lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCC(C)Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: PETSAMLQOBIHSS-PIJUOVFKSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 90 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 394.45, ALogP 4.76, HBA 6, HBD 2, PSA 75.62, QED 0.67
Compound (SMILES): CCN(CC)CC.CCN(CC)CC.O=c1ccn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]2O)c(=O)[nH]1
InChIKey: YUACGYFLUWHTNV-WFIJOQBCSA-N
Target: P2Y purinoceptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15077
Assay: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as induction of calcium mobilization by FLIPR method
Measurement: EC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 404.16, ALogP -2.62, HBA 10, HBD 6, PSA 217.84, QED 0.27
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cn(S(C)(=O)=O)cn3)CC2)nc2ccsc12
InChIKey: MAZUVMQRDUXXOS-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 3B reverse transcriptase infected in human MT4 cells assessed as protection against virus-induced cytotoxicity by MTT assay
Measurement: EC50 = 5.67 nM (pChEMBL 8.25)
Descriptors: MW 537.67, ALogP 4.05, HBA 11, HBD 1, PSA 126.03, QED 0.37
Compound (SMILES): Cc1noc(C)c1-c1ccc2nc(C(=O)N3CCN(CCN(C)C)CC3)nc(NCc3cccc(Cl)c3)c2c1
InChIKey: MTVZOLGJCRFKMK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated acetylated peptide from recombinant human partial length BRD4 long isoform bromodomain 1/2 (N44 to E460 residues) expressed in Escherichia coli BL21 measured after 1 hr by Bromoscan method
Measurement: Kd = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 548.09, ALogP 4.49, HBA 8, HBD 1, PSA 90.63, QED 0.35
Compound (SMILES): Cc1ccc(OCc2ccccn2)c(-c2ccccc2)n1
InChIKey: RRXFOMLDAZJMHW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of recombinant human N-terminal His6-tagged SYK expressed in baculovirus expression system using Biotin-AAAEEIYGEI as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 276.34, ALogP 4.03, HBA 3, HBD 0, PSA 35.01, QED 0.72
Compound (SMILES): O=c1[nH]c(SCCCc2ccccc2)nc2ccccc12
InChIKey: RKBZXWJOXHLBLV-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using kynuramine as substrate after 20 mins by fluorescence spectrophotometric analysis
Measurement: IC50 = 5990 nM (pChEMBL 5.21999979019165)
Descriptors: MW 296.39, ALogP 3.65, HBA 3, HBD 1, PSA 45.75, QED 0.44
Compound (SMILES): O=C(Nc1cc(C(F)F)ns1)Nc1cc(F)ncc1CO
InChIKey: CKYCAIAVJIFWPE-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 318.28, ALogP 2.75, HBA 5, HBD 3, PSA 87.14, QED 0.76
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3csc(C(F)(F)F)n3)n2)CC1
InChIKey: PFTFOLWIPCINKJ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132H mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presence of NADPH and 30 uM NADP ny fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 498.47, ALogP 5.99, HBA 7, HBD 2, PSA 75.62, QED 0.49
Compound (SMILES): CS(=O)(=O)c1ccc(-n2nc(-c3ccc(-c4ccccc4)cc3)c3ccccc3c2=O)cc1
InChIKey: ZVLXLXFJTHOHIF-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin)
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 452.54, ALogP 5.12, HBA 5, HBD 0, PSA 69.03, QED 0.38
Compound (SMILES): COc1cc2nc(N3CCCCC3)nc(NC3CCN(Cc4cccc(F)c4)CC3)c2cc1OC
InChIKey: WGZBJGADOHTBDB-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of human G9a using biotinylated peptide H3( 1 to 25 residues) as substrate measured after 15 mins in presence of [3H]-SAM by scintillation proximity assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 479.6, ALogP 4.85, HBA 7, HBD 1, PSA 62.75, QED 0.52
Compound (SMILES): COc1ccc([C@H]2C[C@@H]3CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H]([C@H](C)C[C@@H]3CC[C@@H](O)[C@H](OC)C3)CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C/2C)c(OC)c1
InChIKey: GSJHOKJUKNLENH-BUGBDXMFSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Inhibition of recombinant human FKBP12 expressed in Escherichia coli using succinyl-Ala-Phe-Pro-Phe-4-nitroanilide as substrate measured after 5 to 10 mins by spectrophotometric method
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 1020.31
Compound (SMILES): O=C(CCC(CCCC(=O)Nc1ccccc1)c1ccccc1)NO
InChIKey: CKQYXRXVDRHVDK-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 in human HeLa-S3 cell lysates preincubated for 15 mins followed by HDAC-Glo substrate addition measured after 30 to 40 mins by fluorimetric method
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 340.42, ALogP 3.86, HBA 3, HBD 3, PSA 78.43, QED 0.48
Compound (SMILES): C#CCNc1nc(NCCCC2CCN(Cc3ccccc3)CC2)c(C#N)cc1C#N
InChIKey: QDTPLCGSZPKZME-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 412.54, ALogP 3.97, HBA 6, HBD 2, PSA 87.77, QED 0.48
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2cc(C(=O)O)ccc2F)c2ccccc12
InChIKey: PRQVEVLBUCMWDD-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of 1,8-ANS from FABP4 (unknown origin) after 3 mins by fluorescence assay
Measurement: IC50 = 1650 nM (pChEMBL 5.78000020980835)
Descriptors: MW 375.38, ALogP 3.49, HBA 4, HBD 2, PSA 92.7, QED 0.71
Compound (SMILES): O=C(CCN1CCN(c2ncccn2)CC1)c1cc2c3c(c1)CCC(=O)N3CCC2
InChIKey: XMAJZXPBSHQXFR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Displacement of [3H]-8-OH-DPAT from serotonin 5-HT1A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 1965.4 nM (pChEMBL 5.710000038146973)
Descriptors: MW 405.5, ALogP 2.1, HBA 6, HBD 0, PSA 69.64, QED 0.71
Compound (SMILES): Cc1oncc1Cn1c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc2n(C)c1=O
InChIKey: PGUIAJMBTFAXFK-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 404.45, ALogP 0.88, HBA 8, HBD 1, PSA 116.2, QED 0.67
Compound (SMILES): CCOc1ccc(-c2cc(C(=O)c3ccccc3)c3ccc(C(=O)O)ccc2-3)cc1
InChIKey: UDMKMROCQZKCTL-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1 receptor expressed in CHOK1 cells assessed as inhibition of orexin-A-induced calcium accumulation preincubated for 30 mins followed by orexin-A addition measured for 150 secs by calcium-4 dye based FLIPR assay
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 396.44, ALogP 5.79, HBA 3, HBD 1, PSA 63.6, QED 0.42
Compound (SMILES): O=C(Cc1cccc(Cl)c1)c1ccc(O)c(O)c1O
InChIKey: HAZQRXQNHINBAP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha H1047R mutant (unknown origin) by HTRF assay
Measurement: EC50 = 98200 nM (pChEMBL 4.010000228881836)
Descriptors: MW 278.69, ALogP 2.88, HBA 4, HBD 3, PSA 77.76, QED 0.6
Compound (SMILES): O=C(c1ccc(OC(F)(F)F)c(Cl)c1)N1CC(OCc2ccc(S(=O)(=O)Nc3ncns3)cc2)C1
InChIKey: ADOWSVOCFBZXBB-UHFFFAOYSA-N
Target: Sodium channel protein type 3 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY46
Assay: Inhibition of human NaV1.3 expressed in HEK cells by electrophysiological method
Measurement: IC50 = 237 nM (pChEMBL 6.619999885559082)
Descriptors: MW 548.95, ALogP 3.93, HBA 8, HBD 1, PSA 110.72, QED 0.45
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3cccc(F)c3)CC2)cc(C(C)(C)C)c1O
InChIKey: CTWWCIRKFWZLQA-ZHACJKMWSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine chloride as substrate incubated for 5 mins followed by substrate addition measured after 180 secs by Ellman's method
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 494.7, ALogP 6.56, HBA 3, HBD 2, PSA 52.57, QED 0.43
Compound (SMILES): COc1c(Br)cccc1C(=O)Nc1cccc(Cl)c1
InChIKey: AWKNDZLXBMJPJB-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coli DH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured MDH refolding after 20 to 40 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.6, ALogP 4.36, HBA 2, HBD 1, PSA 38.33, QED 0.9
Compound (SMILES): CC1=C(C(=O)OC2CCCCC2)C(c2ccc3c(c2)OCCO3)C2=C(CC(C)(C)CC2=O)N1
InChIKey: GRGUUJYIFXXNQN-UHFFFAOYSA-N
Target: Neurogenic locus notch homolog protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P46531
Assay: Inhibition of Notch1 deltaE mutant (unknown origin) expressed in HEK293 cells after 16 hrs by resazurin dye-based luciferase reporter gene assay
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 451.56, ALogP 4.94, HBA 6, HBD 1, PSA 73.86, QED 0.66
Compound (SMILES): CN(C)[C@H]1CC[C@H](Nc2ncnc3ccoc23)CC1
InChIKey: IFYSFPVXYWZNCU-XYPYZODXSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length His-tagged human IRAK4 expressed in baculovirus expression system using 5-FAM-IPTSPITTTYFFFKKK-COOH as substrate after 240 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 4080 nM (pChEMBL 5.389999866485596)
Descriptors: MW 260.34, ALogP 2.51, HBA 5, HBD 1, PSA 54.19, QED 0.92
Compound (SMILES): CC1CC(C(=O)Nc2nc3ccc(Cl)cc3s2)CC(C)(C)C1
InChIKey: NLJWGMYYULUAFJ-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 336.89, ALogP 5.35, HBA 3, HBD 1, PSA 41.99, QED 0.8
Compound (SMILES): COCCc1ccnc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: IIDRMKULCOPTDM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 483.51, ALogP 4.5, HBA 8, HBD 2, PSA 97.74, QED 0.53
Compound (SMILES): C[C@@H](Nc1nc(NC2CCc3ccccc32)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: SNCVLWHFGQJUFT-FWJOYPJLSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 440.47, ALogP 5.26, HBA 6, HBD 2, PSA 75.62, QED 0.54
Compound (SMILES): O=C(c1ccc(-c2ccc(O)cc2)s1)c1cc(F)c(F)c(O)c1F
InChIKey: JALWXIABVXDUPN-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 350.32, ALogP 4.47, HBA 4, HBD 2, PSA 57.53, QED 0.54
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3cnn(C4CCNCC4)c3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: VHIPJRRFLDFKSD-CUWPLCDZSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) using 5'-FAM-KKKKEEIYFFF-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 451.62, ALogP 4.3, HBA 8, HBD 3, PSA 92.82, QED 0.5
Compound (SMILES): CCOC(=O)Nc1oc2c(C#Cc3ccc(C(N)=O)cc3)nccc2c1N(C(=O)OCC)c1ccc(F)c(Cl)c1
InChIKey: BIIQPUDVZKWHPL-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 564.96, ALogP 5.98, HBA 7, HBD 2, PSA 136.99, QED 0.27
Compound (SMILES): COc1ccccc1-c1ccc(C(=O)c2cc(F)c(F)c(O)c2F)s1
InChIKey: CLIKNSSSHWQRMI-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 364.34, ALogP 4.78, HBA 4, HBD 1, PSA 46.53, QED 0.54
Compound (SMILES): COc1ccc(-c2ncc3c(c2F)-c2[nH]c4c(c2CC3)C(=O)NCC42CN(C)C2)cn1
InChIKey: LTPHDFADTLLZOP-UHFFFAOYSA-N
Target: MAP kinase-activated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49137
Assay: Inhibition of human MK2 using hsp27 peptide biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by TR-FRET assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 419.46, ALogP 2.31, HBA 5, HBD 2, PSA 83.14, QED 0.67
Compound (SMILES): C=C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4ccccc34)n2)c(OCC)cc1N(C)CCN(C)C
InChIKey: DCTSDRYEGNUJAC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human EGFR T790M/L858R double mutant (696 to end residues) using poly(Glu, Tyr) 4 : 1 as substrate after 1 hr by ELISA
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 525.66, ALogP 5.06, HBA 8, HBD 2, PSA 87.55, QED 0.21
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCN(Cc3ccccc3)Cc3cn(CCOCCOc4ccc(-c5cc(=O)c6cc(F)ccc6o5)cc4)nn3)ccc12
InChIKey: UCQGLPGXMPPVIB-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) transfected in HEK293/R2 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 778.84, ALogP 8.14, HBA 11, HBD 0, PSA 122.06, QED 0.08
Compound (SMILES): O=C(O)[C@H]1[C@H](c2ccccc2)[C@H](C(=O)OCc2ccccc2)[C@H]1c1ccccc1
InChIKey: MOGDSIWEUDLNRF-MLCQCVOFSA-N
Target: Fatty acid-binding protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01469
Assay: Displacement of DAUDA from recombinant human N-terminal His-tagged FABP5 expressed in Escherichia coli BL21(DE3) after 20 mins by fluorescence assay
Measurement: Ki = 3810 nM (pChEMBL 5.420000076293945)
Descriptors: MW 386.45, ALogP 4.63, HBA 3, HBD 1, PSA 63.6, QED 0.63
Compound (SMILES): C#CCSc1nc2ccccc2c(=O)n1-c1ccccc1
InChIKey: DNSCLWJDGOJUHA-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha production using arachidonic acid as substrate by colorimetric method
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 292.36, ALogP 3.11, HBA 4, HBD 0, PSA 34.89, QED 0.42
Compound (SMILES): CCOc1ccc(Nc2cc(NC(=O)c3ccccc3)ncn2)cc1
InChIKey: HOWQTNUTPZLICX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR del 747-750 mutant cytoplasmic domain expressed in baculovirus expression system using FAM-labeled peptide as substrate after 10 mins by mobility shift assay
Measurement: IC50 = 754 nM (pChEMBL 6.119999885559082)
Descriptors: MW 334.38, ALogP 3.87, HBA 5, HBD 2, PSA 76.14, QED 0.72
Compound (SMILES): CCCCC1NCCc2cc(-c3nc4c(C(N)=O)cc(F)cc4[nH]3)sc21
InChIKey: SNKAWMAERQERAY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human PARP1 using histone as substrate after 1 hr in presence of NAD+ by ELISA
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 372.47, ALogP 3.91, HBA 4, HBD 3, PSA 83.8, QED 0.63
Compound (SMILES): C=C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4ccccc34)n2)c(OC)cc1O[C@H]1CCOC1
InChIKey: NVVVBYLPMCOMTD-SFHVURJKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of Wild type human EGFR using poly(Glu, Tyr) 4 : 1 as substrate after 1 hr by ELISA
Measurement: IC50 = 29.1 nM (pChEMBL 7.539999961853027)
Descriptors: MW 497.56, ALogP 4.83, HBA 8, HBD 2, PSA 99.53, QED 0.27
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3ccccc3Cl)CC2)cc(C(C)(C)C)c1O
InChIKey: IXKCDKJHBGONNW-VAWYXSNFSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine chloride as substrate incubated for 5 mins followed by substrate addition measured after 180 secs by Ellman's method
Measurement: IC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 511.15, ALogP 7.07, HBA 3, HBD 2, PSA 52.57, QED 0.39
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCc3cccc4ccccc34)cn2)c1
InChIKey: HJHPUQDFLVHFFZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 343.39, ALogP 4.04, HBA 4, HBD 1, PSA 68.01, QED 0.59
Compound (SMILES): CS(=O)(=O)N(Cc1ccco1)CC(O)Cn1c2ccccc2c2cc(F)ccc21
InChIKey: ZNHOAEYAGZFLBS-UHFFFAOYSA-N
Target: Cryptochrome-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16526
Assay: Modulation of C-terminal FLAG3-taged CRY1 (unknown origin) expressed in HEK293 cells incubated for 24 hrs measured every 7.5 mins for 1 hr by luciferase reporter gene assay
Measurement: EC50 = 7350 nM (pChEMBL 5.130000114440918)
Descriptors: MW 416.47, ALogP 3.35, HBA 5, HBD 1, PSA 75.68, QED 0.5
Compound (SMILES): CN(C)[C@H]1CC[C@H](Nc2ncnn3ccc([C@H]4CC[C@@H](C(N)=O)CC4)c23)CC1
InChIKey: BGBIYRFKZBBZMB-DSPLQEQRSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length His-tagged human IRAK4 expressed in baculovirus expression system using 5-FAM-IPTSPITTTYFFFKKK-COOH as substrate after 240 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 7762.47 nM (pChEMBL 5.110000133514404)
Descriptors: MW 384.53, ALogP 2.77, HBA 6, HBD 2, PSA 88.55, QED 0.83
Compound (SMILES): NS(=O)(=O)c1ccc(-c2conc2-c2ccccc2)cc1
InChIKey: DLCFBVIPGPNHMB-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 assessed as reduction of prostaglandin-G2 to prostaglandin-H2 by measuring oxidation of 10-acetyl-3,7-dihydroxyphenoxazine to resorufin after 5 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 300.34, ALogP 2.66, HBA 4, HBD 1, PSA 86.19, QED 0.81
Compound (SMILES): Cc1cc(OCCCCN2CCN(c3ccccc3F)CC2)c2c(C)cc(=O)oc2c1
InChIKey: PQMPCPLBZWPBBR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor expressed in CHOK1 cell membranes after 60 mins by microbeta scintillation counting method
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 424.52, ALogP 4.53, HBA 5, HBD 0, PSA 45.92, QED 0.41
Compound (SMILES): C/N=C(/NCCCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(N)=O)N(C)C
InChIKey: DTNIJMWZXRUYPC-XYPUQJIVSA-N
Target: Pyroglutamylated RF-amide peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P65
Assay: Antagonist activity at human QRFPR expressed in CHO cells co-expressing Galpha16 assessed as inhibition of 26RFa-induced Ca2+ mobilization preincubated for 15 mins followed by agonist addition measured after 3 mins by Fluo-4 AM-based scanning fluorometery
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 872.04, ALogP -2, HBA 10, HBD 10, PSA 291.57, QED 0.03
Compound (SMILES): Cc1cccc(Cn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)c1F
InChIKey: LGVMSGMOXACFLZ-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 334.36, ALogP 3.23, HBA 5, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): Nc1sc2ccc(Cl)cc2c1Nc1ccc(F)cc1
InChIKey: ZAERAUPGIBHWPQ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 292.77, ALogP 5.02, HBA 3, HBD 2, PSA 38.05, QED 0.7
Compound (SMILES): C[C@@H](C(=O)N(Cc1ccc(C2CCCCC2)cc1)c1ccc(C(=O)O)cc1)N(C)S(=O)(=O)c1c(F)c(F)c(F)c(F)c1F
InChIKey: AEPZRPYBBQPTFL-KRWDZBQOSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: In Vitro Assay: Nuclear extract preparations and DNA-binding activity/electrophoretic mobility shift assay (EMSA) were carried out as previously described (Zhang X, et al., (2010) Biochem Pharmacol 79:1398-409; Zhang X, et al., (2012) Proc Natl Acad Sci USA 109:9623-8). The 32P-labeled oligonucleotide probes used were hSIE (high affinity sis-inducible element from the c-fos gene, m67 variant, 5′-AGCTTCATTTCCCGTAAATCCCTA) (SEQ ID NO: 1) that binds Stat1 and Stat3 and MGFe (mammary gland factor element from the bovine β-casein gene promoter, 5′-AGATTTCTAGGAATTCAA) (SEQ ID NO: 2) for Stat1 and Stat5 binding. Except where indicated, nuclear extracts were pre-incubated with compound for 30 min at room temperature prior to incubation with the radiolabeled probe for 30 min at 30° C. before subjecting to EMSA analysis. Where appropriate, bands corresponding to Stat3:DNA complexes were scanned and quantified for each concentration of compound using ImageJ and plotted as percent of control (DMSO) against concentration of compound, from which the IC50 values were derived.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 624.63, ALogP 6.37, HBA 4, HBD 1, PSA 94.99, QED 0.17
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1CN(C(=O)c2cccc(C#N)c2)CC12CC2
InChIKey: BSLBVTSKCBBAKT-KRWDZBQOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate after 40 mins in presence of [gamma-33P-ATP] by scintillation counting method
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 372.43, ALogP 2.57, HBA 5, HBD 1, PSA 88.91, QED 0.76
Compound (SMILES): CC(Nc1nc(Nc2ccnc(C3(C#N)CC3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: HJCRKYCQHOQKKS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presence of NADPH and 30 uM NADP ny fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 494.4, ALogP 5.01, HBA 8, HBD 2, PSA 112.3, QED 0.46
Compound (SMILES): COc1ccc(-c2cc(CSc3nc4ccccc4c(=O)n3-c3ccc(Cl)cc3)on2)cc1
InChIKey: UTPMJHPEJCVSJU-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha production using arachidonic acid as substrate by colorimetric method
Measurement: IC50 = 1340 nM (pChEMBL 5.869999885559082)
Descriptors: MW 475.96, ALogP 6, HBA 7, HBD 0, PSA 70.15, QED 0.22
Compound (SMILES): O=C(c1cccc2ccccc12)c1cn(CC2CCOCC2)c2ccc(O)cc12
InChIKey: USRUTFMMGDBKMJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55,940 from N-terminal HA-tagged human CB1 receptor expressed in HEK293 cell membranes after 1 hr by microbeta scintillation counting method
Measurement: Ki = 823.8 nM (pChEMBL 6.079999923706055)
Descriptors: MW 385.46, ALogP 5.16, HBA 4, HBD 1, PSA 51.46, QED 0.49
Compound (SMILES): FC1(F)CC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3nc(C(F)(F)F)cs3)n2)C1
InChIKey: FIHMFIIGBKKTHS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 497.38, ALogP 5.38, HBA 8, HBD 2, PSA 88.51, QED 0.46
Compound (SMILES): O=[N+]([O-])c1cc([N+](=O)[O-])c(-c2ccccc2COc2cccc(C(F)(F)F)c2)cc1F
InChIKey: PJMBAGIEJSKTII-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1 using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UPLC-MS/MS analysis
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 436.32, ALogP 5.91, HBA 5, HBD 0, PSA 95.51, QED 0.27
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CC4(C3)CC(F)(F)C4)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: RHCDZLRZYCRNDX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presence of NADPH and 30 uM NADP ny fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 490.43, ALogP 5.54, HBA 6, HBD 2, PSA 75.62, QED 0.54
Compound (SMILES): Cn1c(=O)n(CC(=O)c2ccncc2)c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc21
InChIKey: IMASPFRSKGCTIB-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 1743 nM (pChEMBL 5.760000228881836)
Descriptors: MW 428.47, ALogP 0.81, HBA 8, HBD 1, PSA 120.13, QED 0.58
Compound (SMILES): CN(C)c1ccnc(Nc2ncc3c(n2)-c2c(c(C(N)=O)nn2C)CC3)c1
InChIKey: BMCUQYKSQLZUHS-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 364.41, ALogP 1.28, HBA 8, HBD 2, PSA 114.85, QED 0.72
Compound (SMILES): Clc1ccc(-c2nc3ccc(-c4ncon4)cn3c2CN2CCn3ncnc3C2)c(Cl)c1
InChIKey: MFTNCMHUMNPULS-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P11168
Assay: Inhibition of human GluT2 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 467.32, ALogP 3.97, HBA 9, HBD 0, PSA 90.17, QED 0.4
Compound (SMILES): Cc1cc(C#Cc2cccnc2)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(N)(=O)=O)cc3)CC2)nc2ccsc12
InChIKey: XNNQDLOBHSMJCJ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 RES056 reverse transcriptase K103N/Y181C double mutant infected in human MT4 cells assessed as protection against virus-induced cytotoxicity by MTT assay
Measurement: EC50 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 624.79, ALogP 5.62, HBA 9, HBD 2, PSA 123.33, QED 0.22
Compound (SMILES): COc1cc(OC)c2c(=O)c(-c3ccc(OCc4ccc(C(F)(F)F)cc4)c(OC)c3)coc2c1
InChIKey: GVPUUCMDVZFUHY-UHFFFAOYSA-N
Target: Zinc finger protein GLI1 (SINGLE PROTEIN), Mus musculus
UniProt: P47806
Assay: Inhibition of Gli1 transcriptional activity in mouse embroyonic fibroblasts after 24 hrs by renilla luciferase reporter gene assay
Measurement: IC50 = 55290 nM (pChEMBL 4.260000228881836)
Descriptors: MW 486.44, ALogP 6.08, HBA 6, HBD 0, PSA 67.13, QED 0.32
Compound (SMILES): Nc1oc2cnccc2c1Nc1cccc(C2CC2)c1
InChIKey: PLUTUNGOEFOMKE-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 265.32, ALogP 4.03, HBA 4, HBD 2, PSA 64.08, QED 0.75
Compound (SMILES): O=C(O)c1ccnc(-n2nc(C3CC3)cc2O)c1
InChIKey: WEZPYYZPYXGXHK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 245.24, ALogP 1.55, HBA 5, HBD 2, PSA 88.24, QED 0.86
Compound (SMILES): CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](OC(=O)NCCCN)[C@@H](C(=O)O)C[C@H]1NC(=N)N.O=C(O)C(F)(F)F
InChIKey: INDGWLGCZCKEJP-UIDTYADTSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/WSN/1933(H1N1)) neuraminidase H275Y mutant pre-incubated for 10 mins before 4-MUNANA substrate addition by fluorometry
Measurement: IC50 = 34.3 nM (pChEMBL 7.460000038146973)
Descriptors: MW 428.53, ALogP -0.06, HBA 6, HBD 7, PSA 192.65, QED 0.14
Compound (SMILES): NC(=[Se])c1ccc(S(N)(=O)=O)cc1
InChIKey: CZIIHSLWIYNAMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 44.2 nM (pChEMBL 7.360000133514404)
Descriptors: MW 263.18
Compound (SMILES): CCNc1cnc2[nH]ccc2c1-c1nc2c(c(C(C)(C)S(C)(=O)=O)n1)OC[C@@H]1COC[C@@H](C)N21
InChIKey: PAEFRKXGUAROEW-KGLIPLIRSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT29 cells assessed as reduction in Chk1 phosphorylation at Ser345 residues after 4 hrs by Alexa Fluor 488 staining based fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 486.6, ALogP 2.72, HBA 9, HBD 2, PSA 122.33, QED 0.56
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(N)n2)n1)C1CC1
InChIKey: PRARPIBZHWEZPY-GHMZBOCLSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 339.45, ALogP 2.94, HBA 7, HBD 3, PSA 101.64, QED 0.71
Compound (SMILES): CCn1c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc2n(C)c1=O
InChIKey: NTXCSBXLYQAHFO-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 3970 nM (pChEMBL 5.400000095367432)
Descriptors: MW 337.4, ALogP 0.55, HBA 6, HBD 1, PSA 90.17, QED 0.88
Compound (SMILES): O=[N+]([O-])c1cc(S(=O)(=O)N2CCN(c3ccc(/C=C/c4cc(Cl)cc(Cn5ccnc5)c4)cc3)CC2)ccc1Cl
InChIKey: XZKURWCDHCLIRB-OWOJBTEDSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of recombinant CYP11B1 (unknown origin) expressed in human AD293 cells using 11-deoxycortisol as substrate pretreated for 60 mins followed by substrate addition and measured after 12 hrs by LC/MS analysis
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 598.51, ALogP 5.83, HBA 7, HBD 0, PSA 101.58, QED 0.14
Compound (SMILES): FC1(F)CC2(CC(Nc3nc(Nc4ccnc(C(F)(F)F)c4)nc(-c4cncc(C(F)(F)F)n4)n3)C2)C1
InChIKey: UQNYKCNMQIBEFQ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 532.4, ALogP 5.49, HBA 8, HBD 2, PSA 101.4, QED 0.42
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: NTKHRYLRDAXKRH-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presence of NADPH and 30 uM NADP ny fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 479.39, ALogP 5.31, HBA 7, HBD 2, PSA 99.41, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccc(Cl)cc3)n2-c2ccccc2)cc1
InChIKey: YXKRBFIZRCEMLB-FLFQWRMESA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by Lineweaver-Burk plot analysis
Measurement: Ki = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 441.97, ALogP 4.74, HBA 5, HBD 1, PSA 77.45, QED 0.5
Compound (SMILES): COc1cc2nccc(Nc3n[nH]c(C)c3C)c2cc1S(=O)(=O)C(C)(C)C
InChIKey: LHPFRDAGGDMRMZ-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of RIPK2 in human whole blood assessed as reduction in MDP-stimulated TNFalpha levels incubated for 30 mins followed by MDP addition measured after 5 hrs
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 388.49, ALogP 3.9, HBA 6, HBD 2, PSA 96.97, QED 0.7
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccccc3)n2-c2ccccc2)cc1
InChIKey: FXDROENCOYNWHS-LNVKXUELSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by Lineweaver-Burk plot analysis
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 407.52, ALogP 4.09, HBA 5, HBD 1, PSA 77.45, QED 0.55
Compound (SMILES): FC(F)c1cncc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: NNVCNVORYXXOAM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 475.44, ALogP 5.25, HBA 7, HBD 2, PSA 88.51, QED 0.55
Compound (SMILES): CCc1ccc([C@H](O)COc2ccc(CC3SC(=O)NC3=O)cc2)nc1
InChIKey: RMTFRGFLVHAYCI-TZHYSIJRSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Competitive displacement of fluorescently labelled PPAR tracer ligand from GST-tagged human PPARgamma ligand binding domain after 1 hr in dark by TR-FRET competitive binding assay
Measurement: IC50 = 3120 nM (pChEMBL 5.510000228881836)
Descriptors: MW 372.45, ALogP 2.65, HBA 6, HBD 2, PSA 88.52, QED 0.78
Compound (SMILES): COc1nc(N2C[C@H]3C(=O)N(C)C(=N)N[C@@]3(c3cc(-c4cccc(C#N)c4)cs3)C2)nc(C)c1F
InChIKey: CQZIPTUTHCRGDV-XDHUDOTRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 expressed in HEK293 cells
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 491.55, ALogP 2.86, HBA 8, HBD 2, PSA 118.23, QED 0.58
Compound (SMILES): CCOC(=O)c1nn(C)c2c1C(C)(C)Cc1cnc(Nc3ccccc3)nc1-2
InChIKey: OPUYYVDBFJRZHZ-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 377.45, ALogP 3.63, HBA 7, HBD 1, PSA 81.93, QED 0.7
Compound (SMILES): O=C(O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: GFBYPYUSXALYJS-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate incubated for 20 mins followed by substrate addition measured after 2 mins by Ellman's method
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 529.62, ALogP 5.17, HBA 8, HBD 3, PSA 126.33, QED 0.25
Compound (SMILES): COc1ccc(N(CCCCN2CCC(O)(c3ccc(Cl)c(C(F)(F)F)c3)CC2)c2ccc(OC)cc2)cc1
InChIKey: DYLSSJRMONSQGQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Displacement of [3H]5-CT from human 5-HT1D receptor expressed in HEK293T cells by radioligand binding assay
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 563.06, ALogP 7.28, HBA 5, HBD 1, PSA 45.17, QED 0.26
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1)C(=O)N(C)C
InChIKey: GFSAAPLIWHCOTJ-GHMZBOCLSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 423.44, ALogP 3.05, HBA 7, HBD 2, PSA 95.93, QED 0.71
Compound (SMILES): O=C1c2ccccc2C(=O)c2[nH]c(-c3cscn3)nc21
InChIKey: TYUCXCJOXMYOTN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 using D-Trp as substrate
Measurement: IC50 = 119.6 nM (pChEMBL 6.920000076293945)
Descriptors: MW 281.3, ALogP 2.31, HBA 5, HBD 1, PSA 75.71, QED 0.58
Compound (SMILES): FC(F)(F)Sc1ccc(NCc2ccccc2)cc1
InChIKey: NPAORROXZMAKEM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human recombinant PTP1B using pNPP as substrate by fluorescence spectrometric analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 283.32, ALogP 4.91, HBA 2, HBD 1, PSA 12.03, QED 0.8
Compound (SMILES): CC(C)Nc1nc(NC(C)C)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: WDSFOQJWJKBMPM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 90 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 340.35, ALogP 3.59, HBA 6, HBD 2, PSA 75.62, QED 0.87
Compound (SMILES): Cc1cc(Cn2c(=O)n(Cc3nnc(C)s3)c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc32)n(C)n1
InChIKey: NEBXSPXALDDNCB-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 515.62, ALogP 1.29, HBA 11, HBD 1, PSA 133.77, QED 0.39
Compound (SMILES): CCOC(=O)c1c(-c2ccc(Br)cc2F)[nH]c2c1cc(O)c1ccccc12
InChIKey: DKBKILFGOBVVSU-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-LO expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by RP-HPLC analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 428.26, ALogP 5.77, HBA 3, HBD 2, PSA 62.32, QED 0.41
Compound (SMILES): Fc1cc(F)c(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1F
InChIKey: MRBFFDHADFWESD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG-tagged JARID1B (2 to 751 residues) expressed in baculovirus infected Sf9 cells using H3K4me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 438.33, ALogP 4.41, HBA 5, HBD 1, PSA 72.28, QED 0.37