lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(N[C@@H](CO)c4ccccc4)n3)cc12
InChIKey: WQCXLUNOPQPYFK-IBGZPJMESA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: IC50 = 67.44 nM (pChEMBL 7.170000076293945)
Descriptors: MW 345.41, ALogP 3.47, HBA 5, HBD 3, PSA 86.72, QED 0.52
Compound (SMILES): O=c1c2cc(O)c(O)cc2oc2cc(O)c([C@H]3O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]3O)c(O)c12
InChIKey: AEDDIBAIWPIIBD-XQOGOWKJSA-N
Target: Maltase-glucoamylase (SINGLE PROTEIN), Homo sapiens
UniProt: O43451
Assay: Inhibition of alpha-glucosidase (unknown origin) using PNPG as substrate preincubated for 15 mins followed by substrate addition by spectrophotometric assay
Measurement: IC50 = 13300 nM (pChEMBL 4.880000114440918)
Descriptors: MW 422.34, ALogP -0.72, HBA 11, HBD 8, PSA 201.28, QED 0.19
Compound (SMILES): CC1(C)C[C@H](Nc2cc(NCc3cnccc3C(F)(F)F)ncc2C#N)CC(C)(C)[C@H]1O
InChIKey: JRKIWLCZVXSNKH-UKIBZPOASA-N
Target: Protein kinase C delta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q05655
Assay: Inhibition of PKA-delta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 447.51, ALogP 4.97, HBA 6, HBD 3, PSA 93.86, QED 0.6
Compound (SMILES): Cc1sc(C(=O)c2cncnc2N[C@@H]2C[C@H](COS(N)(=O)=O)[C@@H](O)C2)cc1C1OCCc2ccc(Cl)cc21
InChIKey: HKIARJIHQHADQP-MHPKPXDFSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBE0
Assay: Inhibition of recombinant SAE (unknown origin) assessed as reduction in transfer of SUMO1 to UBC9 using SUMO1 as a substrate in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 579.1, ALogP 3.16, HBA 10, HBD 3, PSA 153.73, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C(=O)NCc4ccccc4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: IRQCUSVEDQIEAO-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa2 cells assessed as reduction in lactate production incubated for 2 hrs by fluorescence based assay
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 663.73, ALogP 5.09, HBA 8, HBD 3, PSA 157.27, QED 0.18
Compound (SMILES): CC1(C)CCc2cc(F)ccc2N1Cc1ccc(C(=O)NO)cc1
InChIKey: ZBEQGZLGWWZPPB-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 328.39, ALogP 3.68, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): O=C1CCCc2c1cnn2-c1ccc(S(=O)(=O)Nc2ccc([N+](=O)[O-])cc2)cc1
InChIKey: QTBNOGKZOZCZBN-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 50300 nM (pChEMBL 4.300000190734863)
Descriptors: MW 412.43, ALogP 3.1, HBA 7, HBD 1, PSA 124.2, QED 0.51
Compound (SMILES): O=c1cc(-c2ccc(O)cc2)oc2c(CN3CCN(Cc4ccncc4)CC3)c(O)cc(O)c12
InChIKey: VVBZPBWLCKEFCR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of recombinant human full-length PARP-2 using biotinylated substrate
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 459.5, ALogP 3.29, HBA 8, HBD 3, PSA 110.27, QED 0.42
Compound (SMILES): COc1ccc2nc(NC(=O)c3[nH]c(C)c(Cl)c3Cl)sc2c1
InChIKey: KCNZLXDROLSJEU-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase assessed reduction in relaxation of supercoiled pNO1 DNA measured after 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 356.23, ALogP 4.5, HBA 4, HBD 2, PSA 67.01, QED 0.73
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NCc4cc5c(nn4)OCCO5)CO3)c2c1
InChIKey: DSAGBJCBALJSSU-WRPOGVCQSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus topoisomerase IV decatenation activity using kDNA as substrate by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 472.47, ALogP 1.38, HBA 10, HBD 2, PSA 117.08, QED 0.52
Compound (SMILES): CCc1cc(Nc2nc(NCc3ccc(F)cc3)nc3ccccc23)n[nH]1
InChIKey: MYVXPLSILQDDFA-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of N-terminal human TRKA (436 to 790 residues) expressed in baculovirus expression system using TK as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 362.41, ALogP 4.41, HBA 5, HBD 3, PSA 78.52, QED 0.47
Compound (SMILES): CC(=O)c1ccc(NCC(=O)NCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: QQFNWKWDDCPIJH-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins measured by stopped flow CO2 hydration assay
Measurement: Ki = 420.5 nM (pChEMBL 6.380000114440918)
Descriptors: MW 361.42, ALogP 1.26, HBA 5, HBD 3, PSA 118.36, QED 0.64
Compound (SMILES): CCCCCc1cccc(C(=O)Nc2c(O)c3ccc(O)cc3oc2=O)c1
InChIKey: MPWMECWSEIJTHJ-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ8
Assay: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3B by time-resolved FRET assay
Measurement: Ki = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 367.4, ALogP 4.19, HBA 5, HBD 3, PSA 99.77, QED 0.45
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3n[nH]c4c3CN(Cc3cccc(F)c3F)C4(C)C)cc2)CC1
InChIKey: VDWUFEKTWXEZTN-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of N-terminal GST-tagged human TRKB (456 to 822 residues) expressed in baculovirus infected Sf21 cells using TK as substrate in presence of ATP measured after 40 mins by HTRF assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 480.56, ALogP 3.94, HBA 5, HBD 2, PSA 67.5, QED 0.58
Compound (SMILES): CCOC(=O)c1cnc2c(NC(=O)NCc3ccc(S(N)(=O)=O)cc3)cnn2c1C
InChIKey: HVBAWGHCQIJWMH-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 by stopped-flow CO2 hydration assay
Measurement: Ki = 82.9 nM (pChEMBL 7.079999923706055)
Descriptors: MW 432.46, ALogP 1.18, HBA 8, HBD 3, PSA 157.78, QED 0.49
Compound (SMILES): Cc1cc(NC(=O)Oc2ccccc2)ccc1-c1cnc(N)c(C(=O)NC(C)C)c1
InChIKey: HZRVZTYGGHKYBH-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 2 subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05198
Assay: Inhibition of eIF2alpha (unknown origin) assessed as eIF2alpha phosphorylation by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 404.47, ALogP 4.39, HBA 5, HBD 3, PSA 106.34, QED 0.58
Compound (SMILES): CNCc1ccc(-c2ncc(OCC3CCNCC3)nc2-c2ccc(-c3ccoc3)cc2)cc1
InChIKey: DWLNIKROQOYAQD-UHFFFAOYSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Inhibition Zika virus NS3B (47 to 95 residues)/NS3 (1 to 170 residues) protease expressed in Escherichia coli BL21 using 7-amino-4-methylcoumarin as substrate by fluorescence assay
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 454.57, ALogP 5.17, HBA 6, HBD 2, PSA 72.21, QED 0.38
Compound (SMILES): CCNC(=O)c1cc(Cc2cccc3[nH]ccc23)nc(-c2cn(C)nn2)c1
InChIKey: MMMRGZLSUKMQOD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 360.42, ALogP 2.7, HBA 5, HBD 2, PSA 88.49, QED 0.57
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@@H]2C[C@@H](C(F)(F)F)CN2C(=O)[C@H](Cc2ccccc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2ccc(C(N)=O)cc2)NC(=O)[C@@H]2Cc3ccccc3CN2C(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCN)NC1=O
InChIKey: FENRDXNNEXLLLB-NZGSBNGHSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: O55239
Assay: Inhibition of mouse recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 1160.33
Compound (SMILES): CNc1nccc2c(Br)cc3cc(C(=O)[O-])ccc3c12.[Na+]
InChIKey: KRHIOCIKDYDRAO-UHFFFAOYSA-M
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of CSNK2A1(unknown origin) using Ser/Thr 11 as substrate incubated for 60 mins in presence of ATP by Z'-LYTE assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 331.17, ALogP 3.89, HBA 3, HBD 2, PSA 62.22, QED 0.7
Compound (SMILES): CC(C)[C@@H]1CNC(=N)N1C[C@@H]1CCCN1[C@@H](CC1CCCCC1)N1C[C@@H](C(C)C)N(CC23CC4CC(CC(C4)C2)C3)C1=N
InChIKey: ACHNGGZJHZFEDD-OZKQTGAYSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as stimulation of intracellular cAMP accumulation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 593.95, ALogP 6.41, HBA 3, HBD 3, PSA 72.69, QED 0.27
Compound (SMILES): C[C@H]1CN(C(=O)CCC2(C3CC3)NC(=O)NC2=O)CCN1c1cccc(Cl)c1
InChIKey: IABWDXKLHPEEBX-SZQRVLIRSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHI8
Assay: Inhibition of human recombinant ADAMTS-1 (AA253 to 734) assessed as cleavage of fluorescent substrate using 5(6)-fluorescein-NH-AELQGRPISIAK-5(6)-TAMRA as substrate incubated for 120 mins by biochemical assay
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 404.9, ALogP 2.15, HBA 4, HBD 2, PSA 81.75, QED 0.74
Compound (SMILES): CN(C)CCCC[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccccc2)N(C)C(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2ccc(C(N)=O)cc2)NC(=O)[C@@H]2Cc3ccccc3CN2C(=O)[C@@H]2CCCN2C1=O
InChIKey: IWBGAPDBWGYOFU-XKIFMCPMSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: O55239
Assay: Inhibition of mouse recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy
Measurement: IC50 = 1350 nM (pChEMBL 5.869999885559082)
Descriptors: MW 1184.43
Compound (SMILES): CNC(=O)c1cc(C(=O)NCCc2cnn(C)c2)cc2c1OC[C@H]2c1ccccc1
InChIKey: SAGHZUFIERAQOB-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 404.47, ALogP 2.28, HBA 5, HBD 2, PSA 85.25, QED 0.66
Compound (SMILES): COc1ccc(-c2cc3cc(C(=O)O)c(=O)oc3cc2O)cc1
InChIKey: HATVSSJNVYMOKP-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 312.28, ALogP 2.87, HBA 5, HBD 2, PSA 96.97, QED 0.72
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N1Cc2ccccc2C[C@@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: MZKBATMSEGBSAF-USSRGBPDSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing Galphai1 RlucII assessed as dissociation of Galphai1 from Gbetta/gamma subunit measured using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 1577.86
Compound (SMILES): N#Cc1ccc2c(c1)CCCCN2Cc1ccc(C(=O)NO)cc1
InChIKey: BCEXHGZSELIQJR-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using Ac-GAK(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 248 nM (pChEMBL 6.610000133514404)
Descriptors: MW 321.38, ALogP 3.02, HBA 4, HBD 2, PSA 76.36, QED 0.67
Compound (SMILES): Cc1cc2nc3n(c(=O)c2cc1NC(=O)c1cc2cc(F)ccc2[nH]1)CCC3
InChIKey: XJPSIHQTVULAQO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE by Ellman's method
Measurement: IC50 = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 376.39, ALogP 3.52, HBA 4, HBD 2, PSA 79.78, QED 0.56
Compound (SMILES): COc1cc2c(cc1OC)CN(CCNC(=O)c1ccc(C)c(Nc3nccc(-c4ccco4)n3)c1)CC2
InChIKey: NSYBFCBVMIYRAL-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp-mediated multidrug resistance in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity at 20 uM by measuring adriamycin IC50 after 48 hrs by MTT assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 513.6, ALogP 4.59, HBA 8, HBD 2, PSA 101.75, QED 0.34
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2)c(C(=O)N2CCSCC2)c1)[C@@H]1CCCN1c1nc(Nc2cc(F)cc(F)c2)ncc1Cl
InChIKey: XCRKAAJDBZMKHE-SANMLTNESA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of human ALK assessed as decreased enzymatic reactions measured after 1 hr by mobility shift assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 644.15, ALogP 4.78, HBA 9, HBD 2, PSA 102.93, QED 0.38
Compound (SMILES): Cc1ccsc1-c1nc(CNc2ccc(C(=O)NO)cc2)n(-c2ccccc2)n1
InChIKey: KTTQJBWGVWPYMZ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using Z-(Ac)-Lys-AMC as substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 405.48, ALogP 4.04, HBA 7, HBD 3, PSA 92.07, QED 0.33
Compound (SMILES): O=C1CC2(CC2)CN1c1cnc(NCc2c(F)ccc3c2CCO3)n2cnnc12
InChIKey: UWOLLTNLUAOGPM-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: Inhibition of EED in human G-401 cells assessed as reduction in H3K27 trimethylation incubated for 48 hrs by HTRF assay
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 394.41, ALogP 2.33, HBA 7, HBD 1, PSA 84.65, QED 0.73
Compound (SMILES): Fc1ccc2[nH]c(CNc3nc(N4CCOCC4)nc4c3ncn4-c3nccs3)nc2c1F
InChIKey: AWRYUTPYSORJOG-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of casein kinase 1epsilon (unknown origin)
Measurement: IC50 = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 469.48, ALogP 2.88, HBA 10, HBD 2, PSA 109.67, QED 0.4
Compound (SMILES): CC(CC1(C)NC(=O)NC1=O)C(=O)N1CCN(c2cc(Cl)cc(Cl)c2)CC1
InChIKey: KTSVBNSBXWVDTE-UHFFFAOYSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O75173
Assay: Inhibition of human recombinant ADAMTS-4 (AA1 to 520) assessed as cleavage of fluorescent substrate using as TBIS-1 substrate incubated for 180 mins by biochemical assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 413.31, ALogP 2.27, HBA 4, HBD 2, PSA 81.75, QED 0.74
Compound (SMILES): CCS(=O)(=O)c1ccc([C@@H](CC(=O)NC)C(=O)Nc2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)cc1
InChIKey: FQOWZQYVIFDJJK-QGZVFWFLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 540.48, ALogP 3.65, HBA 5, HBD 3, PSA 112.57, QED 0.44
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OCC(O)C(O)COc3cccc2c3)cc1OC
InChIKey: PBDSFPLSNACCRE-QQIJZFFGSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02790
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 795 nM (pChEMBL 6.099999904632568)
Descriptors: MW 761.91, ALogP 6.18, HBA 11, HBD 2, PSA 142.45, QED 0.25
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCN2CCCCCC2)CC(=O)O)nn1C1CCCC1.Cl
InChIKey: NRTHDBXOXIGPBR-BDQAORGHSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human AGTRL1 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 3752 nM (pChEMBL 5.429999828338623)
Descriptors: MW 512.65, ALogP 4.52, HBA 7, HBD 2, PSA 105.92, QED 0.46
Compound (SMILES): COc1cc(-n2nnc(S(=O)(=O)c3ccc(C(C)(C)C)cc3)c2C)c(OC)cc1Br
InChIKey: ACHYQRJTXWSXNR-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: EC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 494.41, ALogP 4.49, HBA 7, HBD 0, PSA 83.31, QED 0.52
Compound (SMILES): CC(=O)NC(C(=O)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1)c1ccc(S(C)(=O)=O)cc1
InChIKey: ODJIXKMFLJOGDA-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 512.43, ALogP 3.22, HBA 5, HBD 3, PSA 112.57, QED 0.51
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4c(c3N(C)C2=O)CC(=O)N4)c1F
InChIKey: YPQHVWLVVJREBV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 390.35, ALogP 2.45, HBA 5, HBD 1, PSA 84, QED 0.87
Compound (SMILES): O=C(OCN1C(=O)c2ccccc2S1(=O)=O)c1ccccc1Cl
InChIKey: SVFQFTUMOZPJGL-UHFFFAOYSA-N
Target: Presenilin-associated rhomboid-like protein, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H300
Assay: Inhibition of human PARL transfected in HEK293T cell membrane assessed as inhibition of FP-Rh labeling treated with compound for 30 mins prior to FP-Rh addition by competitive ABPP based analysis
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 351.77, ALogP 2.3, HBA 5, HBD 0, PSA 80.75, QED 0.79
Compound (SMILES): CC[C@@H]1C[C@H]1Nc1ncc2c(C3CCN(C(=O)c4cc(C)nc(C)c4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: RCQLJPMEVONOSW-ZCIWVVNKSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 516.69, ALogP 5.15, HBA 7, HBD 2, PSA 96.17, QED 0.47
Compound (SMILES): CCc1cc(Cl)c(OC)c(C(=O)NC[C@@H]2C[C@@H](OCCCCOCc3ccccc3)CN2)c1O
InChIKey: KRHWCJYTVWDZJO-LEWJYISDSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by MicroBeta scintillation counting method
Measurement: Ki = 1.01 nM (pChEMBL 9)
Descriptors: MW 491.03, ALogP 4.09, HBA 6, HBD 3, PSA 89.05, QED 0.37
Compound (SMILES): Cc1coc(-c2cn([C@@H]3O[C@H](COc4ccc5ccc(N6CCC6)nc5c4)[C@@H](O)[C@@H]3F)c3ncnc(N)c23)n1
InChIKey: LSEFEXOHUPJOTB-HTCVQUQYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3-mediated m6A methylation in human MOLM-3 cells assessed as reduction in mRNA level measured after 24 hrs by LC-MS/MS analysis
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 531.55, ALogP 3.41, HBA 11, HBD 2, PSA 137.58, QED 0.34
Compound (SMILES): C/C(=C\CC/C(C)=C/CC[C@]1(C)CCc2cc(OC(=O)CCC(=O)O)cc(C)c2O1)CCC=C(CO)CO
InChIKey: DVRUOAVGSNCOLY-BZWLWALNSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX in human PMNL assessed as reduction in 5-LOX product formation preincubated for 10 mins before addition of AA and A23187 and measured after 10 mins by RP-HPLC method
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 528.69, ALogP 5.99, HBA 6, HBD 3, PSA 113.29, QED 0.15
Compound (SMILES): O=C(CCCCCCCCCCCCCCC(=O)NCCCCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43)NCCCCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43
InChIKey: GRBNASMXJRDFTF-GPQRCDDOSA-N
Target: Glycine receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23415
Assay: Antagonist activity at human glycine receptor subunit alpha-1 expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 1147.52
Compound (SMILES): COc1cc2ncnc(Oc3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)c2cc1OC
InChIKey: VRKCCBOVUKMTIE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of GST-6His tagged VEGFR2 (unknown origin) using biotin-aminohexyl-EEEEYFELVAKKKK-NH2 peptide substrate incubated for 90 mins by HTRF assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 484.43, ALogP 6.1, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)N/N=C\c3ccc(F)cc3)cc2-c2cccs2)cc1
InChIKey: OJWKGZPEBANNPS-CFRMEGHHSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 469.52, ALogP 3.15, HBA 7, HBD 2, PSA 119.44, QED 0.33
Compound (SMILES): CNC(=O)c1nc(-c2ccc(Cl)c(S(=O)(=O)Nc3ccc(F)c(F)c3)c2)cnc1N
InChIKey: AQBPBCWVAXDEAL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate incubated for 30 to 60 mins in presence of ATP by Kinase Glo luminescence kinase assay
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 453.86, ALogP 2.82, HBA 6, HBD 3, PSA 127.07, QED 0.54
Compound (SMILES): Cc1cccc(CNCCOc2cccc3c2ccn3Cc2ccccc2)c1
InChIKey: FIOBTXCHUKCEGJ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate preincubated with enzyme for 5 mins followed by substrate addition for 5 mins by Ellman's method
Measurement: IC50 = 957.5 nM (pChEMBL 6.019999980926514)
Descriptors: MW 370.5, ALogP 5.17, HBA 3, HBD 1, PSA 26.19, QED 0.43
Compound (SMILES): CC(C)(C)NC(=O)C1(N2CCCC2=O)C(=O)Nc2ccc([N+](=O)[O-])cc21
InChIKey: SYZWJJFNKUFZDM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine iodide as a substrate measured for 125 secs by DNTB reagent based Ellman's method
Measurement: IC50 = 94000 nM (pChEMBL 4.03000020980835)
Descriptors: MW 360.37, ALogP 1.28, HBA 5, HBD 2, PSA 121.65, QED 0.48
Compound (SMILES): CCN(CCCOc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1)Cc1ccc(N(C)C)cc1
InChIKey: JUAMMZGBBGJIKS-XDHOZWIPSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of rat cortex homogenate acetylcholinesterase by Ellman's method
Measurement: IC50 = 2470 nM (pChEMBL 5.610000133514404)
Descriptors: MW 501.67, ALogP 5.71, HBA 6, HBD 1, PSA 56.25, QED 0.18
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3ccc(C(=O)NCCC(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: MOSDWLNSTVBDPJ-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase assessed reduction in relaxation of supercoiled pNO1 DNA measured after 30 mins by fluorescence assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 441.3, ALogP 3.7, HBA 5, HBD 4, PSA 124.18, QED 0.46
Compound (SMILES): COc1ccc(-n2ncc3c2C=C2CCC[C@H]([C@@H](O)c4cc(F)c(F)c(OC)c4)C2C3)cc1
InChIKey: QAGAGBQKNPFAEQ-ZYOOMIPPSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P06536
Assay: Agonist activity at glucocorticoid receptor in rat INS-1 832/13 cells transfected with 3XGRE-promoter luciferase plasmid construct assessed as induction of receptor transactivation by luciferase reporter gene assay
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 452.5, ALogP 5.26, HBA 5, HBD 1, PSA 56.51, QED 0.57
Compound (SMILES): Cc1cc(OCc2cn(-c3ccc(S(N)(=O)=O)cc3)nn2)nc(N2CCN(c3ccc(F)cc3)CC2)n1
InChIKey: SXWAEKQQXUUNDG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 measured by stopped flow CO2 hydrase assay
Measurement: Ki = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 524.58, ALogP 2.06, HBA 10, HBD 1, PSA 132.36, QED 0.39
Compound (SMILES): COc1nn(C)cc1C(=O)Nc1cccc(-c2nncn2C(C)C(F)(F)F)n1
InChIKey: VOAVBNDXAXMDDN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of full-length human ASK1 expressed in HEK293T cells assessed as reduction in autophosphorylation of ASK1 at T383 residue incubated for 1 hr
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 395.35, ALogP 2.46, HBA 8, HBD 1, PSA 99.75, QED 0.71
Compound (SMILES): CC(C)(O)c1cccc(-n2cc(F)c3cnc(Nc4ccc(N5C[C@@H]6C[C@H]5CN6)cc4)nc32)n1
InChIKey: NMIWWLZKGDETAG-WMZOPIPTSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human WEE1 using LSNLYHQGKFLQTFCGSPLYRRR peptide as substrate incubated for 40 mins in presence of [gamma-33P]ATP by scintillation counting method
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 459.53, ALogP 3.48, HBA 8, HBD 3, PSA 91.13, QED 0.42
Compound (SMILES): COc1ncc(N2CCOCC2)cc1S(=O)(=O)Nc1cncc(C#CCN2CCN(C(C)C)CC2)c1
InChIKey: YUHCJHVTKGYFCP-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal His6-tagged full length P110alpha/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 514.65, ALogP 1.5, HBA 9, HBD 1, PSA 100.13, QED 0.55
Compound (SMILES): COc1ccc(-c2ccc(C(=O)N(CC(=O)NC3(C#N)CC3)Cc3ccccc3)cc2)cc1
InChIKey: TYMYINLXOFGBOV-UHFFFAOYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of recombinant human liver CatK using Z-FR-AMC as substrate by fluorescence assay
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 439.52, ALogP 4.18, HBA 4, HBD 1, PSA 82.43, QED 0.57
Compound (SMILES): CCc1cc2cnc(CN3CCN(c4ccc(C(=O)NC)nc4Cl)CC3)cc2[nH]c1=O
InChIKey: HBQCPOVYLRNWOU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Fluorescence Anisotropy Binding Assay: PARP2: Recombinant full length PARP2 protein was diluted to 6 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 2 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 440.94, ALogP 2.22, HBA 6, HBD 2, PSA 94.22, QED 0.59
Compound (SMILES): O=C(c1cccc(F)c1F)C1CCN(Cc2c(O)cc(O)c3c(=O)cc(-c4ccc(O)cc4)oc23)CC1
InChIKey: KYAONXACBFSKCA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of recombinant human full-length PARP-2 using biotinylated substrate
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 507.49, ALogP 4.95, HBA 7, HBD 3, PSA 111.21, QED 0.33
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H](Cc1cccc2ccccc12)C(=O)N1Cc2ccccc2C(C)(C)C1C(=O)O
InChIKey: FEAFTRZRTKRVPQ-BZUDJUENSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing Galphai1 RlucII assessed as dissociation of Galphai1 from Gbetta/gamma subunit measured using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 1655.97
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@H](c2cccc(C)n2)CC1
InChIKey: HOTAARNYDWLVIM-MBOZVWFJSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 370.92, ALogP 5.53, HBA 2, HBD 1, PSA 41.99, QED 0.75
Compound (SMILES): COc1cncc2c1[C@]1(O)[C@@H](CNC3COC3)[C@H](CO)[C@@H](c3ccccc3)[C@]1(c1ccc(Br)cc1)O2
InChIKey: XEZAMGVLOVUUBG-MSRUBZGQSA-N
Target: Eukaryotic initiation factor 4A-I (SINGLE PROTEIN), Homo sapiens
UniProt: P60842
Assay: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring short 5'-UTR of tubulin
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 553.45, ALogP 3.34, HBA 7, HBD 3, PSA 93.07, QED 0.41
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3C[C@@H](O)C[C@@H]32)cc(C(OC)c2ccccc2)n1
InChIKey: NXUPKMOZLDSAOF-BFPHGVDSSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-Thr tagged BRD4 BD2/BD1 Y97A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 395.46, ALogP 1.68, HBA 5, HBD 3, PSA 100.55, QED 0.69
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(CC1(F)CCN(Cc3cc(F)c(F)cc3F)CC1)C2
InChIKey: SYCRRTXHUITUKR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Binding affinity to CM5 sensor chip immobilized recombinant human AChE assessed as dissociation constant at 298.15 K by surface plasmon resonance assay
Measurement: Kd = 5.23 nM (pChEMBL 8.279999732971191)
Descriptors: MW 451.46, ALogP 4.87, HBA 4, HBD 0, PSA 38.77, QED 0.46
Compound (SMILES): Cc1nccc2c1c(=O)n(C)c1cc(OC[C@@H](N)CC(C)C)c(C#N)cc21
InChIKey: NQXBZPJVVGIFBJ-HNNXBMFYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of recombinant AAK1 (unknown origin) expressed in baculovirus assessed as reduction in AP-2 phosphorylation
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 364.45, ALogP 3.02, HBA 6, HBD 1, PSA 93.93, QED 0.7
Compound (SMILES): Cc1nc2c([C@H](C)c3ccc(C(F)(F)F)cc3)nn(CC(F)(F)F)c2c(=O)[nH]1
InChIKey: HGLBARWKJIABCX-MRVPVSSYSA-N
Target: GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (SINGLE PROTEIN), Macaca mulatta
UniProt: B3VTJ2
Assay: PDE2 Inhibition Assay: In a typical experiment the PDE2 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. Rhesus PDE2A3 was amplified from rhesus macaque brain cDNA (Biochain Institute, Hayward, Calif.) using primers based on human PDE2A sequence (accession NM_002599.3) where the forward primer containing a Kozak consensus was 5′-gccaccatggggcaggcatgtggc-3′ and the reverse primer was 5′-tcactcagcatcaaggctgca-3′. Amplification with Easy-A High-Fidelity PCR cloning enzyme (Stratagene, La Jolla, Calif.) was 95° C. for 2 minutes followed by thirty three cycles of 95° C. for 40 seconds, 52° C. for 30 seconds, and 72° C. for 2 minutes 48 seconds. Final extension was 72° C. for 7 minutes. The PCR product was TA cloned into pcDNA3.3-TOPO (Invitrogen, Carlsbad, Calif.) according to standard protocol. A consensus sequence was developed from multiple clones and then deposited into GenBank (EU812167). AD293 cells (Stratagene, La Jolla, Calif.) with 70-80% confluency were transiently transfected with rhesus PDE2A3/pcDNA3.3-TOPO using Lipofectamine 2000 according to manufacturer specifications (Invitrogen, Carlsbad, Calif.). Cells were harvested 48 hours post-transfection and lysed by sonication (setting 3, 10×5 sec pulses) in a buffer containing 20 mM HEPES pH 7.4, 1 mM EDTA and Complete Protease Inhibitor Cocktail Tablets (Roche, Indianapolis, Ind.). Lysate was collected by centrifugation at 75,000×g for 20 minutes at 4° C. and supernatant utilized for evaluation of PDE2 activity. The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP® FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product # R8139). IMAP® technology has been applied previously to examine the effects of phosphodiesterase inhibitors (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). Assays were performed at room temperature in 384-well microtiter plates with an incubation volume of 20.2 μL. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 8 μL of each of 10 solutions differing by 3-fold in concentration, at 32 serial dilutions per plate. 100% inhibition is determined using a known PDE2 inhibitor, which can be any compound that is present at 5,000 times its Ki value in the assay described below, such as Bay 60-7550 (Ki-0.2 nM) at 1 μM concentration for 100% inhibition. Bay 60-7550 was obtained from Axxora via Fisher Scientific (cat# ALX-270-421-M025/cat#NC9314773). Put another way, any compound with Ki of 0.2 to about 2 nM could be used at 1 to 10 μM. 0% of inhibition is determined by using DMSO (1% final concentrations).
Measurement: Ki = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 404.31, ALogP 4.16, HBA 4, HBD 1, PSA 63.57, QED 0.67
Compound (SMILES): Cc1ccc(-c2nc(CCc3ccccc3)c(-c3cccc(F)c3O)nc2C)s1
InChIKey: YCTSZTFLLOJXER-UHFFFAOYSA-N
Target: Extracellular calcium-sensing receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41180
Assay: Antagonist activity at human CaSR in human HEK293 cells measured after 5 mins by FLIPR assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 404.51, ALogP 6.12, HBA 4, HBD 1, PSA 46.01, QED 0.44
Compound (SMILES): NNC(=O)c1ncccn1
InChIKey: DQEIYNHQKWEZKR-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: P2X7 FLIPR Assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 138.13, ALogP -0.92, HBA 4, HBD 2, PSA 80.9, QED 0.3
Compound (SMILES): CCc1cccc2c1NC(=O)C2(C)C
InChIKey: MUSZGKUYZIXGPM-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16654
Assay: Inhibition of human PDHK4 co-complexed with porcine PDH using sodium pyruvate, coenzymeA and NAD as substrate preincubated with enzyme complex for 45 mins followed by ATP addition and then later incubated with substrate for 90 mins by absorption spectrophotometric assay
Measurement: IC50 > 300000 nM (pChEMBL 3.5230000019073486)
Descriptors: MW 189.26, ALogP 2.48, HBA 1, HBD 1, PSA 29.1, QED 0.72
Compound (SMILES): COc1cc(F)ccc1Nc1ncnc2ccc(-c3ccc(C(=O)N4CCNCC4)cc3)nc12
InChIKey: LEAJNJJPWHYFJT-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of MKN2 (unknown origin) in presence of ATP by HTRF assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 458.5, ALogP 3.63, HBA 7, HBD 2, PSA 92.27, QED 0.47
Compound (SMILES): COc1ccccc1C1=C(Nc2cccc(SC)c2)C(=O)NC1=O
InChIKey: JVTLNYITMMFMKI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O94804
Assay: Binding affinity human STK10 by binding displacement assay
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 340.4, ALogP 2.9, HBA 5, HBD 2, PSA 67.43, QED 0.65
Compound (SMILES): COc1ccc(C(=O)NCc2ccccc2CN2CCc3cc(OC)c(O)cc3C2)cc1
InChIKey: QRRPJFYRWJVNBL-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylspiperone from dopamine D3 receptor (unknown origin)
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 432.52, ALogP 3.9, HBA 5, HBD 2, PSA 71.03, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2cn(-c3nc(C(=O)O)cs3)nc2-c2cccc(OCc3ccccn3)c2)cc1
InChIKey: FDUIVDAUBFHRSL-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa2 cells assessed as reduction in lactate production incubated for 2 hrs by fluorescence based assay
Measurement: IC50 > 57000 nM (pChEMBL 4.24399995803833)
Descriptors: MW 547.62, ALogP 3.91, HBA 9, HBD 2, PSA 150.29, QED 0.28
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NC(=O)c6ccc(C)c(C)c6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: IJRXIXBRJVMCAQ-HDULXAKOSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat delta opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 1366 nM (pChEMBL 5.869999885559082)
Descriptors: MW 604.79, ALogP 6.96, HBA 5, HBD 1, PSA 60.03, QED 0.32
Compound (SMILES): CNc1cccc([C@H]2C[C@@]34CC[C@]2(OC)[C@@H]2Oc5c(OC)ccc6c5[C@@]23CCN(CC2CC2)[C@@H]4C6)c1
InChIKey: SPKWQLCFAVQULT-VTPACTEHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat delta opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 178.7 nM (pChEMBL 6.75)
Descriptors: MW 486.66, ALogP 5.13, HBA 5, HBD 1, PSA 42.96, QED 0.61
Compound (SMILES): CCC[C@]1(CO)NC[C@H](O)[C@@H](O)[C@@H]1O.Cl
InChIKey: ZCAWNKJDQGBCBS-NPPHLGRCSA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal isomaltase using p-nitrophenyl glycoside as substrate assessed as release of p-nitrophenol measured by spectrometric assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 205.25, ALogP -1.8, HBA 5, HBD 5, PSA 92.95, QED 0.37
Compound (SMILES): COc1cc2c(cc1OCC(F)(F)F)CCN1CC(CC(C)C)C(O)CC21
InChIKey: JXFGMMABBUBPCW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 6510 nM (pChEMBL 5.190000057220459)
Descriptors: MW 387.44, ALogP 3.96, HBA 4, HBD 1, PSA 41.93, QED 0.83
Compound (SMILES): COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)CP(=O)(O)[C@@H](N)CCc1ccccc1
InChIKey: QWLYILUODIZPOK-ZSQFBXSQSA-N
Target: Endoplasmic reticulum aminopeptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZ08
Assay: Inhibition of ERAP1 (unknown origin) using L-AMC as substrate
Measurement: IC50 = 141.25 nM (pChEMBL 6.849999904632568)
Descriptors: MW 527.6, ALogP 4.22, HBA 5, HBD 4, PSA 134.51, QED 0.19
Compound (SMILES): O=S(=O)(Nc1cccc(F)n1)c1cc(F)c(O[C@H]2CCN(CC(F)(F)F)C[C@@H]2c2ccc(F)c(F)c2)c(F)c1
InChIKey: ALYSSPGOUMAGSF-QRWLVFNGSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 by automated voltage clamp electrophysiology
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 581.49, ALogP 5.38, HBA 5, HBD 1, PSA 71.53, QED 0.3
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](NC(=O)c3cncc(F)c3)C[C@@H]21
InChIKey: JYDAEHNHBJFJRG-WPXMVPHTSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse Panc02 cells incubated for 48 hrs by RFMS method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 415.9, ALogP 3.84, HBA 3, HBD 2, PSA 71.09, QED 0.75
Compound (SMILES): O=C(NO)c1ccc(CN2C(=O)CN(Cc3ccc(Cl)cc3)C2=O)cc1
InChIKey: IFUKDPGEHLTXFM-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using Ac-LeuGlyLys(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and further incubated for incubated for 1 hrs by fluorescence microtiter plate reader assay
Measurement: IC50 = 1082 nM (pChEMBL 5.96999979019165)
Descriptors: MW 373.8, ALogP 2.42, HBA 4, HBD 2, PSA 89.95, QED 0.48
Compound (SMILES): Cc1c(Cc2ccccc2)c(-c2cc(Cl)nc(N)n2)nn1C
InChIKey: VSMTYSWGHKYXOF-UHFFFAOYSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Inhibition of human ADCY10
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 313.79, ALogP 3.01, HBA 5, HBD 1, PSA 69.62, QED 0.75
Compound (SMILES): COc1cc2nc(-c3ccc(C)o3)nc(NCC3CCN(c4ncc(C(=O)NO)cn4)CC3)c2cc1OC
InChIKey: CIGOMCAFKVJNOA-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of full length human C-terminal His-tagged HDAC3/human N-terminal GST-agged NCOR2 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 519.56, ALogP 3.45, HBA 11, HBD 3, PSA 147.76, QED 0.23
Compound (SMILES): C/C(=N/NC(=O)c1ccc(S(N)(=O)=O)cc1)c1ccc(Br)cc1
InChIKey: NXBPMCGIKFKXCR-ZDLGFXPLSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 by stopped-flow CO2 hydration assay
Measurement: Ki = 7991 nM (pChEMBL 5.099999904632568)
Descriptors: MW 396.27, ALogP 2.25, HBA 4, HBD 2, PSA 101.62, QED 0.61