lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1CC[C@@H](NC(=O)c2cc3cc(-c4ccco4)cnc3n(Cc3cccc(F)c3)c2=O)CC1
InChIKey: KMZUTBHXIWDQQV-LMTLIKQPSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-WIN55212-2 from human CB2 receptor transfected in CHO cells membrane incubated for 90 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 459.52, ALogP 5.15, HBA 5, HBD 1, PSA 77.13, QED 0.45
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(Cc4ccccc4F)CC3)nc12
InChIKey: BQFAYRBTODBBSH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human recombinant BuChe using butyrylthiocholine iodide as substrate incubated for 10 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 412.53, ALogP 3.89, HBA 5, HBD 1, PSA 48.47, QED 0.67
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2cc(-c3cnc(C(C)C)[nH]3)oc12
InChIKey: QHFUFKACISHYKI-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of C-terminal His6-tagged BRD4 BD2 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay
Measurement: IC50 = 0.68 nM (pChEMBL 9.170000076293945)
Descriptors: MW 529.61, ALogP 7.09, HBA 6, HBD 2, PSA 93.28, QED 0.24
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccnc(OC)c4)c(C)c3c2)CC1
InChIKey: XQGPWLSDGMPBJU-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at ODN2006 stimulated human TRL9 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by ODN2006 stimulation measured after 22 hrs by SEAP reporter assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 378.52, ALogP 3.95, HBA 4, HBD 2, PSA 53.18, QED 0.68
Compound (SMILES): CCCn1c(=O)[nH]c(=O)c2c1nc(Cc1nc3cc4c(cc3[nH]1)OCO4)n2Cc1ccccc1
InChIKey: DXPLGNDECHMRIY-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 458.48, ALogP 2.54, HBA 8, HBD 2, PSA 119.82, QED 0.4
Compound (SMILES): Nc1ccc(S(=O)(=O)N2CCN(C(=O)c3cc(O)c(O)c(O)c3)CC2)cc1
InChIKey: OULPRIITYRITGZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase RNase H
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 393.42, ALogP 0.53, HBA 7, HBD 4, PSA 144.4, QED 0.44
Compound (SMILES): CCCc1nn(C2CCC(F)(F)CC2)c2ccc(C(=O)O)cc12
InChIKey: VZYUSEDTFNUHSK-UHFFFAOYSA-N
Target: Transcriptional enhancer factor TEF-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15562
Assay: Binding affinity to human TEAD2 (217 to 447 residues) expressed in Escherichia coli BL21 Star (DE3) by surface plasmon resonance assay
Measurement: Kd = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 322.36, ALogP 4.44, HBA 3, HBD 1, PSA 55.12, QED 0.91
Compound (SMILES): COc1ccc(-c2c(CN3CCOCC3)nc3scc(C(=O)NN)n23)cc1
InChIKey: ADWBIWIWVFJDMV-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human HER2 incubated for 40 to 45 mins and measured after 15 mins by Kinase-Glo Max assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 387.47, ALogP 1.51, HBA 8, HBD 2, PSA 94.12, QED 0.39
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3nc(Nc4cnn(C)c4)nc4ccn(C)c(=O)c34)CC2)CC1
InChIKey: YBTJPMATJNNXNI-SAABIXHNSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in IL1-stimulated human KARPAS-299 cells assessed as fluorescence intensity
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 495.59, ALogP 1.91, HBA 11, HBD 2, PSA 122.44, QED 0.55
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1cccc(OC)c1F
InChIKey: MLCDWARNPOODOL-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibitory Activity In Vitro Assay: KLK1 inhibitory activity in vitro was determined using standard published methods. Human KLK1 (Callbiochem) was incubated at 25° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 490.54, ALogP 3.37, HBA 7, HBD 1, PSA 87.38, QED 0.37
Compound (SMILES): CC(C)[C@H](NC(=O)CCN1CCC(Oc2ccccc2Cc2ccccc2)CC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](Cc1ccccc1)C(N)=O
InChIKey: OZHKISBSNKTCLM-SLNLPEDUSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of fluorophore-labeled mepyramine from Nluc-tagged human H1R expressed in HEK293T cells incubated for 2 hrs by NanoBRET competition binding assay
Measurement: Ki = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 835.01, ALogP 2.77, HBA 9, HBD 7, PSA 212.42, QED 0.07
Compound (SMILES): CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1
InChIKey: NPOKHPMWBDEANH-MFMYLMPHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human delta opioid receptor expressed in CHO cell membrane measured after 90 mins by liquid scintillation counting method
Measurement: Ki = 55.9 nM (pChEMBL 7.25)
Descriptors: MW 569.68, ALogP 1.63, HBA 6, HBD 6, PSA 162.65, QED 0.19
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C
InChIKey: HQXUWZBNZLHNRK-DMYQYOQPSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as stimulation intracellular calcium mobilization measured after 180 secs by Fluo-3-AM dye based fluorescence assay
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 3265.68
Compound (SMILES): C[Si](C)(C)c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: VQIGQFMEPHTOIB-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity against human LXRbeta expressed in human HEK293T cells co-expressing CMX-GAL4N-hLXRbeta incubated for 24 hrs by reporter gene assay
Measurement: EC50 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 316.32
Compound (SMILES): O=C(NC1C2CC3CC(C2)CC1C3)c1cn(CCCCCCS)c2ccccc12
InChIKey: MUWSMHYSNXQSGO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence plate reader assay
Measurement: IC50 = 19.03 nM (pChEMBL 7.71999979019165)
Descriptors: MW 410.63, ALogP 5.69, HBA 3, HBD 2, PSA 34.03, QED 0.43
Compound (SMILES): CN(C(=O)[C@]12ON=C(c3cccnc3)[C@H]1[C@@H]1CC[C@H]2C1)c1ccccc1
InChIKey: RCQNZFGCLVJEDP-HRWHDRTOSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in Chinese hamster V79 MZh cells using [14C]-deoxycorticosteron as substrate measured after 6 hrs by phosphoimager analysis
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 347.42, ALogP 3.26, HBA 4, HBD 0, PSA 54.79, QED 0.86
Compound (SMILES): O=c1c(O)c(-c2ccc(O)c(-c3c(O)cc(O)c4c(=O)cc(-c5ccc(OS(=O)(=O)O)cc5)oc34)c2)oc2cc(O)cc(O)c12
InChIKey: PYUUCJSZUWVXLT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin)
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 634.53, ALogP 4.32, HBA 13, HBD 7, PSA 245.4, QED 0.13
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(N4CCN(Cc5ccc(C(=O)NO)cc5)CC4)nc3)cc3c2cnn3C(C)C)c(=O)[nH]1
InChIKey: UKPCSPXPMAWCPG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 30 mins by multimode microplate reader analysis
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 648.77, ALogP 4.36, HBA 9, HBD 4, PSA 148.48, QED 0.14
Compound (SMILES): COc1cc(F)ccc1-c1ccnc2[nH]c(C3CCN(C(C)=O)CC3)cc12
InChIKey: RFAZOWNKGXUELJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA polymerase II phosphorylation at ser2 residue incubated for 6 hrs by fluorescence based assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 367.42, ALogP 4.1, HBA 3, HBD 1, PSA 58.22, QED 0.76
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3C=Cc3ccncc32)cc1
InChIKey: ZNRZSMMDQXGEGA-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant HDAC2 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 370.46, ALogP 4.16, HBA 4, HBD 2, PSA 57.26, QED 0.66
Compound (SMILES): CCCOc1ccc(-c2cc(OCCN3CCN(Cc4ccccc4)CC3)c3c(OC)cc(OC)cc3n2)cc1
InChIKey: VIWHUUDPXQKENJ-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 nsp13 ATPase-associated activity using ATP as substrate incubated for 30 mins by Biomol Green Reagent based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 541.69, ALogP 5.9, HBA 7, HBD 0, PSA 56.29, QED 0.22
Compound (SMILES): C[C@H]1CNC(=O)c2cnn3cc(cnc23)N[C@H](C)c2cc(F)cc(c2)O1
InChIKey: SBLCPBDVMUSESZ-WDEREUQCSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin)
Measurement: IC50 = 1.08 nM (pChEMBL 8.970000267028809)
Descriptors: MW 355.37, ALogP 2.55, HBA 6, HBD 2, PSA 80.55, QED 0.65
Compound (SMILES): O=C(COc1ccc2cc(Oc3ccc(C(F)(F)F)cn3)ccc2n1)N1CCNCC1
InChIKey: WTTVPKPPGWGFST-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG channel by electrophysiology
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 432.4, ALogP 3.25, HBA 6, HBD 1, PSA 76.58, QED 0.67
Compound (SMILES): O[C@H]1CCCC[C@@H]1N1CCN(CCCc2ccc(Br)cc2)CC1
InChIKey: FNJRTKRTEYIVLK-OALUTQOASA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma-2 receptor in Sprague-Dawley rat liver membrane incubated for 90 mins in presence of by liquid scintillation counter analysis (+)-pentazocine by liquid scintillation counter analysis
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 381.36, ALogP 3.3, HBA 3, HBD 1, PSA 26.71, QED 0.85
Compound (SMILES): NC(=O)c1cc2c(-c3cc(N)c(C(=O)NC4CC4)s3)cccc2s1
InChIKey: IIGCQCAUAFMZHK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human DYRK1B incubated for 130 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 813.6 nM (pChEMBL 6.090000152587891)
Descriptors: MW 357.46, ALogP 3.2, HBA 5, HBD 3, PSA 98.21, QED 0.67
Compound (SMILES): c1ccc(Cn2ccc3c(N4CCC5(COC5)C4)nc4ccccc4c32)cc1
InChIKey: FXLAYJYSKVUBHQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorometric analysis
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 369.47, ALogP 4.46, HBA 4, HBD 0, PSA 30.29, QED 0.53
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3P(C)(C)=O)n1)CN(C)CC2
InChIKey: QWCVGHXDHVKGAQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in human PBMC assessed as inhibition of SLP76 phosphorylation incubated for 1 hr by ELISA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 471.93, ALogP 4.86, HBA 7, HBD 2, PSA 79.38, QED 0.5
Compound (SMILES): CC(C)c1cnc(N2CC(CS(C)(=O)=O)C2)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: KBRHRZPPQDIMOA-RLWLMLJZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST tagged recombinant wild type human EGFR expressed in baculovirus infected Sf9 insect cells expression system using 5-FAM-EEPLYINSFPAKKK-CONH peptide as substrate preincubated for 10 mins followed by peptide substrate addition in presence of ATP
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 543.67, ALogP 3.07, HBA 10, HBD 2, PSA 124.44, QED 0.46
Compound (SMILES): N#Cc1ccc(CN2Cc3c(cc(Br)c(OCc4ccc(-c5ccccc5)cc4)c3Br)C[C@H]2C(=O)NS(=O)(=O)c2ccc(Cl)c([N+](=O)[O-])c2)cc1
InChIKey: QNYPSLHCWSPLIO-UMSFTDKQSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Binding affinity to Mcl-1 (unknown origin) assessed as inhibition constant using 5-FAM-QEDIIRNIARHLAQVGDSMDRSIPPG as substrate
Measurement: Ki = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 850.97, ALogP 8.32, HBA 8, HBD 1, PSA 142.64, QED 0.11
Compound (SMILES): Fc1ccccc1-c1nnn2c1COC1CN(Cc3ccccc3)CC12
InChIKey: BZGBCMQYDJZLBR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 350.4, ALogP 3.04, HBA 5, HBD 0, PSA 43.18, QED 0.73
Compound (SMILES): O=c1[nH]c(=O)n(C2CC2)c2nc(Cc3nc4ccccc4[nH]3)n(Cc3ccccc3)c12
InChIKey: GLUWCNQLKSIYKQ-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 412.45, ALogP 2.74, HBA 6, HBD 2, PSA 101.36, QED 0.46
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnn2C)c2c(n1)c(-c1ccn[nH]1)nn2C
InChIKey: AIRFZNQGDRBDOC-LLVKDONJSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of human recombinant ATR incubated for 40 mins by fluorescence based analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 379.43, ALogP 1.38, HBA 9, HBD 1, PSA 102.57, QED 0.57
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@]4(C)C(=O)c4cc(C)cc(C)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: AQELMVSXQAHBQJ-TURLPOKTSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from rat MOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 99.4 nM (pChEMBL 7)
Descriptors: MW 527.71, ALogP 5.81, HBA 5, HBD 0, PSA 48, QED 0.44
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)c2ccnc(Cl)c2)cc1Nc1nccc(-c2cn(CCCO)c3ccccc23)n1
InChIKey: XELFLRFPUQAHBD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) by mobility shift assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 629.17, ALogP 5.53, HBA 10, HBD 3, PSA 120.67, QED 0.14
Compound (SMILES): Cl.NOCc1ccccc1
InChIKey: HYDZPXNVHXJHBG-UHFFFAOYSA-N
Target: Alanine--glyoxylate aminotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21549
Assay: Inhibition of recombinant wild type His-tagged AGT (unknown origin) expressed in Escherichia coli BL21 assessed as inhibition constant using L-alanine and glyoxylate as a substrate in presence of PLP
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 123.15, ALogP 1.08, HBA 2, HBD 1, PSA 35.25, QED 0.6
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@]4(C)C(=O)c4ccc(-c6ccccc6)cc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: GXGBAGBZGRFOKT-ZBNRJEFASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from rat MOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 728 nM (pChEMBL 6.139999866485596)
Descriptors: MW 575.75, ALogP 6.86, HBA 5, HBD 0, PSA 48, QED 0.29
Compound (SMILES): Cn1c(-c2ccccc2)nc2cc(B(O)O)ccc21
InChIKey: GNWLWMNJEJNOHA-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 > 360 nM (pChEMBL 6.443999767303467)
Descriptors: MW 252.08
Compound (SMILES): C#CCN(C)Cc1cccc(NC(=O)CCCCCCC(=O)NO)c1
InChIKey: FQVRLKIMFQKGHF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 (379 to 382 residues) using RHKKAc as flurogenic substrate
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 345.44, ALogP 2.54, HBA 4, HBD 3, PSA 81.67, QED 0.25
Compound (SMILES): CNC(=O)N(c1ccc(S(=O)(=O)Nc2ccon2)cn1)c1cc(Cl)c(-c2cccc(OCC(F)(F)F)c2)cc1OC
InChIKey: HMPFLYJAQNHZHN-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 by PatchXpress assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 611.99, ALogP 5.62, HBA 8, HBD 2, PSA 135.89, QED 0.25
Compound (SMILES): CCOC(=O)C1=CN(C(=O)c2ccccc2)C=C(C(=O)OCC)C1c1ccsc1
InChIKey: BYAMRCBIAVXBKX-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Binding affinity to N-terminal his-tagged human SIRT5 (34 to 302 residues) expressed in Escherichia coli assessed as dissociation constant using NAD+ as substrate
Measurement: Kd = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 411.48, ALogP 3.88, HBA 6, HBD 0, PSA 72.91, QED 0.67
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](CCSSCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)O
InChIKey: GJIFCEKRNNRBMK-CEIPDFQMSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H]NT(8-13) from human NTSR1 F2.65C mutant expressed in HEK293 cell membranes by radioligand displacement assay
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 896.15, ALogP -1.42, HBA 13, HBD 14, PSA 370.08, QED 0.02
Compound (SMILES): CCn1c(=O)c2c(c3ccc(C)nc31)O[C@@](C)(CCO)C[C@H]2C=C(C)C
InChIKey: IOKJCBWLGAJZFW-VFNWGFHPSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5A1 (535 to 860 residues) (unknown origin) expressed in Escherichia coli BL21 using [3H-GMP] or [3H-AMP] as substrate incubated for 15 mins by liquid scintillation counting method
Measurement: IC50 = 4250 nM (pChEMBL 5.369999885559082)
Descriptors: MW 356.47, ALogP 3.7, HBA 5, HBD 1, PSA 64.35, QED 0.85
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2N(C)CC(=O)N3)[C@H]2C[C@H]21)c1ccc(Cl)cc1
InChIKey: VWPGAXIXIAUWJK-CEXWTWQISA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 484, ALogP 2.09, HBA 7, HBD 2, PSA 93.7, QED 0.65
Compound (SMILES): CN(C)CCCNC(=O)c1nc2c(N3CCc4ccccc43)ncnc2s1
InChIKey: CXNIDEGZWPEOCF-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of phosphorylation of eIF4E (unknown origin)
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 382.49, ALogP 2.46, HBA 7, HBD 1, PSA 74.25, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(CCN2CN(Cc3ccc(F)cc3F)CCS2(=O)=O)cc1
InChIKey: JDOJMVSSARNUMH-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 assessed as inhibition constant preincubated for 15 mins by measured for 10 to 100 secs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 85.5 nM (pChEMBL 7.070000171661377)
Descriptors: MW 445.51, ALogP 1.26, HBA 5, HBD 1, PSA 100.78, QED 0.72
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(N[C@@H]4CCCc5cc(C#N)ccc54)cc23)cc(C)n1
InChIKey: DFSMRMOJSDQSDN-HSZRJFAPSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of wild type pcDNA5FRT-TO-GFP fused - LRRK2 (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 393.49, ALogP 5.6, HBA 4, HBD 2, PSA 77.39, QED 0.47
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc(N(CCCO)Cc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: NKRKEQBTIYLTPA-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 494.56, ALogP 1, HBA 11, HBD 3, PSA 173.68, QED 0.38
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NC(=O)c4ccc5c(c4)OCCO5)CO3)c2n1
InChIKey: FGJQMRKSDIRTPZ-AXMJJZENSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus DNA topoisomerase 4 decatenation activity using kDNA as substrate incubated for 10 to 20 min by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 485.47, ALogP 1.62, HBA 9, HBD 2, PSA 121.26, QED 0.54
Compound (SMILES): Cc1nc(-c2cnc(N(C)C)[nH]c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: ABPUXKCLONETJM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 403.45, ALogP 2.79, HBA 8, HBD 1, PSA 101.82, QED 0.55
Compound (SMILES): CCCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: MHRLEHSQYIDFOB-TWMOVOSLSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged human LEAP2-SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: IC50 = 8.511 nM (pChEMBL 8.069999694824219)
Descriptors: MW 3358.98
Compound (SMILES): CC(NC1=NS(=O)(=O)c2cc(Br)ccc2N1)c1ccccc1
InChIKey: YKDBRWFQRGQWCT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 assessed as inhibition constant incubated for 1 hr prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 380.27, ALogP 3.27, HBA 4, HBD 2, PSA 70.56, QED 0.84
Compound (SMILES): C=C1CC[C@H]2[C@@](C)(CCC[C@]2(C)C(=O)O)[C@@H]1C/C=C(\C)[C@H]1CCc2c(O)c(CC3C(=O)C(C(C)=O)=C(O)C(C)(C)C3O)c(O)c(C(=O)CCC)c2O1
InChIKey: PUHUUEYLYYLTGI-ZNALYMAFSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease using MCA-AVLQSGFR-Lys(Dnp)-Lys-NH2 as flurogenic substrate pre-incubated with compound for 10 mins followed by substrate addition measured after 10 mins by FRET assay
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 720.9, ALogP 7.5, HBA 9, HBD 5, PSA 178.66, QED 0.09
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(C3CC3)c2C1=O
InChIKey: SMYKBETUHPQRLG-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 572 nM (pChEMBL 6.239999771118164)
Descriptors: MW 456.55, ALogP 3.5, HBA 6, HBD 2, PSA 105.62, QED 0.59
Compound (SMILES): CCc1cnn2c(NCc3ccc[n+]([O-])c3)cc(C3CCCC[C@H]3CCO)nc12
InChIKey: KCKWQKDFLCMFNR-OYKVQYDMSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of recombinant CDK5 (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotinylated-histone H1 as substrate incubated for 1 hr in presence of 33P-ATP by liquid scintillation counter method
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 395.51, ALogP 3.19, HBA 6, HBD 2, PSA 89.39, QED 0.47
Compound (SMILES): O=C(O)c1cc(O)c(=O)c2c(O)c(O)cc(-c3ccccc3)c2c1
InChIKey: APVKIUGNQLIXRE-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of human KDM4C measured by AlphaLISA assay
Measurement: IC50 = 24370 nM (pChEMBL 4.610000133514404)
Descriptors: MW 324.29, ALogP 2.68, HBA 5, HBD 4, PSA 115.06, QED 0.54
Compound (SMILES): COc1ccc(/C=C/c2cc(OC)cc(OCc3ccc(OC(C)C(=O)O)c(F)c3)c2)cc1
InChIKey: AOYSVQRIFFGPEM-SNAWJCMRSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human PPARdelta measured by dual luciferase reporter gene assay
Measurement: EC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 452.48, ALogP 5.44, HBA 5, HBD 1, PSA 74.22, QED 0.41
Compound (SMILES): c1ccc(-c2nnc(Cc3c[nH]c4ccccc34)nc2-c2ccccc2)cc1
InChIKey: ZRUREFLANVLNAL-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Antagonist activity at human GPR84 expressed in HTLA cells co-expressing GPR84-tango plasmid assessed as beta-arrestin recruitment at 10 uM preincubated for 30 mins followed by ZQ-16 addition and measured after 36 to 40 hrs by PRESTO-Tango assay
Measurement: IC50 = 27.54 nM (pChEMBL 7.559999942779541)
Descriptors: MW 362.44, ALogP 5.28, HBA 3, HBD 1, PSA 54.46, QED 0.47
Compound (SMILES): C[C@@H]1CN(c2ccc(-c3n[nH]c4cnc(N5[C@H](C)CCC[C@@H]5C)nc34)cn2)CCN1
InChIKey: RJCVCOCSWGHLMV-OAGGEKHMSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (1 mM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 1 mM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 406.54, ALogP 2.98, HBA 7, HBD 2, PSA 85.86, QED 0.69
Compound (SMILES): O=C1NC(c2cccc(NCCC3CC3)n2)(c2cccc(Nc3ccc(F)c(F)c3)n2)CC(O)=C1Sc1ccccc1Cl
InChIKey: XJPQZHPKRRVQMS-UHFFFAOYSA-N
Target: L-lactate dehydrogenase B chain (SINGLE PROTEIN), Homo sapiens
UniProt: P07195
Assay: Inhibition of LDHB (unknown origin)
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 620.12, ALogP 7.69, HBA 7, HBD 4, PSA 99.17, QED 0.14
Compound (SMILES): CNS(=O)(=O)c1cc(-c2ccn3nc(N)c(C(=O)N[C@@H](CO)C4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C(F)(F)F)C2
InChIKey: DEYMNPBPRBGNRS-ZBEGNZNMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 581.58, ALogP 1.29, HBA 9, HBD 4, PSA 172.02, QED 0.31
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCN1CCN(c2ccccc2)CC1
InChIKey: DEBVZIFHEKEUKP-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 335.45, ALogP 2.79, HBA 3, HBD 0, PSA 26.79, QED 0.86
Compound (SMILES): COc1ccc(C2=NN(c3ccccn3)C(=O)C2)cc1
InChIKey: DXWBEIPEDHYRHM-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PD-L1 interaction in CHO-K1 cells transfected with PD-1-YFP/SHP-2-CFP and measured by FRET assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 267.29, ALogP 2.23, HBA 4, HBD 0, PSA 54.79, QED 0.86
Compound (SMILES): Nc1nc(NCCNc2cccc(Cl)c2Cl)nc(NCCc2c[nH]c3ccccc23)n1
InChIKey: VZXAKUVFURTEQJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK293 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 475 nM (pChEMBL 6.320000171661377)
Descriptors: MW 457.37, ALogP 4.42, HBA 7, HBD 5, PSA 116.57, QED 0.24
Compound (SMILES): COc1ccc([C@@H](O)[C@]2(C)C[C@@]34CC[C@]2(OC)[C@@H]2Oc5c(OC)ccc6c5[C@@]23CCN(CC2CC2)[C@@H]4C6)cc1
InChIKey: PRUMTDZQWZNRBJ-GLYUIJDASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat DOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 178.3 nM (pChEMBL 6.75)
Descriptors: MW 531.69, ALogP 5.05, HBA 6, HBD 1, PSA 60.39, QED 0.54
Compound (SMILES): NC(=O)[C@@H]1CC(=O)NCCCC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1
InChIKey: OKFCZQOQWOKJMP-QDRJTDBGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOP expressed in CHO-K1 cell membrane incubated for 60 mins by Microscint-counting analysis
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 738.85, ALogP 0.34, HBA 8, HBD 9, PSA 250.63, QED 0.12
Compound (SMILES): Nc1ncc2c(n1)-c1c([nH]c3ccc(-c4ccc(F)cc4)cc13)CCC2
InChIKey: PJFCVWLQATZEIU-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 3-phosphate 5-kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2I7
Assay: Inhibition of PIKFYVE in HEK293 cells by NanoBRET assay
Measurement: IC50 = 11.48 nM (pChEMBL 7.940000057220459)
Descriptors: MW 344.39, ALogP 4.5, HBA 3, HBD 2, PSA 67.59, QED 0.53
Compound (SMILES): CC(=O)N1C2CC1CN(C1CCN(c3ccc(Nc4nccc(-c5ccc(C(=O)NCC#N)cc5)n4)cc3)CC1)C2
InChIKey: HJOQGTDSHRNBPK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Assay: NCEs were screened using in vitro JAK (1, 2 and 3) kinase assay on ADP Glo platform (Promega). Fixed amount of recombinant purified human JAK (25 ng of JAK1 and 10 ng of JAK2 and JAK3 per reaction, from Life Technologies Ltd) were incubated with increasing concentration of NCEs in 1× kinase reaction buffer (40 mM Tris-Cl, pH7.5, 20 mM MgCl2, 0.1 mg/ml BSA and 50 μM DTT). Enzymatic reaction was initiated by adding a substrate cocktail containing 50 μM of ATP (final concentration) and 5 μg for JAK1 and 2.5 μg for JAK2 and JAK3 of polyGln4Tyr1 (Signal Chem) in total 25 μl of reaction in 96 well plate. The reaction was incubated at room temperature for 1 hr.After 1 hr of incubation equal volume (25 μl per reaction) of ADP Glo was added and incubated at room temperature for 40 min.This was followed by addition of kinase detection reagent (50 μl per reaction) and incubation at room temperature for 30 min. Finally, plate was read for luminescence at an integration time of 500 millisecond per well.
Measurement: IC50 = 50.7 nM (pChEMBL 7.289999961853027)
Descriptors: MW 550.67, ALogP 3.41, HBA 8, HBD 2, PSA 117.49, QED 0.43
Compound (SMILES): COC1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CCC(c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-SIYOEGHHSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant RET M918T (unknown origin) incubated for 120 mins by Perkin Elmer electrophoretic mobility shift platform method
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: RBMBLJOYIGVBNO-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/cyclin-D3 (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 433.49, ALogP 2.46, HBA 7, HBD 2, PSA 86.28, QED 0.65
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: RUHYGYHBVKWREW-CMOCDZPBSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 MPro using Dabcyl-KTSAVLQSGFRKME-Edans as substrate preincubated for 30 mins followed by substrate addition measured after 15 mins by FRET assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 502.61, ALogP 1.68, HBA 6, HBD 4, PSA 142.7, QED 0.3
Compound (SMILES): Fc1cc(COC2CCN(Cc3cc4ccc(Cl)cc4[nH]3)CC2)ccc1Cl
InChIKey: UEXJPFHGKCBUSS-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 407.32, ALogP 5.8, HBA 2, HBD 1, PSA 28.26, QED 0.58
Compound (SMILES): CCN(CC)C(=O)c1coc2c1C(=O)C(=O)c1c-2ccc2c1C=CC(=O)C2(C)C
InChIKey: JGZOYQYOLGUNDA-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 by absorbance based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 391.42, ALogP 3.68, HBA 5, HBD 0, PSA 84.66, QED 0.75
Compound (SMILES): COc1cc(CCNC2=NC(C#Cc3ccc(Cl)s3)=NC3=NC=NC32)ccc1O
InChIKey: MPFMHAAXLGXWPP-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity towards human adenosine A3 receptor
Measurement: Ki = 6820 nM (pChEMBL 5.170000076293945)
Descriptors: MW 425.9, ALogP 2.92, HBA 8, HBD 2, PSA 90.93, QED 0.74
Compound (SMILES): CCCCNc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: LDLJTALPLRVDBD-IDTAVKCVSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Agonist activity at human P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 30199.52 nM (pChEMBL 4.519999980926514)
Descriptors: MW 563.29, ALogP 0, HBA 14, HBD 7, PSA 265.14, QED 0.13
Compound (SMILES): COc1cc2nc(N3CCN(CCCCCC(=O)NO)CC3)nc(NC3CCN(C(C)C)CC3)c2cc1OC
InChIKey: PZHMEFBKSLGDIS-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of GLP (unknown origin)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 543.71, ALogP 3.12, HBA 10, HBD 3, PSA 115.32, QED 0.21
Compound (SMILES): CN(Cc1ccc(C(=O)NO)cc1[18F])CC12CC3CC(CC(C3)C1)C2
InChIKey: IGZQZELTOHAHNW-GJQNQZCXSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using fluorogenic substrate
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 346.45, ALogP 3.59, HBA 3, HBD 2, PSA 52.57, QED 0.63
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)c1cc(Cl)ccc1Cl)B(O)O.O=C(O)CC(O)(CC(=O)O)C(=O)O
InChIKey: HMTYOOYHLZDMOH-YDALLXLXSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 361.03
Compound (SMILES): CC(C)[C@H]1CO[C@]23CCN(Cc4ccc(Cl)cc4)C[C@H]2CCC(=O)N13
InChIKey: ODUYWULJYRWPSN-YVWKXTFCSA-N
Target: Type II NADH:quinone oxidoreductase NdhA (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P95200
Assay: Inhibition of Mycobacterium smegmatis MC2 155 recombinant ndhA assessed as rate of NADH oxidation in the presence of an electron acceptor menadione
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 362.9, ALogP 3.54, HBA 3, HBD 0, PSA 32.78, QED 0.82
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4c(F)cccc4C(F)(F)F)s3)cc2)CC1
InChIKey: QVZIQCVGMKXLJK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 479.5, ALogP 4.61, HBA 7, HBD 2, PSA 74.49, QED 0.41
Compound (SMILES): CCCNNC(=O)c1cnc(NCc2ccccc2)nc1
InChIKey: ZNFWUEMVXRQJAR-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 43.2 nM (pChEMBL 7.369999885559082)
Descriptors: MW 285.35, ALogP 1.73, HBA 5, HBD 3, PSA 78.94, QED 0.53
Compound (SMILES): Cl.NS(=O)(=O)c1ccc(OCCNCC2COc3ccccc3O2)cc1
InChIKey: DSIDRCLLZRECGD-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4 assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 290.8 nM (pChEMBL 6.539999961853027)
Descriptors: MW 364.42, ALogP 1.14, HBA 6, HBD 2, PSA 99.88, QED 0.71
Compound (SMILES): O=S(=O)(c1ccc2c(c1)CCO2)N1CCC(CCc2nccs2)CC1
InChIKey: KELHHTCITLAVHH-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by by Fluo-4AM staining based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.52, ALogP 3.11, HBA 5, HBD 0, PSA 59.5, QED 0.8
Compound (SMILES): COc1cc2nc(NCCCCCC(=O)NO)nc(NC3CCN(C(C)C)CC3)c2cc1OC
InChIKey: YAXJFGYPFUEOCZ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of GLP (unknown origin)
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 474.61, ALogP 3.41, HBA 9, HBD 4, PSA 120.87, QED 0.21
Compound (SMILES): CCCCNc1ncc(C(=O)NC2CCN(CCF)CC2)c(N[C@H]2CC[C@H](O)CC2)n1
InChIKey: OASIGFOZMTYWOR-SAABIXHNSA-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 incubated for 180 mins in presence of ATP by microfluidic capillary electrophoresis analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 436.58, ALogP 2.57, HBA 7, HBD 4, PSA 102.41, QED 0.42
Compound (SMILES): COc1ccc(/C=C/C(=O)Nc2cc[n+](Cc3cccc(F)c3)cc2)cc1OC.[Br-]
InChIKey: JYOKZRSSHWDBAN-BXTVWIJMSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE preincubated for 6 mins followed by substrate addition using butyrylthiocholine iodide as substrate by DTNB reagent based Ellman method
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 393.44, ALogP 3.83, HBA 3, HBD 1, PSA 51.44, QED 0.49
Compound (SMILES): CS(=O)(=O)c1cccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: HRNJHPQOHAYYJI-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 474.59, ALogP 3.7, HBA 6, HBD 2, PSA 109.32, QED 0.34
Compound (SMILES): CCCc1cc(C(=O)NC(C)(C)C)cc(C#Cc2ccc3c4c(oc3c2)C(C)(C)c2cc(NS(C)(=O)=O)ccc2C4=O)n1
InChIKey: SGCBBVKTBTZXBX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 597.74, ALogP 5.95, HBA 6, HBD 2, PSA 118.37, QED 0.27