lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C(=O)c1ccc(N(CCN2CCCC2)S(=O)(=O)c2ccc(F)cc2)cc1)[C@@H](Cc1ccccc1)C(=O)O
InChIKey: SESRJRLBHQWLSW-MHZLTWQESA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Inhibition of recombinant human IRAP expressed in HEK293 cells using L-AMC as substrate preincubated for 30 mins followed by substrate addition measured every 3 mins for 1 hr by flourescence assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 553.66, ALogP 3.88, HBA 5, HBD 1, PSA 98.23, QED 0.39
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H]2CC23CCN(CCCCCn2c(=O)ccc4cc(ccc42)-c2cnc1o2)CC3
InChIKey: ONEHGRSVCWEICS-IZLXSDGUSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 572.75, ALogP 6.03, HBA 7, HBD 1, PSA 97.44, QED 0.35
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccc(Cl)cc1
InChIKey: HLUKJXBXVAJVDL-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-P129 from human histamine H3 receptor expressed in sf9 insect cell membranes co-expressing Galphai2/Gbeta1gamma2 incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 17782.79 nM (pChEMBL 4.75)
Descriptors: MW 394.93, ALogP 2.99, HBA 4, HBD 4, PSA 118.42, QED 0.34
Compound (SMILES): CCCCc1cc2c(O)cc(C3(CCCC)CCCCC3)cc2oc1=O
InChIKey: ZSDRKMOWPYPBBK-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 356.51, ALogP 6.23, HBA 3, HBD 1, PSA 50.44, QED 0.6
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6cccc(C)c6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: WKMFLLKOZSRSEI-OWDVXBOWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 56.2 nM (pChEMBL 7.25)
Descriptors: MW 576.78, ALogP 7.01, HBA 5, HBD 1, PSA 42.96, QED 0.31
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4ccc(Cl)cc43)C[C@@H]21
InChIKey: ZDKFHGLDLBLVNB-MRSOFBGISA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO by QPatch assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 428.36, ALogP 5.75, HBA 3, HBD 1, PSA 46.92, QED 0.56
Compound (SMILES): O=C(CCCCCCCCCCCCCCC(=O)NCCCCCCCCCCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43)NCCCCCCCCCCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43
InChIKey: SNCRHEFSSRKCHT-VQVSISRWSA-N
Target: Glycine receptor (alpha-1/beta) (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1315.84
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2cc(Br)cc(C(=O)OC)c2)c1=O
InChIKey: KIHKGIDJKYCFHB-GOSISDBHSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human recombinant DPP4 using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by fluorescence based microplate reader assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 489.37, ALogP 1.56, HBA 8, HBD 1, PSA 99.56, QED 0.51
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N1CC[C@H](c2ccccc2)[C@@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: RMTFEXADGYFGKN-IHGMTAJESA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll and rGFP-CAAX assessed as induction of recruitment of Galpha12 to cell membrane using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 1591.89
Compound (SMILES): COc1cc2nc(-c3ccc(C)o3)cc(NCc3ccc(C(=O)NO)cc3)c2cc1OC
InChIKey: SIEVVDPSPBNVMH-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of full length human C-terminal His-tagged HDAC3/human N-terminal GST-agged NCOR2 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 433.46, ALogP 4.55, HBA 7, HBD 3, PSA 105.85, QED 0.29
Compound (SMILES): CC1(C)CC[C@]2(C(=O)OCc3ccccc3)CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)Cc6nccnc6[C@@](C)(COC(=O)CCC(=O)OCCOCCOCCOCCO)[C@@H]5CC[C@]43C)[C@@H]2C1
InChIKey: UIKUUBFXGRJBJN-GLYFMXDRSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-glycoprotein mediated multidrug resistance in human KBV cells assessed as reversal of resistance to vincristine-induced cytotoxicity by measuring vincristine IC50 at 5 uM measured after 72 hrs by MTT assay
Measurement: IC50 = 4.02 nM (pChEMBL 8.399999618530273)
Descriptors: MW 873.14, ALogP 7.92, HBA 12, HBD 1, PSA 152.6, QED 0.06
Compound (SMILES): Cc1ccc(S(=O)(=O)SCc2ccc(Cl)cc2)cc1
InChIKey: CBQWJVRTMNAWFV-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured by Ellman's method
Measurement: IC50 = 314.5 nM (pChEMBL 6.5)
Descriptors: MW 312.84, ALogP 4.27, HBA 3, HBD 0, PSA 34.14, QED 0.79
Compound (SMILES): O=C(O)c1cn(Cc2ccc(Cl)c(F)c2)cc(O)c1=O
InChIKey: UGSKTSHAXSPBHX-UHFFFAOYSA-N
Target: Tripartite terminase subunit 3 (SINGLE PROTEIN), Human betaherpesvirus 5
UniProt: P16732
Assay: Inhibition of human cytomegalovirus pUL89 endonuclease activity using 60 bp dsDNA substrate incubated for 30 mins by ELISA-based biochemical assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 297.67, ALogP 2.09, HBA 4, HBD 2, PSA 79.53, QED 0.91
Compound (SMILES): Cc1nc2c3cc(-c4ccncc4C)c(Cl)cc3[nH]c(=O)n2n1
InChIKey: FVTXWRGKBOWNPA-UHFFFAOYSA-N
Target: Hepatitis A virus cellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDQ0
Assay: Displacement of FITC-labelled 5-(((8-Chloro-9-(3-methylpyridin-4-yl)-5-oxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)methyl)carbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid probe from human TIM-3 IgV domain (residues 22 to 130) expressed in Escherichia coli BL21 (DE3) by FPA competition assay
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 325.76, ALogP 2.9, HBA 5, HBD 1, PSA 75.94, QED 0.58
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: AIQRGPUFSZXKMB-WRCAVZGJSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 854.79, ALogP 4.2, HBA 6, HBD 6, PSA 185.51, QED 0.06
Compound (SMILES): CC(C)(C)c1noc(C(=O)NCc2ccc(-c3ccnc4[nH]c(C5CC5)nc34)cc2F)n1
InChIKey: QWQCLCVJZVSJFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 434.48, ALogP 4.25, HBA 6, HBD 2, PSA 109.59, QED 0.49
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(-c4cc[nH]n4)ccc32)cc1
InChIKey: PNISZNNEPJHZEF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Boc-Lys(TFA)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 792 nM (pChEMBL 6.099999904632568)
Descriptors: MW 348.41, ALogP 3.15, HBA 4, HBD 3, PSA 81.25, QED 0.5
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC(C)c1ccc(OC(F)(F)F)cc1
InChIKey: JHCLKMYQQVHYLG-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-P129 from human histamine H3 receptor expressed in sf9 insect cell membranes co-expressing Galphai2/Gbeta1gamma2 incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 14454.4 nM (pChEMBL 4.840000152587891)
Descriptors: MW 444.48, ALogP 3.24, HBA 5, HBD 4, PSA 127.65, QED 0.29
Compound (SMILES): Cc1nc2c(cnn2-c2csc(C(=O)NC3COC3)c2)cc1Nc1cc(F)ccc1Cl
InChIKey: YUDWKEAEZWLVGN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38 alpha (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis
Measurement: IC50 = 2890 nM (pChEMBL 5.539999961853027)
Descriptors: MW 457.92, ALogP 4.46, HBA 7, HBD 2, PSA 81.07, QED 0.46
Compound (SMILES): CCCCc1[nH]c(=O)c(S(=O)(=O)c2ccc(-c3ccncc3C)cc2)c(O)c1-c1c(OC)cccc1OC
InChIKey: QPOOGLDKJWMVCE-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q9WV08
Assay: Agonist activity at mouse APJ receptor assessed as effect on cAMP accumulation by cAMP-Glo assay
Measurement: EC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 534.63, ALogP 5.31, HBA 7, HBD 2, PSA 118.58, QED 0.3
Compound (SMILES): NS(=O)(=O)c1cncc(-c2ccc3ncc4nnc(C5CCOCC5)n4c3c2)c1
InChIKey: HYSFHTXNKQSESE-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length N-terminal FLAG-tagged human ATM expressed in HEK293-6E cells using biotin-PEG2-SVEPPLSQETFSD as substrate preincubated for 15 mins followed by substrate addition and measured after 90 mins in presence of ATP by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 410.46, ALogP 1.88, HBA 8, HBD 1, PSA 125.36, QED 0.55
Compound (SMILES): CNc1cc(Oc2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2)ncn1
InChIKey: YUOIOAHDJBTFGF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of GST-6His tagged VEGFR2 (unknown origin) using biotin-aminohexyl-EEEEYFELVAKKKK-NH2 peptide substrate incubated for 90 mins by HTRF assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 403.36, ALogP 4.97, HBA 5, HBD 3, PSA 88.17, QED 0.56
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: ORJHCCXQMOTJLU-IHZBLBIESA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 754.9, ALogP 0.08, HBA 7, HBD 12, PSA 299.08, QED 0.03
Compound (SMILES): Nc1cc(C2CCNC3CCC(CC3)COc3cccc(c3)Cn3cc2cn3)c2nn[nH]c2n1
InChIKey: CPXJLLGWDVECQS-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Chlorination Assay (APF Assay): MPO chlorination activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Aminophenyl fluorescein (APF, Invitrogen Cat. #A36003). APF is cleaved by (OCl) to yield the fluorescent compound fluorescein. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 120 mM NaCl to 100 nL inhibitor in 100% DMSO in a 384 well, non-binding surface clear bottom plate (Corning #3655). Enzyme, inhibitor, and chloride were preincubated for ten minutes at room temperature.After the ten minute preincubation, 25 μL of an APF mixture containing 10 mM APF, 120 mM NaCl and 10 μM H2O2 was added to the plate using the internal dispensing system of a Hammatsu FDSS 6000. Kinetic determinations were carried out immediately on the FDSS 6000 (3 minute kinetic read, 1 read every second, ex: 485 nm, em: 535 nm). IC50 values for inhibitors were calculated by taking the slope of the linear portion of the kinetic measurement (20 seconds to 80-120 secs).
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 458.57, ALogP 3.24, HBA 8, HBD 3, PSA 119.56, QED 0.4
Compound (SMILES): Cc1ccc(-c2cc3occ(CN4CCC[C@H](N)C4)c3cc2-c2ccc(C#N)cc2)cc1
InChIKey: MQEXBLBDOHQHHG-DEOSSOPVSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of N-terminal FLAG-tagged human recombinant MAO-B expressed in baculovirus-infected Sf9 cells by flow cytometry
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 421.54, ALogP 5.87, HBA 4, HBD 1, PSA 66.19, QED 0.45
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCCn1cc(cn1)-c1ncnc3ccc-2cc13
InChIKey: VWNVCKQEAMDLCY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 527.57, ALogP 3.11, HBA 9, HBD 2, PSA 140.99, QED 0.34
Compound (SMILES): C[C@H]1CN(C(=O)CCC2(c3ccccn3)NC(=O)NC2=O)CCN1c1cc(Cl)cc(Cl)c1
InChIKey: SYFMYEKYZWQZLV-XLEXHMCLSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: In Vitro Assay: ADAMTS-5:Protocol 2: The basis for the assay is the cleavage of the substrate TBIS-1 (5 FAM-TEGEARGSVILLK (5TAMRA)K-NH2) (SEQ ID No 2) by human ADAMTS-5.For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (50 mM Hepes pH7.5, 100 mM NaCl, 5 mM CaCl2, 0.1% CHAPS 1) containing hADAMTS-5 (1 ng/μL, affinity purified, followed by overnight digestion of 6His tag by thrombin and dialysis) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate TBIS-1 (10 μL, 4.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 45 min at 37° C. (Excitation 485 nm, emission 530).
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 476.36, ALogP 2.94, HBA 5, HBD 2, PSA 94.64, QED 0.65
Compound (SMILES): N#CCn1ncc(Nc2ccc(CN)cc2)c(Cl)c1=O
InChIKey: GXHSEYWYHGZDGJ-UHFFFAOYSA-N
Target: Nucleosome-remodeling factor subunit BPTF (SINGLE PROTEIN), Homo sapiens
UniProt: Q12830
Assay: Binding affinity to BPTF (unknown origin) by by BROMOscan method
Measurement: Kd = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 289.73, ALogP 1.62, HBA 6, HBD 2, PSA 96.73, QED 0.89
Compound (SMILES): O=C(NC(Cn1ccnc1)C(=O)c1cccc(F)c1)c1ccc(-c2ccc(Cl)cc2)s1
InChIKey: WVRDOEKNDRFGQZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver Microsome using S-mephenytoin as substrate preincubated for 10 mins followed by NADPH addition and further incubated for 10 mins as substrate by LC-MS/MS analysis
Measurement: IC50 = 1790 nM (pChEMBL 5.75)
Descriptors: MW 453.93, ALogP 5.09, HBA 5, HBD 1, PSA 63.99, QED 0.4
Compound (SMILES): O=C1CCc2ccc(OCCCCNCC3CC3c3cccc4ccccc34)cc2N1
InChIKey: DZIJHQWKYKVRCI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 660.7 nM (pChEMBL 6.179999828338623)
Descriptors: MW 414.55, ALogP 5.28, HBA 3, HBD 2, PSA 50.36, QED 0.47
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: YZRKLLYZJJPVLG-AXXKPAGNSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse MC5R expressed in HEK293 cells assessed as induction of cAMP level at 100 uM incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 737.91, ALogP 1.61, HBA 7, HBD 9, PSA 247.41, QED 0.04
Compound (SMILES): C[C@H]1CN(C(=O)CCC2(C3CC3)NC(=O)NC2=O)CCN1c1ccccc1
InChIKey: RVYQNGRWJSISOS-PVCZSOGJSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: In Vitro Assay: ADAMTS-5:Protocol 2: The basis for the assay is the cleavage of the substrate TBIS-1 (5 FAM-TEGEARGSVILLK (5TAMRA)K-NH2) (SEQ ID No 2) by human ADAMTS-5.For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (50 mM Hepes pH7.5, 100 mM NaCl, 5 mM CaCl2, 0.1% CHAPS 1) containing hADAMTS-5 (1 ng/μL, affinity purified, followed by overnight digestion of 6His tag by thrombin and dialysis) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate TBIS-1 (10 μL, 4.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 45 min at 37° C. (Excitation 485 nm, emission 530).
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 370.45, ALogP 1.49, HBA 4, HBD 2, PSA 81.75, QED 0.77
Compound (SMILES): O=C(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)C1(O)CCNCC1
InChIKey: WPYBKGAGWDLLGV-SGIRGMQISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in CD3 and CD28-stimulated human whole blood assessed as suppression of IL17 preincubated for 1 hr followed by CD3 and CD28 stimulation measured after 20 hrs by AlphaLISA method
Measurement: EC50 = 1940 nM (pChEMBL 5.710000038146973)
Descriptors: MW 640.59, ALogP 4.74, HBA 5, HBD 3, PSA 95.5, QED 0.32
Compound (SMILES): CC(C)C(Sc1nc2c(cnn2C)c(=O)n1-c1ccccc1)c1ccccc1
InChIKey: KPVOMFSRGWGDAC-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of human ALDH1A3 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 390.51, ALogP 4.61, HBA 6, HBD 0, PSA 52.71, QED 0.37
Compound (SMILES): Cc1ccc(Cn2c(O)nc3c(Cl)nc(N)nc32)c(F)c1
InChIKey: HVPWZMMRXNRODN-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal Grp94 (unknown origin) incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 = 318 nM (pChEMBL 6.5)
Descriptors: MW 307.72, ALogP 2.26, HBA 6, HBD 2, PSA 89.85, QED 0.71
Compound (SMILES): Cc1ccccc1-c1ccc(-c2nnc(N(C)Cc3ccc4nccn4c3)o2)cc1
InChIKey: HVRASXRMCOQSPI-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by LC-MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 395.47, ALogP 5, HBA 6, HBD 0, PSA 59.46, QED 0.42
Compound (SMILES): Cn1cnc2ncn(Cc3nn(C[C@H](F)c4ccc(Cl)cc4)c(=O)o3)c(=O)c21
InChIKey: RSSHXKVUURRAKX-LBPRGKRZSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q6RI86
Assay: Antagonist activity at rat TRPA1
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 404.79, ALogP 1.69, HBA 9, HBD 0, PSA 100.74, QED 0.5
Compound (SMILES): CCN(CCCOc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1)Cc1ccccc1OC
InChIKey: SYVZGOFSSNTPEM-QGOAFFKASA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 488.63, ALogP 5.65, HBA 6, HBD 1, PSA 62.24, QED 0.19
Compound (SMILES): NS(=O)(=O)c1ccc(N2CN(Cc3c(F)c(F)c(F)c(F)c3F)CCS2(=O)=O)cc1
InChIKey: LDGVDMSVRUABPI-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated for 15 mins by measured for 10 to 100 secs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 97.6 nM (pChEMBL 7.010000228881836)
Descriptors: MW 471.43, ALogP 1.64, HBA 5, HBD 1, PSA 100.78, QED 0.42
Compound (SMILES): O=C(NCc1ccc(CN2CCC2)cc1)c1ccc2nncn2c1
InChIKey: XCHVKCPMWXBIRJ-UHFFFAOYSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Inhibition of human His-AF9 YEATS domain and biotinylated H3K9ac peptide interaction by AlphaScreen assay
Measurement: IC50 = 984 nM (pChEMBL 6.010000228881836)
Descriptors: MW 321.38, ALogP 1.86, HBA 5, HBD 1, PSA 62.53, QED 0.78
Compound (SMILES): Cc1ccccc1-c1oc(CCC(=O)O)nc1-c1ccccc1
InChIKey: UOGWMBJTFZMJLA-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Agonist activity at human RXRbeta transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 307.35, ALogP 4.33, HBA 3, HBD 1, PSA 63.33, QED 0.76
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NCCN1CCN(CC(=O)NC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: HLVUOTLGLQRVLG-NJYVXCEBSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 846.05, ALogP -0.39, HBA 12, HBD 9, PSA 263.45, QED 0.05
Compound (SMILES): O=C1CCCc2c1cnn2-c1ccc(S(=O)(=O)Nc2ccccc2)cc1
InChIKey: GPNNPIRKRNAEGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 59600 nM (pChEMBL 4.21999979019165)
Descriptors: MW 367.43, ALogP 3.19, HBA 5, HBD 1, PSA 81.06, QED 0.77
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(NC4CCCC(O)C4)n3)cc12
InChIKey: LPMINUZUMUXWKI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 323.4, ALogP 3.04, HBA 5, HBD 3, PSA 86.72, QED 0.69
Compound (SMILES): COc1cc2c(cc1O)CN(Cc1ccccc1CNC(=O)c1ccccc1Cl)CC2
InChIKey: AIYKVNCJQXICKY-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-methylspiperone from dopamine D4 receptor (unknown origin)
Measurement: Ki = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 436.94, ALogP 4.54, HBA 4, HBD 2, PSA 61.8, QED 0.6
Compound (SMILES): CCN(Cc1ccc(-c2cn[nH]c2)cc1)C(=O)[C@@H]1CCCN(c2cccc(OC(C)(C)C(=O)N3CCNCC3)c2)C1.Cl
InChIKey: VDOZSBIDVZNELF-UFTMZEDQSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Inhibition of beta-catenin (unknown origin) transfected in HEK293 cells cotransfected with pCMV-RL assessed as reduction in luciferase activity measured after 24 hrs by TOPFlash luciferase reporter assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 558.73, ALogP 3.93, HBA 6, HBD 2, PSA 93.8, QED 0.41
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OCCCCCOc3cccc2c3)cc1OC
InChIKey: JOZMVUXPQMRQOL-KLBQNTFLSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 1491 nM (pChEMBL 5.829999923706055)
Descriptors: MW 743.94, ALogP 8.62, HBA 9, HBD 0, PSA 101.99, QED 0.21
Compound (SMILES): O=C(Nc1ccc(F)cc1)C1(C2CCC3C(CCCN3c3ccnc(C(F)(F)F)n3)C2)CCC1
InChIKey: AJWDSGNMJJFPDP-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells assessed as production of N-formylkynurenine using tryptophan as substrate in presence of inactivated fetal bovine serum
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 476.52, ALogP 5.83, HBA 4, HBD 1, PSA 58.12, QED 0.56
Compound (SMILES): CCOc1ccc2c(c1)O/C(=C\c1cc(C)c(OC(C)(C)C(=O)O)c(C)c1)C2=O
InChIKey: CENWAQSNUVVQEY-ODLFYWEKSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human PPARdelta transfected in human HEK293 cells incubated for 18 hrs by Renilla/Firefly dual-luciferase reporter assay
Measurement: EC50 = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 396.44, ALogP 4.56, HBA 5, HBD 1, PSA 82.06, QED 0.72
Compound (SMILES): CC(=O)NS(=O)(=O)c1ccc(N2C(=O)/C(=C\c3cn(C(C)=O)c4ccccc34)N=C2c2ccccc2)cc1
InChIKey: BTHVYQLEKGSLEW-PCLIKHOPSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human CA4 by stopped-flow assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 526.57, ALogP 3.96, HBA 7, HBD 1, PSA 117.91, QED 0.4
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OCCCCOc3cccc2c3)cc1OC
InChIKey: RDJGELWAXUTIEU-TWBLSBBDSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 584 nM (pChEMBL 6.230000019073486)
Descriptors: MW 729.91, ALogP 8.23, HBA 9, HBD 0, PSA 101.99, QED 0.21
Compound (SMILES): Cc1nc2c(C(C)c3ccc(C(F)(F)F)cc3)nn(C)c2c(=O)[nH]1
InChIKey: WQKGQDCYZQHQDM-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: PDE2 Inhibition Assay: In a typical experiment the PDE2 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. Rhesus PDE2A3 was amplified from rhesus macaque brain cDNA (Biochain Institute, Hayward, Calif.) using primers based on human PDE2A sequence (accession NM_002599.3) where the forward primer containing a Kozak consensus was 5′-gccaccatggggcaggcatgtggc-3′ and the reverse primer was 5′-tcactcagcatcaaggctgca-3′. Amplification with Easy-A High-Fidelity PCR cloning enzyme (Stratagene, La Jolla, Calif.) was 95° C. for 2 minutes followed by thirty three cycles of 95° C. for 40 seconds, 52° C. for 30 seconds, and 72° C. for 2 minutes 48 seconds. Final extension was 72° C. for 7 minutes. The PCR product was TA cloned into pcDNA3.3-TOPO (Invitrogen, Carlsbad, Calif.) according to standard protocol. A consensus sequence was developed from multiple clones and then deposited into GenBank (EU812167). AD293 cells (Stratagene, La Jolla, Calif.) with 70-80% confluency were transiently transfected with rhesus PDE2A3/pcDNA3.3-TOPO using Lipofectamine 2000 according to manufacturer specifications (Invitrogen, Carlsbad, Calif.). Cells were harvested 48 hours post-transfection and lysed by sonication (setting 3, 10×5 sec pulses) in a buffer containing 20 mM HEPES pH 7.4, 1 mM EDTA and Complete Protease Inhibitor Cocktail Tablets (Roche, Indianapolis, Ind.). Lysate was collected by centrifugation at 75,000×g for 20 minutes at 4° C. and supernatant utilized for evaluation of PDE2 activity. The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP® FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product # R8139). IMAP® technology has been applied previously to examine the effects of phosphodiesterase inhibitors (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). Assays were performed at room temperature in 384-well microtiter plates with an incubation volume of 20.2 μL. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 8 μL of each of 10 solutions differing by 3-fold in concentration, at 32 serial dilutions per plate. 100% inhibition is determined using a known PDE2 inhibitor, which can be any compound that is present at 5,000 times its Ki value in the assay described below, such as Bay 60-7550 (Ki-0.2 nM) at 1 μM concentration for 100% inhibition. Bay 60-7550 was obtained from Axxora via Fisher Scientific (cat# ALX-270-421-M025/cat#NC9314773). Put another way, any compound with Ki of 0.2 to about 2 nM could be used at 1 to 10 μM. 0% of inhibition is determined by using DMSO (1% final concentrations).
Measurement: Ki = 60.9 nM (pChEMBL 7.210000038146973)
Descriptors: MW 336.32, ALogP 3.14, HBA 4, HBD 1, PSA 63.57, QED 0.78
Compound (SMILES): NC(=O)C1CN(Cc2ccccc2Cl)c2ccccc2O1
InChIKey: VNNKVVSLTAJBOA-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 302.76, ALogP 2.59, HBA 3, HBD 1, PSA 55.56, QED 0.95
Compound (SMILES): COc1ccc(F)cc1[C@H]1C[C@@H]1CNCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: GZSCSKUGXORHGO-APWZRJJASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 4.12 nM (pChEMBL 8.380000114440918)
Descriptors: MW 396.46, ALogP 3.84, HBA 4, HBD 2, PSA 63.35, QED 0.54
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]ncc4c3N(C)C2=O)c1F
InChIKey: NAXMPDJKRUSHCA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 375.34, ALogP 2.83, HBA 5, HBD 1, PSA 83.58, QED 0.76
Compound (SMILES): C=CC(=O)N1CCCC[C@H]1c1nc(-c2ccc(C(=O)Nc3cc(-c4ccccc4)ccn3)cc2)c(C(N)=O)n1N
InChIKey: AJXRZKIHWZAXJZ-QHCPKHFHSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of full-length N-terminal GST-tagged ITK (2 to 620 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 2210 nM (pChEMBL 5.659999847412109)
Descriptors: MW 535.61, ALogP 3.92, HBA 7, HBD 3, PSA 149.23, QED 0.24
Compound (SMILES): Cn1c(Cc2nn(CCCO[Si](C)(C)C(C)(C)C)c(=O)c3ccccc23)nnc1SCCCCCCCC(=O)Nc1ccc(Cl)cc1Cl
InChIKey: UWFBQOBRCWVTNY-UHFFFAOYSA-N
Target: Interleukin-15 (SINGLE PROTEIN), Homo sapiens
UniProt: P40933
Assay: Inhibition of IL-15-induced STAT3 phosphorylation in human NK92 cells incubated for 30 mins followed by IL-15 stimulation and measured after 1 hr by alphascreen assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 731.87
Compound (SMILES): CCOC(=O)C(Nc1ccc(S(N)(=O)=O)cc1)c1ccc(OC)c(OC)c1
InChIKey: NTQILTFORVTUIH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 394.45, ALogP 2.07, HBA 7, HBD 2, PSA 116.95, QED 0.66
Compound (SMILES): Cc1ccc(-c2n[nH]cc2N2CCCNCC2)cc1
InChIKey: GEKVZXHRWKQTBA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as reduction in cAMP accumulation incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 1741 nM (pChEMBL 5.760000228881836)
Descriptors: MW 256.35, ALogP 2.18, HBA 3, HBD 2, PSA 43.95, QED 0.87
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OCC/C=C\COc3cccc2c3)cc1OC
InChIKey: CJICCQJQZUCWHW-GTKPNJOPSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 526 nM (pChEMBL 6.28000020980835)
Descriptors: MW 741.92, ALogP 8.4, HBA 9, HBD 0, PSA 101.99, QED 0.17
Compound (SMILES): CC1(N)CCN(c2ccc3c(n2)CN2CCN(c4ccc(C#N)c5ncccc45)C[C@@H]32)CC1
InChIKey: LDISRPMCMZFMTM-QHCPKHFHSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Inhibition of human TLR9 expressed in HEK293-Blue cells assessed as inhibition of R848-induced NF-kappaB/AP-1 activation measured after 20 hrs using quanti-blue as substrate by SEAP reporter gene based spectrophotometry assay
Measurement: IC50 = 56.6 nM (pChEMBL 7.25)
Descriptors: MW 439.57, ALogP 3.2, HBA 7, HBD 1, PSA 85.31, QED 0.66
Compound (SMILES): NS(=O)(=O)c1cc2cc(F)ccc2oc1=O
InChIKey: LZZPJJGCMNPSHV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 32.6 nM (pChEMBL 7.489999771118164)
Descriptors: MW 243.21, ALogP 0.58, HBA 4, HBD 1, PSA 90.37, QED 0.74
Compound (SMILES): CCCCNNC(=O)N[C@H]1CC(C(=O)O)=C[C@@H](OC(CC)CC)[C@@H]1NC(C)=O
InChIKey: KECDRMOQNBKGFQ-GVDBMIGSSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: Q2LFS1
Assay: Inhibition of Influenza A virus (A/Anhui/1/2005(H5N1) Neuraminidase H274Y mutant using MUNANA as substrate preincubated for 5 to 15 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometric method
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 398.5, ALogP 1.45, HBA 5, HBD 5, PSA 128.79, QED 0.26
Compound (SMILES): C=CC(=O)N1CCCC[C@H]1c1nc(-c2ccc(C(=O)Nc3cc(-c4ccc(F)cc4)ccn3)cc2)c(C(N)=O)n1N
InChIKey: JNXAHUQUDHQPOY-QHCPKHFHSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of full-length N-terminal GST-tagged ITK (2 to 620 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 6057 nM (pChEMBL 5.21999979019165)
Descriptors: MW 553.6, ALogP 4.06, HBA 7, HBD 3, PSA 149.23, QED 0.23
Compound (SMILES): CN(C)C(=O)N[C@H]1CC[C@H](CCNCC2CC2c2cccc3ccccc23)CC1
InChIKey: IHASGYIIIJIUCC-SUFHFGBBSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 407.4 nM (pChEMBL 6.389999866485596)
Descriptors: MW 393.58, ALogP 4.75, HBA 2, HBD 2, PSA 44.37, QED 0.67
Compound (SMILES): CCOC(=O)N1CCN(c2nc(C)cc(OCc3cn(-c4ccc(S(N)(=O)=O)cc4)nn3)n2)CC1
InChIKey: RIIITZYONLUJDQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 measured by stopped flow CO2 hydrase assay
Measurement: Ki = 33.4 nM (pChEMBL 7.480000019073486)
Descriptors: MW 502.56, ALogP 0.87, HBA 11, HBD 1, PSA 158.66, QED 0.49
Compound (SMILES): O=C(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)C1(O)CCOCC1
InChIKey: LFAYVOLNYZLVHP-SGIRGMQISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 641.58, ALogP 5.17, HBA 5, HBD 2, PSA 92.7, QED 0.35
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)NC(=O)NCCCCN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: XLJZDUXVKFPZDJ-WGXSSYHUSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK299 from human neuropeptide Y Y1 receptor in human SK-N-MC cells measured after 90 mins by scintillation counting analysis
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 1212.38
Compound (SMILES): O=C(Nc1cncc(OCC2CCN(Cc3ccccc3)CC2)c1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: MAPUWPDSUZHELW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant N-terminal His-tagged GSK3beta expressed in Escherichia coli using RRRPASVPPSPSLS RHS(pS)HQRR as substrate incubated for 30 mins in presence of ATP by Kinase-Glo reagent based luminescence assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 485.59, ALogP 4.37, HBA 6, HBD 2, PSA 96.45, QED 0.47
Compound (SMILES): CCCCCCCCC[C@]1(CO)NC[C@H](O)[C@@H](O)[C@@H]1O.Cl
InChIKey: APWLXFNCURJGTL-VZXSFKIWSA-N
Target: Alpha-galactosidase (SINGLE PROTEIN), Coffea arabica
UniProt: Q42656
Assay: Inhibition of coffee beans alpha-galactosidase using p-nitrophenyl glycoside as substrate assessed as release of p-nitrophenol measured by spectrometric assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 289.42, ALogP 0.54, HBA 5, HBD 5, PSA 92.95, QED 0.4
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N1CCC[C@H]1C(=O)N[C@H](Cc1ccc(OCc2ccccc2)c(C2CCCC2)c1)C(=O)O
InChIKey: IXTUNGODPWUWHO-PKQMNGDDSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll and rGFP-CAAX assessed as induction of recruitment of Galpha12 to cell membrane using coelenterazine luciferase substrate incubated for 5 mins by BRET assay
Measurement: EC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 1690.03
Compound (SMILES): COc1ncc(-c2cc(-c3ccnc(N4C[C@@H](C)O[C@@H](C)C4)c3)cc3c2CNC3=O)cc1NS(C)(=O)=O
InChIKey: BTLBFTXHIOZUGF-IYBDPMFKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by HTRF assay
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 523.62, ALogP 3.05, HBA 8, HBD 2, PSA 122.75, QED 0.51
Compound (SMILES): Fc1ccc2c(C3CCN(CCCOc4ccc(CN5CCOCC5)c(Cl)c4)CC3)noc2c1
InChIKey: PMQRGOWDOYXFIQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to 5-HT2A receptor (unknown origin)
Measurement: Ki = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 488, ALogP 5.1, HBA 6, HBD 0, PSA 50.97, QED 0.41
Compound (SMILES): Cc1ccc(CN2C(=O)Cc3c(Cl)nc(N)nc32)c(F)c1
InChIKey: FBDCUGDNQVNZDP-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal Grp94 (unknown origin) incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 306.73, ALogP 2.25, HBA 4, HBD 1, PSA 72.11, QED 0.86
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(OC)c(c3)OCCC(=O)COc3cccc2c3)cc1OC
InChIKey: SZOGWFMMFBPZTI-TWBLSBBDSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12 (unknown origin) expressed in Escherichia coli BL21 (DE2) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 743.89, ALogP 7.41, HBA 10, HBD 0, PSA 119.06, QED 0.22
Compound (SMILES): N=C(N)NCCCCC(=O)NCCN1CCC(NC(=O)C(=O)Nc2ccc(Cl)cc2)CC12CCCCC2
InChIKey: NFDAXDYPSSRZOD-UHFFFAOYSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: CD4 mimetic activity at gp120 in HIV-1 KP-5mvcR infected in human TZM-bl cells assessed as inhibition of viral entry by measuring reduction in RLU by single round assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 534.11, ALogP 2.33, HBA 5, HBD 6, PSA 152.44, QED 0.12
Compound (SMILES): COc1ccccc1C1CC1CNCCCOc1ccc2c(c1)NC(=O)CC2
InChIKey: QEUWXRKGMNJLQY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 380.49, ALogP 3.74, HBA 4, HBD 2, PSA 59.59, QED 0.65
Compound (SMILES): Clc1cnc(CNc2cc3sncc3cc2Cl)s1
InChIKey: GFNMKESSHVFPQM-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at human TRPV1 expressed in CHO cells assessed as increase in capsaicin-induced intracellular calcium level measured after 1 hr by FLIPR assay
Measurement: EC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 316.24, ALogP 4.67, HBA 5, HBD 1, PSA 37.81, QED 0.76
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)cc1
InChIKey: XNOMSXYPJLBWKR-VFZGUZRASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 362.36, ALogP -3.14, HBA 8, HBD 6, PSA 179.41, QED 0.33
Compound (SMILES): CN(Cc1cccc(O)c1Cl)C(C1CCCC1)C(F)(F)F
InChIKey: MEDYRJGDKGOLCC-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha S463P mutant (unknown origin) expressed in Escherichia coli preincubated for 15 mins followed by ligand addition and measured after 1 hr by fluorescent polarization assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 321.77, ALogP 4.6, HBA 2, HBD 1, PSA 23.47, QED 0.88