lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(-c4cnn(C)c4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: FACINUDEPGDOCE-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant N-terminal His-tagged full-length human PI3K p120gamma expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 427.51, ALogP 3.44, HBA 7, HBD 1, PSA 94.34, QED 0.54
Compound (SMILES): COc1ccc2ncnc(CCNC(C)=O)c2c1
InChIKey: XIKRGGZCTKMFQJ-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at human MT2 expressed in CHO cell membrane incubated for 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 835 nM (pChEMBL 6.079999923706055)
Descriptors: MW 245.28, ALogP 1.32, HBA 4, HBD 1, PSA 64.11, QED 0.88
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(SCC(=O)Nc3ccc(Cl)cc3)o2)cc1
InChIKey: CXNMCRVIIASCFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 837.6 nM (pChEMBL 6.079999923706055)
Descriptors: MW 424.89, ALogP 2.77, HBA 7, HBD 2, PSA 128.18, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccccc3)s2)cc1
InChIKey: GWTAISADZNYBMN-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX2 from adenosine receptor A2A in rat brain striatum membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 414.49, ALogP 5.3, HBA 5, HBD 1, PSA 68.29, QED 0.43
Compound (SMILES): C[C@@H](c1nc2ccc(Cl)cc2[nH]1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: WGMKPGXMULYDDV-OAGGEKHMSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in recombinant IFN-gamma induced human HeLa cells incubated for 18 hrs by fluorescence microplate reader assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 407.92, ALogP 6.98, HBA 2, HBD 1, PSA 41.57, QED 0.4
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)Nc1ccc(C(=O)O)cc1F
InChIKey: LCFQGSRRJKESSW-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity (B-1A): 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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 479.31, ALogP 6.06, HBA 3, HBD 2, PSA 79.29, QED 0.37
Compound (SMILES): c1cc2cc(-c3ccc4oc(C5=NCCN5)cc4c3)[nH]c2cc1C1=NCCN1
InChIKey: YGJRBLKDKDPKDV-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR22
Assay: Inhibition of recombinant His-tagged human PRMT8 expressed in Escherichia coli BL21 (DE3) using biotin-labeled histone H4-20 peptide as substrate incubated for 8 mins in presence of [3H]-SAM cofactor by scintillation proximity assay
Measurement: IC50 = 60100 nM (pChEMBL 4.21999979019165)
Descriptors: MW 369.43, ALogP 3.28, HBA 5, HBD 3, PSA 77.71, QED 0.52
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)NCCCF)[C@@H](O)[C@H]1O
InChIKey: VEXAKFSPTGBXJQ-QRIDJOKKSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 340.32, ALogP -1.5, HBA 9, HBD 4, PSA 148.41, QED 0.48
Compound (SMILES): O=C(O)CC1CC(=O)N1C(=O)NCc1ccccc1
InChIKey: XTNLRPMBRFOVIZ-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Antagonist activity at alphaVbeta5 in human MCF7 cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 0.97, HBA 3, HBD 2, PSA 86.71, QED 0.79
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)N2CCC[C@@H]2C(=O)NO)cc1)OCc1ccccc1
InChIKey: YHJQUVBJZRCTFG-QGZVFWFLSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 419.46, ALogP 2.09, HBA 6, HBD 3, PSA 125.04, QED 0.49
Compound (SMILES): COc1cc2nccc(Oc3ccc(C(=O)Nc4ccccn4)cc3)c2cc1NC(=O)C#CCCN1CCOCC1
InChIKey: KPZGJWPPVXZLDN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of His-tagged recombinant human His-tagged full length BTK expressed in baculovirus expression system using Tyr01 peptide as substrate preincubated for 1 hr by Z'lyte assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 551.6, ALogP 4.35, HBA 8, HBD 2, PSA 114.91, QED 0.31
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc2c(NC(=O)C(Cc3ccccc3)NC(=O)c3ccccc3)cccc12
InChIKey: GIXYSOPAEGHVQN-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 529.66, ALogP 4.9, HBA 4, HBD 3, PSA 104.37, QED 0.3
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cn2c1-c1cccc(S(C)(=O)=O)c1
InChIKey: TYLDIOXQNAOHRU-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 451.49, ALogP 2.96, HBA 9, HBD 2, PSA 139.06, QED 0.47
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc3cccnc23)CC1
InChIKey: GQUKVOGAZWDTMK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 0.3388 nM (pChEMBL 9.470000267028809)
Descriptors: MW 459.92, ALogP 4.64, HBA 4, HBD 1, PSA 54.46, QED 0.52
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnc4n3CCC4)c(Cl)cn2)C1
InChIKey: OHJQYFCYYWSDGL-UONOGXRCSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (3 nM CDK9/CycT1, 6 μM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 401.9, ALogP 3.18, HBA 5, HBD 2, PSA 88.91, QED 0.82
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCCCC2)ccc1OC(=O)N(c1ccccc1)c1ccccc1
InChIKey: FRTYPMGQTQZTSS-FBMGVBCBSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 27200 nM (pChEMBL 4.570000171661377)
Descriptors: MW 456.54, ALogP 6.06, HBA 4, HBD 0, PSA 59.08, QED 0.42
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cc(Nc3cnn(CCOC)c3)ncn2)cc1
InChIKey: MVKOIQROLYNKGI-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 364.41, ALogP 2.85, HBA 7, HBD 2, PSA 93.96, QED 0.6
Compound (SMILES): Cc1ccc(C(=O)NC2CCCCCC2)c(OCc2ccc(F)cc2)n1
InChIKey: NRGJIFHBRFCUIQ-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using [glycerol-1,2,3-3H]2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 356.44, ALogP 4.56, HBA 3, HBD 1, PSA 51.22, QED 0.8
Compound (SMILES): C/C(=N\NC(=O)c1ccc(S(N)(=O)=O)cc1)c1cc2ccccc2oc1=O
InChIKey: VFJNXTKKJJKNJE-RGVLZGJSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 19.7 nM (pChEMBL 7.710000038146973)
Descriptors: MW 385.4, ALogP 1.59, HBA 6, HBD 2, PSA 131.83, QED 0.4
Compound (SMILES): C[C@@H](O)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)CCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(C)(C)S)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)C(C)(C)C
InChIKey: OBVAHXXYLZOMTI-WWOYFABJSA-N
Target: Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15599
Assay: Binding affinity to NHERF2 PDZ2 domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay
Measurement: Kd = 4070 nM (pChEMBL 5.389999866485596)
Descriptors: MW 2063.43
Compound (SMILES): C[C@]1(c2ccc(F)cc2)CN(C(=O)C2CCN(C(=O)CC#N)CC2)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: JACZDQDBHYAEIU-JYFHCDHNSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at ROR-beta (unknown origin) expressed in Jurkat cells by gal4 reporter assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 599.55, ALogP 5.17, HBA 4, HBD 1, PSA 84.64, QED 0.48
Compound (SMILES): N[C@@H](COP(=O)(O)OCCOC(=O)CCc1ccccc1OCc1cccc(Oc2ccccc2)c1)C(=O)O
InChIKey: ZZXYRMGFBJERKK-DEOSSOPVSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 2290.87 nM (pChEMBL 5.639999866485596)
Descriptors: MW 559.51, ALogP 4.08, HBA 9, HBD 3, PSA 163.84, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#Cc4ccc(C5CC5)s4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: JEUPHUWQEREYNE-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 658.8, ALogP 6.36, HBA 8, HBD 2, PSA 128.17, QED 0.18
Compound (SMILES): O=C(CCN1CCCc2ccccc21)NC1CCCC1
InChIKey: KQRIXGFCTRCLAY-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 245.47 nM (pChEMBL 6.610000133514404)
Descriptors: MW 272.39, ALogP 2.89, HBA 2, HBD 1, PSA 32.34, QED 0.91
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)ccc1OC(=O)N(C)C
InChIKey: YPFUXEHNZQELSW-ZRDIBKRKSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 23500 nM (pChEMBL 4.630000114440918)
Descriptors: MW 423.51, ALogP 3.11, HBA 5, HBD 0, PSA 62.32, QED 0.67
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccccc2)cc1
InChIKey: JWGFBEXNOWIWRP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 40.2 nM (pChEMBL 7.400000095367432)
Descriptors: MW 398.47, ALogP 0.9, HBA 5, HBD 4, PSA 147.46, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(-c5ccncc5)c4)c3n2)cn1
InChIKey: HEAGNKNMQVIVMM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.4, ALogP 4.96, HBA 5, HBD 0, PSA 56.74, QED 0.46
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc(-c3cccnc3)nc2)[nH]1
InChIKey: JBUCEVSQWHDZGD-VPUSJEBWSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 528.7, ALogP 5.35, HBA 6, HBD 2, PSA 103.87, QED 0.31
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)c1ccc2ccccc2c1
InChIKey: LOMJHEAYYYPWDO-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 1,3-dihydroxypropan-2-yl 4-pyren-1-ylbutanoate as substrate measured after 45 mins by reverse-phase HPLC-based fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 315.34, ALogP 2.76, HBA 6, HBD 1, PSA 86.69, QED 0.61
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)CN(CCCNC(=N)N)C(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: YDZQPKRRPVPMCL-NETOACFBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 977.14, ALogP -1.27, HBA 10, HBD 9, PSA 311.42, QED 0.06
Compound (SMILES): Nc1cc(F)c(S(=O)(=O)N2CCC(O)CC2)cc1C(=O)Nc1ccc(F)c(C(F)F)c1
InChIKey: MHCNWGDMXZHYMZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human liver microsome CYP3A4 using sorafenib as substrate incubated for 20 mins by LC-MS/MS with HPLC analysis
Measurement: IC50 = 20800 nM (pChEMBL 4.679999828338623)
Descriptors: MW 461.44, ALogP 2.88, HBA 5, HBD 3, PSA 112.73, QED 0.47
Compound (SMILES): COC(=O)CC[C@H]1[C@@H]2CCC[C@@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: NIGWAKMPTZHINX-GNKBHMEESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Activity at human MOR expressed in U2OS cells co-expressing beta-arrestin2 EFC assessed as beta-arrestin2 EFC recruitment by Tango assay
Measurement: EC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 407.55, ALogP 4.7, HBA 4, HBD 1, PSA 49.77, QED 0.68
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCCc2ccccc2)CC1
InChIKey: MXCJGJFHRSTAIG-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 = 446.68 nM (pChEMBL 6.349999904632568)
Descriptors: MW 406.9, ALogP 4.65, HBA 2, HBD 1, PSA 32.34, QED 0.68
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: FYAXJKADJJRRRN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 834.1, ALogP 8.14, HBA 7, HBD 2, PSA 106.69, QED 0.06
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1cncc(F)c1
InChIKey: QLWGSXWLXIBFPF-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 392.37, ALogP 3.12, HBA 8, HBD 2, PSA 118.33, QED 0.55
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4)c(Cl)cn2)C1
InChIKey: AKIBGBJFUGFCIJ-LSDHHAIUSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant full length human CDK7/cyclinH1/MAT1 expressed in insect cells using 5FAM-YSPTSPSYSPTSPSYSPTSPSKKKK-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 120 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 415.93, ALogP 3.57, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NCC(CCCC(=O)O)c1ccccc1Cl
InChIKey: ZIDVHLLOHYVUEZ-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 30 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 multititre plate (from Greiner, TC plate, black with clear base) and incubated at 33° 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, 6.3 mM Probenecid, 5 μM Fluo-8 AM, 0.0112% Pluronic®] 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, 0.002% SmartBlock (from CANDOR Bioscience GmbH). 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 40 μl of 2 nM (final concentration) PGF2α in calcium-free Tyrode, 2 mM CaCl2, 0.002% SmartBlock, 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 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 565.9, ALogP 7.39, HBA 3, HBD 2, PSA 79.29, QED 0.22
Compound (SMILES): COc1cc(CNC(=O)CCCCCCNc2c3c(nc4cc(Cl)ccc24)CC2C=C(C)CC3C2)ccc1O
InChIKey: JGUYMIZRMYBDGV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed-type inhibition of recombinant human AChE assessed as inhibition constant using acetylthiocholine iodide as substrate by Cornish-Bowden plot analysis
Measurement: Ki = 0.68 nM (pChEMBL 9.170000076293945)
Descriptors: MW 548.13, ALogP 7.28, HBA 5, HBD 3, PSA 83.48, QED 0.17
Compound (SMILES): Cn1ncc(-c2nc(N[C@H]3CC[C@H](N)CC3)ncc2Cl)c1CC1CC1
InChIKey: RVZJFCNYSSUDCU-JOCQHMNTSA-N
Target: Casein kinase I isoform alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48729
Assay: Inhibition of CSNK1A1 (unknown origin)
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 360.89, ALogP 3.16, HBA 6, HBD 2, PSA 81.65, QED 0.86
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(C)(=O)=O)CC3)cc2)nc2sccc12
InChIKey: QHIRMUBXJDXTRL-SNAWJCMRSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 1952 nM (pChEMBL 5.710000038146973)
Descriptors: MW 560.71, ALogP 5.46, HBA 9, HBD 1, PSA 111.45, QED 0.3
Compound (SMILES): COc1ccc2cc([C@H](C)C(=O)Nc3cc(C)ccn3)ccc2c1
InChIKey: QUOGFPPPCZTQAX-AWEZNQCLSA-N
Target: SNF-related serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRH2
Assay: Inhibition of recombinant human SNRK E97G/P116A mutant (1 to 505 residues) using KKLRRTLSFAEPG peptide as substrate incubated for 40 mins in presence of [gamma33P]ATP by radiometric scintillation analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 320.39, ALogP 4.29, HBA 3, HBD 1, PSA 51.22, QED 0.78
Compound (SMILES): Cc1ccc(NC(=O)c2n[nH]c3ccc(-c4cncc(CN5CCCCC5)c4)cc23)cn1
InChIKey: HVEOEVJLUUUHNZ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin) by FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 426.52, ALogP 4.57, HBA 5, HBD 2, PSA 86.8, QED 0.49
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]nc(F)c23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)F
InChIKey: XFDBWZWHJOLNAF-DMZKTXOQSA-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 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 512.5, ALogP 4.59, HBA 5, HBD 2, PSA 60.08, QED 0.45
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C)CC2
InChIKey: FKFTVEPJIOFORF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Enzymatic Activity Assay: The enzymatic activity of Wild Type HPK1 (MAP4K1) Kinase was measured in the presence or absence of an inhibitor compound of the present disclosure by preparation of a reaction mixture containing a fluorescein tagged peptide (2 micromolar final concentration), ATP (Adenosine Triphosphate, 500 micromolar final concentration) and Wild Type kinase (6 nM final concentration) in a buffer system comprising 50 mM HEPES (Buffer), 3 mM MgCl2, 5% w/v Trehalose, 0.01% Brij 35 (Detergent), 0.1% Pluronic F127 (Surfactant), 0.1 mM EDTA (Ethylenediaminetetraacetic acid), 0.1 mM EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid) and 1 mM DTT (Dithiothreitol) and at a pH of 7.4. The reactions were quenched by the addition of EDTA to a final concentration of 25 mM. A Caliper EZ reader was used to measure the extent of substrate to product conversion.The peptide substrate used in the HPK1 assay was designed based on the amino acid sequence surrounding serine residue 376 of SLP76-Lymphocyte cytosolic protein 2 (a known intracellular substrate of HPK1). This sequence SSFPQSAsLPPYFSQ was modified as follows for use in Caliper assays of HPK1: the serine residues on either side of serine 376 were replaced with alanine, three lysine residues were added at the N-terminus and a fluorescein tag (FAM) was attached to the C-terminus to produce the sequence, FAM-FPQAAsLPPYFAKKK.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 502.04, ALogP 4.8, HBA 8, HBD 2, PSA 96.45, QED 0.48
Compound (SMILES): Oc1ccc(CNc2ccc(O)c(O)c2)cc1O
InChIKey: BOLQVOXQHFRJPR-UHFFFAOYSA-N
Target: Arginase-1 (SINGLE PROTEIN), Bos taurus
UniProt: Q2KJ64
Assay: Mixed type inhibition of recombinant bovine liver ARGI using L-arginine as substrate incubated for 60 mins by Cornish-Bowden plot analysis
Measurement: Ki = 82000 nM (pChEMBL 4.090000152587891)
Descriptors: MW 247.25, ALogP 2.12, HBA 5, HBD 5, PSA 92.95, QED 0.42
Compound (SMILES): CCOc1ncc(-c2cnc([C@H](CCCCCC(=O)CC)NC(=O)[C@H]3CC34CCN(C)CC4)[nH]2)cn1
InChIKey: UKBZWOAYQVHEBM-YADHBBJMSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 583 nM (pChEMBL 6.230000019073486)
Descriptors: MW 496.66, ALogP 4.08, HBA 7, HBD 2, PSA 113.1, QED 0.4
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C(C)(C)C)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: HDZRQPPPUOILEX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 463.61, ALogP 5.28, HBA 9, HBD 1, PSA 82.68, QED 0.43
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)F
InChIKey: LCCYGLSQPCXNFG-MYYSRTQBSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 458.53, ALogP 4.01, HBA 5, HBD 2, PSA 60.08, QED 0.53
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: QQGKDRSESGQPHS-FQEVSTJZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 25.9 nM (pChEMBL 7.590000152587891)
Descriptors: MW 439.54, ALogP 3.74, HBA 5, HBD 2, PSA 101.88, QED 0.52
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c(=O)c32)C1
InChIKey: QUYXPVXTKPTPCA-QGZVFWFLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome CYP2C9 using diclofenac as substrate preincubated for 10 mins followed by substrate and NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 39600 nM (pChEMBL 4.400000095367432)
Descriptors: MW 456.51, ALogP 3.51, HBA 7, HBD 2, PSA 119.13, QED 0.44
Compound (SMILES): COC(=O)/C=C/CN1CCc2cc(Nc3ncc(C)c(-c4cnn(C(C)C)c4)n3)ccc2C1
InChIKey: VBNPFKOUEKQSDK-AATRIKPKSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 446.56, ALogP 4.06, HBA 8, HBD 1, PSA 85.17, QED 0.43
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(O[C@@H]2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: DMUSMYYDKCXFKR-MRJIRHQNSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of human recombinant CDK12/CyclinK assessed as reduction in substrate phosphorylation using His-c-Myc as substrate preincubated with enzyme for 5 mins followed by substrate addition for 15 mins in presence of [gamma 32P-ATP] by radioactive kinase assay
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 545.09, ALogP 6.14, HBA 6, HBD 3, PSA 95.17, QED 0.22
Compound (SMILES): Cc1cc(Nc2ccc3ncccc3c2)nc(-c2ccccc2)n1
InChIKey: OHTBOWYUOVCMTB-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of human ABCB1-mediated multidrug resistance in human A2780/ADR cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring half maximal reversal concentration after 72 hrs by MTT assay
Measurement: EC50 = 8410 nM (pChEMBL 5.079999923706055)
Descriptors: MW 312.38, ALogP 4.74, HBA 4, HBD 1, PSA 50.7, QED 0.59
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@](C)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: WNRMDDVUGJBHGZ-QFIPXVFZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 456.55, ALogP 2.16, HBA 10, HBD 2, PSA 131.62, QED 0.71
Compound (SMILES): O=C(Cc1ccc2ccccc2c1)Nc1cc(Cl)ccn1
InChIKey: UPVVKGJGCKBECE-UHFFFAOYSA-N
Target: SNF-related serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRH2
Assay: Inhibition of recombinant human SNRK E97G/P116A mutant (1 to 505 residues) using KKLRRTLSFAEPG peptide as substrate incubated for 40 mins in presence of [gamma33P]ATP by radiometric scintillation analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 296.76, ALogP 4.07, HBA 2, HBD 1, PSA 41.99, QED 0.79
Compound (SMILES): O=C1c2ccc([N+](=O)[O-])cc2C(=O)C1(O)O
InChIKey: CKNXPOACSQXSGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 29600 nM (pChEMBL 4.53000020980835)
Descriptors: MW 223.14, ALogP -0.35, HBA 6, HBD 2, PSA 117.74, QED 0.29
Compound (SMILES): O=C(c1ccc(Cl)c(Cl)c1)N1CCC(F)(CNCCOc2ccccn2)CC1
InChIKey: LBGPXUXLKXFCMK-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 = 173.78 nM (pChEMBL 6.760000228881836)
Descriptors: MW 426.32, ALogP 4, HBA 4, HBD 1, PSA 54.46, QED 0.68
Compound (SMILES): CO[C@@]12CC[C@H](N[C@@H](Cc3ccccc3)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: SILMEZJWWQTRJT-KTUZKFFASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 464.56, ALogP 2.48, HBA 6, HBD 3, PSA 91.26, QED 0.61
Compound (SMILES): N#Cc1cnc(Nc2cc(NC[C@H]3CNCCO3)c(Cl)cn2)cn1
InChIKey: BSNBUKMEBPSBIJ-LLVKDONJSA-N
Target: Cytochrome P450 2A6 (SINGLE PROTEIN), Homo sapiens
UniProt: P11509
Assay: Inhibition of CYP2A6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.79, ALogP 1.54, HBA 8, HBD 3, PSA 107.78, QED 0.75
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: FXBTWOVLKURNIB-VGXZEHLRSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 980.19, ALogP -2.73, HBA 12, HBD 16, PSA 416.84, QED 0.02
Compound (SMILES): CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O
InChIKey: HSJMNXXZYVFSJQ-PSWJWLENSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse melanocortin receptor 4 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: Ki = 320 nM (pChEMBL 6.5)
Descriptors: MW 734.86, ALogP 1.04, HBA 7, HBD 8, PSA 241.28, QED 0.05
Compound (SMILES): CC(=O)Nc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: YNHCYBQECNBQLO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 21.88 nM (pChEMBL 7.659999847412109)
Descriptors: MW 465.93, ALogP 4.05, HBA 4, HBD 2, PSA 70.67, QED 0.58
Compound (SMILES): Fc1ccc(CNc2nc(/C=C/c3ccccc3)nc3cc(-c4cccs4)ccc23)cc1F
InChIKey: NYRKGXAEURPTHL-UKTHLTGXSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Competitive inhibition of ovine COX-1 assessed as reduction in PGE2 production using 6250 nM arachidonic acid as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured after 20 mins by ELISA
Measurement: IC50 = 254 nM (pChEMBL 6.590000152587891)
Descriptors: MW 455.53, ALogP 7.42, HBA 4, HBD 1, PSA 37.81, QED 0.29
Compound (SMILES): CC(C)Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCCCCCCC(=O)NO)cc12
InChIKey: ZPZTZOURCDUBLM-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) by fluorescence based assay
Measurement: IC50 = 36.4 nM (pChEMBL 7.440000057220459)
Descriptors: MW 526.63, ALogP 3.73, HBA 7, HBD 5, PSA 145.68, QED 0.14
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-AXSFQXJPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 2.52 nM (pChEMBL 8.600000381469727)
Descriptors: MW 503.6, ALogP 2.97, HBA 6, HBD 4, PSA 107.05, QED 0.41
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(C2=CC(=O)N(C)CC2)[nH]1
InChIKey: ASZVTDQFKPAJLA-YADHBBJMSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 1664 nM (pChEMBL 5.78000020980835)
Descriptors: MW 483.66, ALogP 3.47, HBA 5, HBD 2, PSA 98.4, QED 0.47
Compound (SMILES): C[C@]1(c2ccc(F)cc2)CN(C(=O)NCc2ccccc2)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: VZZQWPNMECGJBM-UKILVPOCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: SPA Binding Assay: The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM for 10 min at room temperature in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% Glycerol (Sigma Cat # G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined.
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 554.51, ALogP 6.4, HBA 2, HBD 2, PSA 52.57, QED 0.36
Compound (SMILES): COC[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: CASGKNKGRHYUAE-ZWKOTPCHSA-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 = 100000 nM (pChEMBL 4)
Descriptors: MW 420.95, ALogP 1.97, HBA 7, HBD 2, PSA 92.53, QED 0.74
Compound (SMILES): COc1ccc(Cl)cc1NC(=O)Nc1ccc2nc(NC(=O)c3ccccc3)sc2c1
InChIKey: GFYCKNKAOMHFQF-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human TRKA at active state assessed as inhibition of substrate phosphorylation using fluorescently-labelled peptide as substrate by caliper assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 452.92, ALogP 5.85, HBA 5, HBD 3, PSA 92.35, QED 0.35
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@@H]4CCN(c5ccncc5)C4)nc32)cc1
InChIKey: GDSSVNNRCKMPPZ-CQSZACIVSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of ERK3 (unknown origin) expressed in HEK293 cells cotransfected with nano-luciferase by NanoBRET assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 388.44, ALogP 2.3, HBA 9, HBD 1, PSA 93.88, QED 0.56
Compound (SMILES): Cn1nc(-c2ccc(OCCCC3CCNCC3)c(F)c2)c2cnc(N)nc21
InChIKey: YSLSSCOTQRLGCR-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at TLR9 in human PBMC assessed as inhibition of ODN2216-induced IFNalpha production
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 384.46, ALogP 2.91, HBA 7, HBD 2, PSA 90.88, QED 0.64
Compound (SMILES): CN(C)CCNc1cc(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)ccn1
InChIKey: TXVXRKMYWIBEFX-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologies-a Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% Control") and phosphorylated ("100% control") forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 415.5, ALogP 3.26, HBA 7, HBD 2, PSA 87.97, QED 0.48
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCCC(NS(N)(=O)=O)C3)cc2)nc2ccsc12
InChIKey: LFOHHWYSEIPYJS-HWKANZROSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 381 nM (pChEMBL 6.420000076293945)
Descriptors: MW 575.72, ALogP 5.14, HBA 9, HBD 3, PSA 146.26, QED 0.24
Compound (SMILES): Nc1nc2sc(CCCCc3csc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c3)cc2c(=O)[nH]1
InChIKey: QNFVXICXLFWABV-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 = 8030 nM (pChEMBL 5.090000152587891)
Descriptors: MW 478.55, ALogP 2.24, HBA 8, HBD 5, PSA 175.47, QED 0.26
Compound (SMILES): CNC(=O)COc1cc2cc(Nc3nc(N4CCC(C(=O)N(C)C)CC4)ncc3Cl)cc(OC)c2n(C)c1=O
InChIKey: XCGYXEVLQIIEJH-UHFFFAOYSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: BCL6::NCOR LUMIER in cells
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 558.04, ALogP 2.16, HBA 10, HBD 2, PSA 130.92, QED 0.43
Compound (SMILES): COc1cc(F)ccc1-c1cc(NC(=O)[C@H]2CCC[C@@H](NC(C)=O)C2)ncc1Cl
InChIKey: YWKHYOGNLAAFGK-DZGCQCFKSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin)
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 419.88, ALogP 4.18, HBA 4, HBD 2, PSA 80.32, QED 0.76