lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1CN(CC[C@H]2CC[C@H](NC(=O)c3ccco3)CC2)CCc2ccc(Cl)cc21
InChIKey: KHPOIBBWMVNTMI-WFXMLNOXSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from recombinant human D2L receptor expressed in CHO cells
Measurement: Ki = 93.9 nM (pChEMBL 7.03000020980835)
Descriptors: MW 414.98, ALogP 5.27, HBA 3, HBD 1, PSA 45.48, QED 0.72
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(S(N)(=O)=O)cc2)c1C
InChIKey: FQHFSRHRIAXUPP-WYMPLXKRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 7893 nM (pChEMBL 5.099999904632568)
Descriptors: MW 488, ALogP 3.84, HBA 9, HBD 2, PSA 128.15, QED 0.31
Compound (SMILES): O=C(Nc1cccnn1)N1CC(C/C=C/c2cncc(Oc3ccc(C(F)(F)F)cn3)n2)C1
InChIKey: WBFGOFIEIRLCBO-DAFODLJHSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000540a GABRA1
Measurement: Ki = 1140 nM (pChEMBL 5.940000057220459)
Descriptors: MW 457.42, ALogP 4.04, HBA 7, HBD 1, PSA 106.02, QED 0.6
Compound (SMILES): O=C(O)c1cccc2c1NC(c1ccc(F)cc1)C1CC(Sc3ccccc3[N+](=O)[O-])C(Cl)C21
InChIKey: PFNDLHUUVRPUCP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin)
Measurement: IC50 = 67600 nM (pChEMBL 4.170000076293945)
Descriptors: MW 498.96, ALogP 6.47, HBA 5, HBD 2, PSA 92.47, QED 0.24
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3ccc(N)nc3)cc1N(c1ccc(Cl)cc1)C[C@H]2C
InChIKey: SBRJLPKKZHHGCO-CQSZACIVSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD1 (unknown origin) using biotinylated JQ1 analog as substrate measured after 20 mins by AlphaLISA assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 416.92, ALogP 5.13, HBA 6, HBD 1, PSA 72.86, QED 0.49
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(F)cc3F)s2)cc1
InChIKey: ZYPBPRUPMVUKSS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 450.47, ALogP 5.58, HBA 5, HBD 1, PSA 68.29, QED 0.39
Compound (SMILES): Cn1cncc1-c1ccc2cnc(NC(=O)c3ccnc(N4CC(N)C4)c3)cc2c1
InChIKey: NQRNCMCZKKSTEC-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 399.46, ALogP 2.43, HBA 7, HBD 2, PSA 101.96, QED 0.55
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(c2cc(-c3ccccc3O)nnc2N)CC1
InChIKey: AQTNUGRRZDRZIA-UHFFFAOYSA-N
Target: Protein polybromo-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U86
Assay: Binding affinity to polybromo-1 (3) (unknown origin) by ITC analysis
Measurement: Kd = 1963 nM (pChEMBL 5.710000038146973)
Descriptors: MW 371.44, ALogP 2.49, HBA 7, HBD 2, PSA 104.81, QED 0.84
Compound (SMILES): O=C1c2cccc(F)c2C(=O)C1(O)O
InChIKey: ZYOWGKVMQVHSGM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 44300 nM (pChEMBL 4.349999904632568)
Descriptors: MW 196.13, ALogP -0.11, HBA 4, HBD 2, PSA 74.6, QED 0.45
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@H](O)c3ccc(-c4ccc(C#N)cc4)cc3F)n2)cc1
InChIKey: RSDODWDGOTXMEA-XMMPIXPASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 163.7 nM (pChEMBL 6.789999961853027)
Descriptors: MW 421.44, ALogP 4.85, HBA 6, HBD 2, PSA 105.62, QED 0.48
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(C)c3ccccc34)cc2)cc1
InChIKey: QRCCYPSGLCYDNW-NDEPHWFRSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 508.66, ALogP 5.83, HBA 4, HBD 1, PSA 53.01, QED 0.39
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cc1c(Nc2ccc(S(=O)(=O)N3CCN(C)CC3)cc2F)nc2ccc(-c3cnn(C4CC4)c3)cn2c1=O
InChIKey: JYTISQGEFSHUIR-UHFFFAOYSA-N
Target: Nucleosome-remodeling factor subunit BPTF (SINGLE PROTEIN), Homo sapiens
UniProt: Q12830
Assay: Selectivity interaction (AlphaScreen) EUB0000253b BPTF
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 537.62, ALogP 3.02, HBA 9, HBD 1, PSA 104.84, QED 0.4
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CCN)C(=O)NCc1ccccc1Cl)c1sccc1C
InChIKey: QKKGISPNJFYJKR-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 502.15, ALogP 5.87, HBA 5, HBD 2, PSA 58.36, QED 0.35
Compound (SMILES): FCCCN1CC(Nc2ccc([C@@H]3c4ccc5[nH]ncc5c4C[C@@H](C(F)F)N3CC(F)F)nc2)C1
InChIKey: FWWHNGKEZAFESY-GMAHTHKFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Binding Assay: hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials [Sanguinetti et al., Nature, 2006, 440, 463-469.] and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 494.51, ALogP 4.26, HBA 5, HBD 2, PSA 60.08, QED 0.44
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: AYKSFHQCPBPUPW-QFIPXVFZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 472.55, ALogP 1.14, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): CC(=O)N1CCC2(CC1)c1cc(C(=O)NCc3ccccc3Cl)ccc1N(S(=O)(=O)c1ccc(F)cc1)C2C
InChIKey: MOEVGYNBSQJEFD-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 570.09, ALogP 4.89, HBA 4, HBD 1, PSA 86.79, QED 0.47
Compound (SMILES): Cc1nc(OCc2ccc(F)cc2)c(C(=O)NC2CCCCCC2)cc1Br
InChIKey: LEHIEWISZPIBHW-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.34, ALogP 5.32, HBA 3, HBD 1, PSA 51.22, QED 0.65
Compound (SMILES): Nc1nn2c(-c3ccc(Br)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: VPJWECUQRFSGFO-WCWDXBQESA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 472.33, ALogP 3.8, HBA 8, HBD 2, PSA 141.09, QED 0.43
Compound (SMILES): O=C1c2nc3ccccc3n2CCN1CCCCOc1ccc(OC(F)(F)F)cc1
InChIKey: QRCUMXUPIXTGPF-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.4, ALogP 4.25, HBA 5, HBD 0, PSA 56.59, QED 0.54
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(-c4nc(C56CCN(CC5)CC6)no4)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: RVFYCRCCTDEQQD-XMMPIXPASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 567.65, ALogP 4.56, HBA 11, HBD 3, PSA 138.53, QED 0.26
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4cnc5ccccc5c4)cc3c2)cn1
InChIKey: GUGOTVDQIVQZBF-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologies-a Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% Control") and phosphorylated ("100% control") forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 379.42, ALogP 4.44, HBA 5, HBD 1, PSA 72.7, QED 0.5
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1ccc(F)cc1
InChIKey: HJFHBVCVDRZKOR-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 57.3 nM (pChEMBL 7.239999771118164)
Descriptors: MW 391.39, ALogP 3.72, HBA 7, HBD 2, PSA 105.44, QED 0.55
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-DOQBYECHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 5.46 nM (pChEMBL 8.260000228881836)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4)ccn2)C1
InChIKey: ASEPZBUAEOJUCM-DLBZAZTESA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 activation measured after 6 hrs followed by Caspase-glo reagent based assay
Measurement: EC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 381.48, ALogP 2.91, HBA 5, HBD 2, PSA 88.91, QED 0.85
Compound (SMILES): C=CC(=O)Nc1ccc(-c2ccnc(Nc3cnn(CCOC)c3)n2)cc1
InChIKey: CKHJIDHRSXTJER-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 cytoplasmic domain (866 to 1154 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 1562 nM (pChEMBL 5.809999942779541)
Descriptors: MW 364.41, ALogP 2.85, HBA 7, HBD 2, PSA 93.96, QED 0.6
Compound (SMILES): CC[C@H](N[C@@H]1CC[C@@]2(OC)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3C)[C@H]1O5)C(=O)O
InChIKey: FGPMICJYDSZBIT-AXENNSGJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 2.22 nM (pChEMBL 8.649999618530273)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.69
Compound (SMILES): CC(C)(CO)NC(=O)c1cc(C(C)(C)C)n(-c2ccc(C(F)(F)F)cn2)n1
InChIKey: IIANDZHTDXIIKC-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in HEK293 cells after 24 hrs by luciferase reporter gene assay based Tango beta-arrestin recruitment method
Measurement: EC50 = 561.6 nM (pChEMBL 6.25)
Descriptors: MW 384.4, ALogP 3.08, HBA 5, HBD 2, PSA 80.04, QED 0.85
Compound (SMILES): Nc1nc(-c2ccccc2O)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: HMTBCEGHBBCZMF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 319.32, ALogP 1.83, HBA 7, HBD 2, PSA 98.44, QED 0.59
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2nc(-c3ncccc3F)ccc2N)C[C@@H](O)[C@]1(C)O
InChIKey: QVCLVTVRXGXXOR-FTMGGNRSSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 451.5, ALogP 3.14, HBA 7, HBD 4, PSA 134.25, QED 0.48
Compound (SMILES): C=CCOc1ccc2oc(CC)cc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: UXEFZEYHZIIDPC-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C INI receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 271.36, ALogP 3.62, HBA 3, HBD 1, PSA 48.39, QED 0.82
Compound (SMILES): COc1cc(OC)c2c(N3CCN(C)CC3)nc(-c3cc(C)c(OCCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: NTUCJWZWDDQYER-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full-length C-terminal His-tagged HDAC8 expressed in baculovirus infected Sf9 insect cells using Ac-Leu-Gly-Lys(Tfa)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 = 378.2 nM (pChEMBL 6.420000076293945)
Descriptors: MW 537.66, ALogP 4.13, HBA 9, HBD 2, PSA 109.28, QED 0.21
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1[nH]c(-c2ccc(F)cc2)nc1C(N)=O
InChIKey: QXMVYSCRIRLZNR-IBGZPJMESA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 457.55, ALogP 2.96, HBA 5, HBD 3, PSA 121.18, QED 0.42
Compound (SMILES): C=CC(=O)N1CCC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: DNWIBFXHQBOSSU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using ULight - 4E - BP1( Thr37 / Thr46 ) as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 391.48, ALogP 3.23, HBA 4, HBD 2, PSA 90.98, QED 0.74
Compound (SMILES): CC(=O)NCCC(C(=O)NCc1ccccc1Cl)N(C)CCC=C(c1sccc1C)c1sccc1C
InChIKey: BYIMWNNOGMXRCA-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse GAT2 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 4466.84 nM (pChEMBL 5.349999904632568)
Descriptors: MW 544.19, ALogP 6.04, HBA 5, HBD 2, PSA 61.44, QED 0.29
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(C(=O)O)cc1
InChIKey: GTVGUYLLAFHOLS-SRZZPIQSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 2254 nM (pChEMBL 5.650000095367432)
Descriptors: MW 388.39, ALogP 2.93, HBA 8, HBD 2, PSA 118.42, QED 0.31
Compound (SMILES): COc1cc2nccc(Oc3ccc(Nc4nccc5[nH]cc(-c6ccc(F)cc6)c(=O)c45)cc3F)c2cc1OC
InChIKey: SLRINRCTDNIRFQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: A study on inhibition of protein kinases activity at in vitro biochemical levelMaterial and method: kinases such as c-Met, VEGFR-2, Axl and RET, obtained from Invitrogen; HTRF KinEASE; TK kit (Cisbio Company); 384-well plate (Greiner Company); ATP (Sigma Company), MgCl2 (Sigma Company); PHERAstar FS multifunctional plate reader (BMG Company); conventional centrifuge (StaiteXiangyi Company); incubator (Binder Company). Dilution and storage of compounds: depending on solubility, the test compounds are prepared as stock solutions of 0.5-10 mmol/L with dimethyl sulphoxide (DMSO), and aliquots of the stock are stored at −20° C.;Preparation of working solution of the compounds: Before test, aliquots of the compounds are removed from the refrigerator, and diluted with pure DMSO to 50× of the level needed; and then the compounds are diluted with deionized water to 4× of the level needed;Preparation of 1.33× enzymatic buffer: 5× enzymatic buffer (from HTRF kit) is diluted to 1.33× with deionized water, and appropriate components of the final level 1.33× are added: 1.33 mmol/L dithiothreitol (DTT) and 1.33 mmol/L MgCl2;Preparation of kinase working solution: Met is diluted to 2× final level required, 0.2 ng/μL, with 1.33× enzymatic buffer;Preparation of substrate working solution: the substrate labeled with biotin (from HTRF kit) and ATP (10 mM) are diluted with 1.33× enzymatic buffer to prepare a mixture at 4× of the final level required;Preparation of the testing working solution: Streptavidin-XL665, 16.67 μmol/L is diluted with HTRF test buffer to 4× of the final level required, and then mixed with antibody-Cryptate of the same volume (both from the HTRF kit).Enzymatic reaction step: 4 μl of kinase working solution is added to each well of the low volume 384-well plate. Meanwhile, 4 μL 1.33× enzymatic buffer is added as the negative control. 2 μL compound working solution is added into each well, and 2 μL 8% DMSO in water is added as zero compound level control (i.e., positive control). At 25° C. (or 30 C), incubate for 5-10 min; add 2 μL substrate working solution into each well to initiate the enzymatic reaction. Allow to react while shaking at 25° C. (or 30° C.) for 15-60 min.
Measurement: IC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 552.54, ALogP 6.97, HBA 7, HBD 2, PSA 98.36, QED 0.22
Compound (SMILES): C[C@](O)(Cn1cc(F)cn1)C(=O)Nc1cnc(C#N)c(C(F)(F)F)c1
InChIKey: PLYZMJXXOPVZLJ-ZDUSSCGKSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Human Androgen Receptor (hAR) Ligand Binding Domain (LBD) Affinity Assay: Methods: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone.Increasing concentrations of SARDs or DHT (range: 10−12 to 10−4 M) were incubated with [3H]mibolerone and AR-LBD using the conditions described above. Following incubation, the ligand bound AR-LBD complex was isolated using BiogelHT hydroxyapatite, washed and counted in a scintillation counter after adding scintillation cocktail.
Measurement: IC50 = 92.2 nM (pChEMBL 7.039999961853027)
Descriptors: MW 357.27, ALogP 1.7, HBA 6, HBD 2, PSA 103.83, QED 0.81
Compound (SMILES): CCN1CC2(CCN(CCc3cc(F)ccc3F)CC2)O[C@H](C)C1=O
InChIKey: KALIKXMQWFLZKB-CQSZACIVSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain membranes by microbeta scintillation counting method
Measurement: Ki = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 352.43, ALogP 2.61, HBA 3, HBD 0, PSA 32.78, QED 0.84
Compound (SMILES): CN1CCc2ccc(OCCCCN3CCN(c4cccc(C(F)(F)F)c4)CC3)cc2C1=O
InChIKey: NWSWBVKRQJZUCZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 11.8 nM (pChEMBL 7.929999828338623)
Descriptors: MW 461.53, ALogP 4.31, HBA 4, HBD 0, PSA 36.02, QED 0.58
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc(F)cc2)cc1
InChIKey: RNTJUUSYPCOMRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 416.46, ALogP 1.04, HBA 5, HBD 4, PSA 147.46, QED 0.53
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3ccc(C(F)(F)F)cc23)C1=O
InChIKey: QAPTWHXHEYAIKG-RCOXNQKVSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 506.57, ALogP 3.48, HBA 6, HBD 3, PSA 99.25, QED 0.57
Compound (SMILES): O=C(NCc1ccccc1)c1ccc(S(=O)(=O)NCc2ccccc2)cc1
InChIKey: QDGVJMITKNOVTP-UHFFFAOYSA-N
Target: LIM domain kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P53671
Assay: Affinity Biochemical interaction (RapidFire MS assay) EUB0000285b LIMK2
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.47, ALogP 3.1, HBA 3, HBD 2, PSA 75.27, QED 0.66
Compound (SMILES): CN(C)CC/C=C/c1cccnc1
InChIKey: ZZHZSKGOOLOJFA-ZZXKWVIFSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]nicotine from dopamine D3 receptor (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 176.26, ALogP 2.05, HBA 2, HBD 0, PSA 16.13, QED 0.7
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(S(=O)(=O)Nc3nccs3)cc2)c1C
InChIKey: RRKBFCHMSRWBJV-GIJQJNRQSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 436.55, ALogP 1.39, HBA 9, HBD 3, PSA 140.18, QED 0.3
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay
Measurement: Kd = 0.1 nM (pChEMBL 10)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): CCN(CC)C(=O)Oc1ccc(/C=C/C(=O)N2CCc3ccccc3C2)cc1OC
InChIKey: XINGJGMSNDJSNH-ACCUITESSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 13600 nM (pChEMBL 4.869999885559082)
Descriptors: MW 408.5, ALogP 4.13, HBA 4, HBD 0, PSA 59.08, QED 0.67
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(N)(=O)=O)CC3)cc2)nc2sccc12
InChIKey: WTHHTULGDNIPBZ-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase assessed as inhibition of biotin-dUTP incorporation into wild type RT measured after 1 hr by ELISA
Measurement: IC50 = 713 nM (pChEMBL 6.150000095367432)
Descriptors: MW 561.69, ALogP 4.71, HBA 9, HBD 2, PSA 137.47, QED 0.31
Compound (SMILES): Cc1cc(-c2cnc3[nH]cc(-c4ccncc4)c3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: ZMCCTUGKELKLJP-INIZCTEOSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using S-mephenytoin as substrate measured after 5 to 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 408.51, ALogP 5.35, HBA 3, HBD 1, PSA 61.88, QED 0.49
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)c(Cl)c2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: UTKUVLWIEWNEAC-RYUDHWBXSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R phosphorylation in M-CSF induced human THP1 cells incubated for 30 mins by ELISA assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 435.94, ALogP 3.62, HBA 9, HBD 3, PSA 115.41, QED 0.54
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CCC2)c2cc(-c3ccc(C(F)(F)F)s3)cnc21
InChIKey: VBYDZMQKWHOANY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.39, ALogP 2.71, HBA 6, HBD 0, PSA 60.13, QED 0.68
Compound (SMILES): CCNc1ncc2c(n1)N(C)CCN(c1cccc(O[C@@H](CCNC)c3ccccc3)c1)C2=O
InChIKey: MGGCXTKDCMPNFI-QHCPKHFHSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: NET: Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding 1 μM. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
Measurement: Ki = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 460.58, ALogP 3.73, HBA 7, HBD 2, PSA 82.62, QED 0.5
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: VEGQLNMUJOVTKQ-AECWIZBESA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 4897.79 nM (pChEMBL 5.309999942779541)
Descriptors: MW 1247.51
Compound (SMILES): C[C@@](O)(CS(C)(=O)=O)C(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: VIHNKLOUNODTJW-XWVZOOPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 677.63, ALogP 4.42, HBA 6, HBD 2, PSA 117.61, QED 0.33
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1cncc2scnc12
InChIKey: MURNDAWLFYCTAR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay
Measurement: Ki = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 421.82, ALogP 4.59, HBA 6, HBD 2, PSA 92.79, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: AJVDIBTZNDJXEE-JMHPHXCKSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human MMP9 using 3163v as substrate preincubated for 15 mins followed by substrate addition and measured after 40 mins by fluorometric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1080.23
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(S(N)(=O)=O)cc2)c1C
InChIKey: FQHFSRHRIAXUPP-WYMPLXKRSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 488, ALogP 3.84, HBA 9, HBD 2, PSA 128.15, QED 0.31
Compound (SMILES): O=C(Nc1cccnn1)N1CC(C/C=C/c2cncc(Oc3ccc(C(F)(F)F)cn3)n2)C1
InChIKey: WBFGOFIEIRLCBO-DAFODLJHSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000540a HTR2A
Measurement: Ki = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 457.42, ALogP 4.04, HBA 7, HBD 1, PSA 106.02, QED 0.6
Compound (SMILES): O=C(O)c1cccc2c1NC(c1ccc(F)cc1)C1CC(Sc3ccccc3[N+](=O)[O-])C(Cl)C21
InChIKey: PFNDLHUUVRPUCP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P35236
Assay: Inhibition of HEPTP (unknown origin)
Measurement: IC50 = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 498.96, ALogP 6.47, HBA 5, HBD 2, PSA 92.47, QED 0.24
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3ccc(N)nc3)cc1N(c1ccc(Cl)cc1)C[C@H]2C
InChIKey: SBRJLPKKZHHGCO-CQSZACIVSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD2 (unknown origin) using biotinylated JQ1 analog as substrate measured after 20 mins by AlphaLISA assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 416.92, ALogP 5.13, HBA 6, HBD 1, PSA 72.86, QED 0.49
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(F)cc3F)s2)cc1
InChIKey: ZYPBPRUPMVUKSS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 450.47, ALogP 5.58, HBA 5, HBD 1, PSA 68.29, QED 0.39
Compound (SMILES): Cn1cncc1-c1ccc2cnc(NC(=O)c3ccnc(N4CC(N)C4)c3)cc2c1
InChIKey: NQRNCMCZKKSTEC-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].
Measurement: EC50 = 2498 nM (pChEMBL 5.599999904632568)
Descriptors: MW 399.46, ALogP 2.43, HBA 7, HBD 2, PSA 101.96, QED 0.55
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(c2cc(-c3ccccc3O)nnc2N)CC1
InChIKey: AQTNUGRRZDRZIA-UHFFFAOYSA-N
Target: Protein polybromo-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U86
Assay: Binding affinity to polybromo-1 (2) (unknown origin) by ITC analysis
Measurement: Kd = 3655 nM (pChEMBL 5.440000057220459)
Descriptors: MW 371.44, ALogP 2.49, HBA 7, HBD 2, PSA 104.81, QED 0.84
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(C)c3ccccc34)cc2)cc1
InChIKey: QRCCYPSGLCYDNW-NDEPHWFRSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in inositol phosphate accumulation in presence of terbium cryptate-labeled anti IP1/d2-labelled IP1 measured after 120 mins by HTRF assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 508.66, ALogP 5.83, HBA 4, HBD 1, PSA 53.01, QED 0.39
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cc1c(Nc2ccc(S(=O)(=O)N3CCN(C)CC3)cc2F)nc2ccc(-c3cnn(C4CC4)c3)cn2c1=O
InChIKey: JYTISQGEFSHUIR-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Selectivity interaction (BROMOscan™ panel (DiscoverX)) EUB0000253b CECR2
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 537.62, ALogP 3.02, HBA 9, HBD 1, PSA 104.84, QED 0.4
Compound (SMILES): FCCCN1CC(Nc2ccc([C@@H]3c4ccc5[nH]ncc5c4C[C@@H](C(F)F)N3CC(F)F)nc2)C1
InChIKey: FWWHNGKEZAFESY-GMAHTHKFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 494.51, ALogP 4.26, HBA 5, HBD 2, PSA 60.08, QED 0.44
Compound (SMILES): Cc1nc(OCc2ccc(F)cc2)c(C(=O)NC2CCCCCC2)cc1Br
InChIKey: LEHIEWISZPIBHW-UHFFFAOYSA-N
Target: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 435.34, ALogP 5.32, HBA 3, HBD 1, PSA 51.22, QED 0.65
Compound (SMILES): Nc1nn2c(-c3ccc(Br)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: VPJWECUQRFSGFO-WCWDXBQESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 472.33, ALogP 3.8, HBA 8, HBD 2, PSA 141.09, QED 0.43
Compound (SMILES): O=C1c2nc3ccccc3n2CCN1CCCCOc1ccc(OC(F)(F)F)cc1
InChIKey: QRCUMXUPIXTGPF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.4, ALogP 4.25, HBA 5, HBD 0, PSA 56.59, QED 0.54
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4cnc5ccccc5c4)cc3c2)cn1
InChIKey: GUGOTVDQIVQZBF-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 379.42, ALogP 4.44, HBA 5, HBD 1, PSA 72.7, QED 0.5
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-DOQBYECHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): C=CC(=O)Nc1ccc(-c2ccnc(Nc3cnn(CCOC)c3)n2)cc1
InChIKey: CKHJIDHRSXTJER-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 364.41, ALogP 2.85, HBA 7, HBD 2, PSA 93.96, QED 0.6
Compound (SMILES): CC[C@H](N[C@@H]1CC[C@@]2(OC)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3C)[C@H]1O5)C(=O)O
InChIKey: FGPMICJYDSZBIT-AXENNSGJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 572 nM (pChEMBL 6.239999771118164)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.69
Compound (SMILES): C=CCOc1ccc2oc(CC)cc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: UXEFZEYHZIIDPC-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C INI receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 271.36, ALogP 3.62, HBA 3, HBD 1, PSA 48.39, QED 0.82
Compound (SMILES): COc1cc(OC)c2c(N3CCN(C)CC3)nc(-c3cc(C)c(OCCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: NTUCJWZWDDQYER-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC4 (627 to end residues) expressed in baculovirus infected Sf9 insect cells using AcLeu-Gly-Lys(Tfa)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 537.66, ALogP 4.13, HBA 9, HBD 2, PSA 109.28, QED 0.21
Compound (SMILES): C=CC(=O)N1CCC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: DNWIBFXHQBOSSU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using ULight - 4E - BP1( Thr37 / Thr46 ) as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 686 nM (pChEMBL 6.159999847412109)
Descriptors: MW 391.48, ALogP 3.23, HBA 4, HBD 2, PSA 90.98, QED 0.74
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(C(=O)O)cc1
InChIKey: GTVGUYLLAFHOLS-SRZZPIQSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 154.4 nM (pChEMBL 6.809999942779541)
Descriptors: MW 388.39, ALogP 2.93, HBA 8, HBD 2, PSA 118.42, QED 0.31