the presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 603.54, ALogP 6.84, HBA 8, HBD 2, PSA 82.62, QED 0.28
Compound (SMILES): CCCCCCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(C)=C[C@@H]21
InChIKey: OJTMRZHYTZMJKX-RTBURBONSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Binding affinity to human CB2 receptor assessed as inhibition constant
Measurement: Ki = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 342.52, ALogP 6.52, HBA 2, HBD 1, PSA 29.46, QED 0.47
Compound (SMILES): CCOC(=O)C1=CN(C(=O)c2cc(OC)c(OC)c(OC)c2)C=C(C(=O)OCC)C1c1ccccc1
InChIKey: HNPBVHDWBCFNHZ-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Binding affinity to N-terminal his-tagged human SIRT5 (34 to 302 residues) expressed in Escherichia coli assessed as dissociation constant by microscale thermophoresis assay
Measurement: Kd = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 495.53, ALogP 3.85, HBA 8, HBD 0, PSA 100.6, QED 0.48
Compound (SMILES): N[C@H]1CC[C@H](NC2CC2c2ccc3c(c2)CCN3S(=O)(=O)c2ccccc2)CC1
InChIKey: AOKTYMNPAGJHMH-BWHLVSMOSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.57, ALogP 3.15, HBA 4, HBD 2, PSA 75.43, QED 0.79
Compound (SMILES): COC(=O)[C@H](Cc1ccc(O)cc1)NCC[C@@H](N)[C@H](O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)OC
InChIKey: COMBCDCRFAXRAT-QDXQZTBOSA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 639.75, ALogP 1.06, HBA 10, HBD 7, PSA 205.1, QED 0.1
Compound (SMILES): CC1(C)c2cc(OCCN3CCCOCC3)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCC4CC4)ccn3)ccc21
InChIKey: PJFDUIVXIFHGSE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 576.69, ALogP 5.99, HBA 7, HBD 0, PSA 74.03, QED 0.25
Compound (SMILES): Cc1ccccc1[C@@H]1NC(=O)[C@H](NC(=O)[C@@H](N)Cc2c(C)cc(O)cc2C)CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](c2ccccc2)NC1=O
InChIKey: RVFKLUAKDVBSKD-LNAXGRFASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Inhibition of Wistar rat brain membrane MOP
Measurement: IC50 = 1.09 nM (pChEMBL 8.960000038146973)
Descriptors: MW 713.84, ALogP 1.05, HBA 8, HBD 8, PSA 234.84, QED 0.18
Compound (SMILES): C=CC(=O)Nc1cn(C)nc1Nc1n[nH]c2ccc(O[C@H](C)c3c(Cl)cncc3Cl)cc12
InChIKey: CJSKEGHWGHQXBU-LLVKDONJSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 5 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 472.34, ALogP 5.01, HBA 7, HBD 3, PSA 109.75, QED 0.33
Compound (SMILES): CNC(=O)c1cc(Nc2ccccc2)cc(-c2ccnc(NC(=O)C3CCOCC3)c2)c1
InChIKey: VBODBJMAVPEPIF-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: O60331
Assay: Inhibition of PIP5Kgamma (unknown origin)
Measurement: IC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 430.51, ALogP 4.22, HBA 5, HBD 3, PSA 92.35, QED 0.54
Compound (SMILES): C[C@H](Oc1ccc2c(c1)OCCn1cc(-c3ncnn3CC(F)(F)F)nc1-2)C(N)=O
InChIKey: BLCVYWUNXXAHGY-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms by the Formula I compounds of Table 1. In addition, two clinically tested PI3K compounds, taselisib and pictilisib are included as comparators. The representative compounds of the invention exhibit strong activity against PI3Kα, and exhibit significantly enhanced selectivity relative to the other isoforms PI3Kβ, PI3Kδ, and PI3Kγ when compared to taselisib (GDC-0032) and pictilisib (GDC-0941). In particular, the selectivity ratios in the second from the right column of Table 2A show that each Formula I compounds 101-107 has a PI3K alpha to delta selectivity ratio far higher than taselisib or pictilisib. In fact, both taselisib and pictilisib have stronger activity against PI3K delta than against PI3K alpha, i.e. their selectivity ratios are less than 1. The selectivity ratios of Formula I compound 101-107 range from 301-fold to 634-fold.
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 422.37, ALogP 2.02, HBA 8, HBD 1, PSA 110.08, QED 0.67
Compound (SMILES): CC(C)(C)c1ccc(O[C@@H]2CCC[C@H]2Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1
InChIKey: UUKIPCRYYDMZJF-LVNUPDNPSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 483.57, ALogP 2.15, HBA 10, HBD 4, PSA 134.78, QED 0.42
Compound (SMILES): CN(C)C(=O)c1ccc2cccccc1-2
InChIKey: CJMSEGFRPRGPCU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 199.25, ALogP 2.49, HBA 1, HBD 0, PSA 20.31, QED 0.69