lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOc1ccc2c(c1[C@@H]1C[C@H]1CN)CCO2.Cl
InChIKey: CZVVNGCGYYHXBE-QLSWKGBWSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A 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 = 977.24 nM (pChEMBL 6.010000228881836)
Descriptors: MW 233.31, ALogP 2.08, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CC#CC(=O)Nc1cc2cc(-c3cnn(C)c3)ccc2cn1
InChIKey: VDHIIIYZVNENLN-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The screening assay for DYRK1A kinase activity : Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A 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 DYRK1A 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).The Emission ratio (Em) was calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation was then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves were generated and inhibitory concentration (IC50) values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 290.33, ALogP 2.6, HBA 4, HBD 1, PSA 59.81, QED 0.74
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Nc1n[nH]c(N2CCC(N3C[C@H](CO)OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: NFCCGJZRWCEETB-DLBZAZTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of tracer red binding to human ERG expressed in HEK293 cell membranes measured after 2 to 6 hrs by fluorescence polarization assay
Measurement: IC50 = 72000 nM (pChEMBL 4.139999866485596)
Descriptors: MW 406.92, ALogP 1.31, HBA 7, HBD 3, PSA 103.53, QED 0.69
Compound (SMILES): COc1cc(Nc2nc(N)nc3c2ncn3Cc2ccc(C(=O)Nc3ccccc3N)cc2)cc(OC)c1
InChIKey: BZGXWZHACIVINX-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate by Fluorescence analysis
Measurement: IC50 = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 510.56, ALogP 4.05, HBA 10, HBD 4, PSA 155.23, QED 0.23
Compound (SMILES): CCOC(=O)CNc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: ZMVUYNQVYVTCAD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 404.43, ALogP 2.1, HBA 9, HBD 2, PSA 116.54, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCNc2ccccc2)CC1
InChIKey: BZPOPHHMWUCUHD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 407.89, ALogP 4.13, HBA 3, HBD 2, PSA 44.37, QED 0.68
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccc(F)cc2)cc1
InChIKey: NLPAQCHZGISERZ-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 489.54, ALogP 4.69, HBA 7, HBD 3, PSA 118.96, QED 0.37
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in IL-23 stimulated human Kit225 T cells by luciferase reporter gene assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: MAEMKRFOORLALZ-YEJMJCSASA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 1394.69
Compound (SMILES): Cl.O=C([C@@H](Cc1cccc(C(F)(F)F)c1)NS(=O)(=O)c1cc(F)c2c(c1)CCNC2)N1CCCC1
InChIKey: ZADKZNVAJGEFLC-ZMBIFBSDSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Selectivity interaction (Methyltransferase panel) EUB0000196bCl DNMT1
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.53, ALogP 3, HBA 4, HBD 2, PSA 78.51, QED 0.6
Compound (SMILES): Nc1nc2sc(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)o3)cc2c(=O)[nH]1
InChIKey: LYDGQYDYRQVOBF-ZDUSSCGKSA-N
Target: Bifunctional purine biosynthesis protein ATIC (SINGLE PROTEIN), Homo sapiens
UniProt: P31939
Assay: Inhibition of human full length N-terminal His-tagged ATIC expressed in Chinese Hamster MTXRII-OuaR2-4 R2 cells assessed as reduction in THF formation using 10-CHOTHF as substrate by spectrophotometric method
Measurement: Ki = 24710 nM (pChEMBL 4.610000133514404)
Descriptors: MW 462.48, ALogP 1.77, HBA 8, HBD 5, PSA 188.61, QED 0.26
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1F
InChIKey: NEGIWTYBODMDQN-MHZLTWQESA-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 509.62, ALogP 6.55, HBA 3, HBD 1, PSA 49.77, QED 0.35
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccccc4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: JDOWDLRLLSFBOY-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 514.61, ALogP 6.74, HBA 6, HBD 1, PSA 76.88, QED 0.28
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(-c3ccc4ccccc4c3)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: SLPDXDVCXNVEEV-YJLRWSCOSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 8.872 nM (pChEMBL 8.050000190734863)
Descriptors: MW 1150.36
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-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 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CC(C)O)C(=O)NCc1ccc(Cl)cc1)c1sccc1C
InChIKey: WLGKWBVRCUZNJF-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 = 28840.32 nM (pChEMBL 4.539999961853027)
Descriptors: MW 517.16, ALogP 6.29, HBA 5, HBD 2, PSA 52.57, QED 0.31
Compound (SMILES): Cc1c(-c2cnc3[nH]ncc3c2)ccc2c3oc(CN)nc3c(=O)n(C3CC3)c12
InChIKey: WNQBSZMKYWMZEY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 45080 nM (pChEMBL 4.349999904632568)
Descriptors: MW 386.42, ALogP 3.18, HBA 7, HBD 2, PSA 115.62, QED 0.49
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: SLPNWORIUMAUFP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Receptor Binding Assay: 5-HT2A:(1) The prepared membrane was applied with 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 Methysergide (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-Ketanserin 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 of the reaction tubes was incubated at 37° C. for 15 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.(6) The scintillation vial were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 409.53, ALogP 2.91, HBA 5, HBD 0, PSA 45.25, QED 0.66
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](Cc3c[nH]c4ccccc34)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: FPAJEPLZUWCXEI-PGNOFCDOSA-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 = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 503.6, ALogP 2.97, HBA 6, HBD 4, PSA 107.05, QED 0.41
Compound (SMILES): Cc1nc2nc(-c3cccnc3)nn2c(C)c1CC(=O)Nc1cccc(C(F)(F)F)c1
InChIKey: MTJCWZPTCSKXKK-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human TRKA at inactive state by kinetic based analysis
Measurement: Ki = 65.84 nM (pChEMBL 7.179999828338623)
Descriptors: MW 426.4, ALogP 4, HBA 6, HBD 1, PSA 85.07, QED 0.53
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-AKSMUQGVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 489.78 nM (pChEMBL 6.309999942779541)
Descriptors: MW 1117.33
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3c(F)cccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: UHXVSCQTWQLUSR-GLEMDPEOSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 1092.25
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(Cl)cc2)c1C
InChIKey: QZKHIYMJTANUNW-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 443.36, ALogP 5.84, HBA 7, HBD 1, PSA 67.99, QED 0.31
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(C)c3ccc(C(F)(F)F)cc34)cc2)cc1
InChIKey: KOQJZRRRDHXPJJ-MHZLTWQESA-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 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 576.66, ALogP 6.85, HBA 4, HBD 1, PSA 53.01, QED 0.3
Compound (SMILES): Cc1ccc(CNC(=O)C(CC(C)O)N(C)CCC=C(c2sccc2C)c2sccc2C)cc1
InChIKey: DDPFFCOBMMTWNP-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 496.74, ALogP 5.94, HBA 5, HBD 2, PSA 52.57, QED 0.35
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2ccc3c(N4CCOCC4)c(C(C)=O)c(=O)oc3c2)ncc1F
InChIKey: RDOKVGWGKMHBMG-UHFFFAOYSA-N
Target: CDK3/Cyclin E (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK3/Cyclin E (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay
Measurement: IC50 = 1506 nM (pChEMBL 5.820000171661377)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3
Compound (SMILES): C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BQMSKLCEWBSPPY-IKVTXIKFSA-N
Target: G-protein coupled receptor 183 (SINGLE PROTEIN), Homo sapiens
UniProt: P32249
Assay: Agonist activity at Go2-q-coupled EBI2 (unknown origin) expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis
Measurement: EC50 = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 418.66, ALogP 5.47, HBA 3, HBD 3, PSA 60.69, QED 0.52
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: YJQSLXCSWOBYML-MCRGWJRVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 48.98 nM (pChEMBL 7.309999942779541)
Descriptors: MW 1097.29
Compound (SMILES): CN1C(=O)c2ccccc2N(C)c2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: XDCQYSVFUPULSL-HDJSIYSDSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of recombinant human ERK5 using myelin basic protein as substrate by [gamm33P]ATP based HotSpot radiometric assay
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 352.44, ALogP 3.15, HBA 5, HBD 2, PSA 68.7, QED 0.87
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CO)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: IZZFNAUKHJUKPH-MTOWIIDVSA-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 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 404.46, ALogP 0.23, HBA 7, HBD 4, PSA 111.49, QED 0.55
Compound (SMILES): Cc1c(-c2nn(-c3ccccc3)cc2/C=N/O)nnn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: RHZYCASJFPXTCW-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 423.46, ALogP 1.88, HBA 9, HBD 2, PSA 141.28, QED 0.29
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-ZIAGYGMSSA-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 = 486 nM (pChEMBL 6.309999942779541)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-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 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): O=c1[nH]nc(-c2ccc(Cl)c(C(F)(F)F)c2)o1
InChIKey: SBBOPUCCCOEMDA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 264.59, ALogP 2.7, HBA 3, HBD 1, PSA 58.89, QED 0.86
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)ccc2n1
InChIKey: AGMGRCAUAZCHPG-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: O00238
Assay: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 29.4 nM (pChEMBL 7.53000020980835)
Descriptors: MW 437.52, ALogP 5.07, HBA 5, HBD 1, PSA 45.46, QED 0.43
Compound (SMILES): C[C@@H]1CN(c2ccc(S(C)(=O)=O)cc2)CCN1c1nccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: FEGJQPCXQMHGGC-JPAYEOGSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in pooled human liver microsomes using midazolam as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.68, ALogP 2.26, HBA 8, HBD 2, PSA 115.73, QED 0.61
Compound (SMILES): C[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-GUYCJALGSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human AMCase expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): Cc1nnc(-c2ccc3cnc(NC(=O)c4ccnc(N(C)C5CCN(C)CC5)c4)cc3c2)s1
InChIKey: ARQUTMKPMAEVSS-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 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 473.61, ALogP 4.24, HBA 8, HBD 1, PSA 87.14, QED 0.46
Compound (SMILES): COC(=O)NS(=O)(=O)c1sc(CC(C)C)cc1-c1cccc(C(=O)Cn2ccnc2C(C)(C)C)c1
InChIKey: SPDXVIKELDWSMA-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Displacement of [125I]Sar-Ile-angiotensin 2 from human AT1 receptor expressed in HEK293 cells incubated for 240 mins by radiometric scintillation analysis
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 517.67, ALogP 5.04, HBA 8, HBD 1, PSA 107.36, QED 0.42
Compound (SMILES): Nc1nccc(COc2ccc3nc(NC4CCCCC4)sc3c2)c1Cl
InChIKey: ZXYVWKYLUPYZGL-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Binding affinity to human wild type PDGFRalpha (V575 to D1002 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 388.92, ALogP 5.25, HBA 6, HBD 2, PSA 73.06, QED 0.62
Compound (SMILES): COc1ccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3c2)cc1
InChIKey: OQKZYTUPMGUCDP-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 sf9 insect cells using Boc-Lys(TFA)-AM as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 410.47, ALogP 4.02, HBA 5, HBD 4, PSA 116.34, QED 0.23
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)O)C(C)C)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: QLMICPWFXLJOEI-AANUSGNESA-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 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 579.69, ALogP 2.33, HBA 8, HBD 5, PSA 140.59, QED 0.3
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity : For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 25 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititer plate (from Greiner, TC plate, black with clear base) and incubated at 37° C./5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 1× SmartBlock (from CANDOR Bioscience GmbH), 4.5 mM Probenecid, 5 μM Fluo-8 AM, 0.016% Pluronic, 0.04% Brilliant black] and incubated at 37° C./5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode/2 mM CaCl2. 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C./5% CO2 for 10 minutes. The FP receptor is activated by adding 20 μl of 3 nM (final concentration) PGF2α in calcium-free Tyrode/2 mM CaCl2/0.04% Brilliant black, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra, Molecular Devices) for 120 seconds.
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): CC1(CN)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: HFZSVNQUAOVFHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Reversible inhibition of wild-type human SHP2 using DiFMUP as substrate and measured by jump dilution assay
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
Compound (SMILES): CON(C)C(=O)Oc1ccc(-c2cc(=O)c3c(O)cc(OC(=O)N(C)OC)cc3o2)cc1
InChIKey: MAYVYUJUNJKXFY-UHFFFAOYSA-N
Target: Butyrylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JKC1
Assay: Inhibition of rat serum Butyrylcholine esterase using butyrylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 19700 nM (pChEMBL 4.710000038146973)
Descriptors: MW 444.4, ALogP 3.15, HBA 9, HBD 1, PSA 127.98, QED 0.59
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(C(=O)NCCNC(=O)CCc4cn(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)cn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OTWPYWJMLIDHOJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Binding affinity to human muscarinic M2 receptor expressed in CHO-K9 cells assessed as unspecific binding at Kd incubated in dark at 22 degree C for 2 hrs in presence of atropine by FACSCantoII flow cytometric saturation binding study relative to control
Measurement: Kd = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 984.17, ALogP 6.15, HBA 11, HBD 3, PSA 188.19, QED 0.05
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)F
InChIKey: HHXTYKXNOKWJQP-FATZIPQQSA-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 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 494.51, ALogP 4.45, HBA 5, HBD 2, PSA 60.08, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: ZSYKTLDQSMAEFY-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 74.4 nM (pChEMBL 7.130000114440918)
Descriptors: MW 488.42, ALogP 1.59, HBA 5, HBD 4, PSA 147.46, QED 0.27
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3ccc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)cc3C2)cc1
InChIKey: WQBKMBBBWFAMFH-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 (781 to end residues) using GGEEEEYFELVKKKK as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): CCOc1ccc2c(c1[C@@H]1C[C@H]1CN)CCO2.Cl
InChIKey: CZVVNGCGYYHXBE-QLSWKGBWSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A 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 = 976 nM (pChEMBL 6.010000228881836)
Descriptors: MW 233.31, ALogP 2.08, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CC#CC(=O)Nc1cc2cc(-c3cnn(C)c3)ccc2cn1
InChIKey: VDHIIIYZVNENLN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 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 ratio of coumarin emission/fluorescein emission. 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%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 508 nM (pChEMBL 6.289999961853027)
Descriptors: MW 290.33, ALogP 2.6, HBA 4, HBD 1, PSA 59.81, QED 0.74
Compound (SMILES): c1ccc(Cc2ccc(-c3coc4ccc(-c5cn[nH]c5)nc34)cc2)cc1
InChIKey: JOZUGIHTSIWTIK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 351.41, ALogP 5.48, HBA 3, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Nc1n[nH]c(N2CCC(N3C[C@H](CO)OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: NFCCGJZRWCEETB-DLBZAZTESA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: AMCase Activity Assay: An enzymatic assay with recombinant human AMCase was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC:276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-Methylumbelliferyl B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm. Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of hAMCase recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Buffer (pH 10.5) to each well. The fluorescence of the reaction product was measured in Tecan Spark multimode plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 406.92, ALogP 1.31, HBA 7, HBD 3, PSA 103.53, QED 0.69
Compound (SMILES): CCOC(=O)CNc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: ZMVUYNQVYVTCAD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 404.43, ALogP 2.1, HBA 9, HBD 2, PSA 116.54, QED 0.47
Compound (SMILES): O=C(CCCN1C2CCC1CN(c1ccc(Cl)cn1)C2)c1ccc(F)cc1
InChIKey: UPBSKELQKAHWLX-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 120.23 nM (pChEMBL 6.920000076293945)
Descriptors: MW 387.89, ALogP 4.19, HBA 4, HBD 0, PSA 36.44, QED 0.7
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCNc2ccccc2)CC1
InChIKey: BZPOPHHMWUCUHD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in calcium mobilization measured at 2 sec intervals for 180 secs by Fluo-4AM dye based fluorescence assay
Measurement: EC50 = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 407.89, ALogP 4.13, HBA 3, HBD 2, PSA 44.37, QED 0.68
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(F)cn2)c1OC
InChIKey: BBRMAVGRWHNAIG-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9R117
Assay: Inhibition of TYK2 in mouse whole blood assessed as decrease in IFNalpha-induced STAT5 phosphorylation
Measurement: IC50 = 481 nM (pChEMBL 6.320000171661377)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: MAEMKRFOORLALZ-YEJMJCSASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR stably expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 1 hr by liquid scintillation counting assay
Measurement: EC50 = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 1394.69
Compound (SMILES): Cl.O=C([C@@H](Cc1cccc(C(F)(F)F)c1)NS(=O)(=O)c1cc(F)c2c(c1)CCNC2)N1CCCC1
InChIKey: ZADKZNVAJGEFLC-ZMBIFBSDSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Selectivity interaction (Methyltransferase panel) EUB0000196bCl DOT1L
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.53, ALogP 3, HBA 4, HBD 2, PSA 78.51, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccccc4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: JDOWDLRLLSFBOY-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 9.05 nM (pChEMBL 8.039999961853027)
Descriptors: MW 514.61, ALogP 6.74, HBA 6, HBD 1, PSA 76.88, QED 0.28
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(-c3ccc4ccccc4c3)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: SLPDXDVCXNVEEV-YJLRWSCOSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC4R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 1150.36
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CC(C)O)C(=O)NCc1ccc(Cl)cc1)c1sccc1C
InChIKey: WLGKWBVRCUZNJF-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 = 13182.57 nM (pChEMBL 4.880000114440918)
Descriptors: MW 517.16, ALogP 6.29, HBA 5, HBD 2, PSA 52.57, QED 0.31
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: SLPNWORIUMAUFP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Receptor Binding Assay: 5-HT7: (1) The prepared membrane was applied with 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 (��)-pindolol (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-5-CT 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 of the reaction tubes was incubated at 25° C. for 120 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 = 28.1 nM (pChEMBL 7.550000190734863)
Descriptors: MW 409.53, ALogP 2.91, HBA 5, HBD 0, PSA 45.25, QED 0.66
Compound (SMILES): Cc1nc2nc(-c3cccnc3)nn2c(C)c1CC(=O)Nc1cccc(C(F)(F)F)c1
InChIKey: MTJCWZPTCSKXKK-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human TRKA at active state by kinetic based analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 426.4, ALogP 4, HBA 6, HBD 1, PSA 85.07, QED 0.53
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-AKSMUQGVSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 1117.33
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3c(F)cccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: UHXVSCQTWQLUSR-GLEMDPEOSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC4R expressed in HEK293 cell membranes incubated for 120 mins
Measurement: Ki = 0.02138 nM (pChEMBL 10.670000076293945)
Descriptors: MW 1092.25
Compound (SMILES): Cc1ccc(CNC(=O)C(CC(C)O)N(C)CCC=C(c2sccc2C)c2sccc2C)cc1
InChIKey: DDPFFCOBMMTWNP-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 = 5495.41 nM (pChEMBL 5.260000228881836)
Descriptors: MW 496.74, ALogP 5.94, HBA 5, HBD 2, PSA 52.57, QED 0.35
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2ccc3c(N4CCOCC4)c(C(C)=O)c(=O)oc3c2)ncc1F
InChIKey: RDOKVGWGKMHBMG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/Cyclin D1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay
Measurement: IC50 = 471 nM (pChEMBL 6.329999923706055)
Descriptors: MW 508.48, ALogP 4.32, HBA 9, HBD 1, PSA 106.79, QED 0.3