lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)c1ccc(-c2cc3ncnc(SCC(=O)O)c3s2)cc1
InChIKey: GZXYMRLGHGNYBT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17B (SINGLE PROTEIN), Homo sapiens
UniProt: O94768
Assay: Binding affinity to C-terminal nano-luciferase tagged STK17B (unknown origin) expressed in HEK293 cells incubated for 2 hrs by nano-BRET assay based cellular target engagement assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 344.42, ALogP 3.74, HBA 6, HBD 1, PSA 80.15, QED 0.43
Compound (SMILES): Cc1cc(-c2ccnc(Nc3cnn(C)c3)n2)ccc1CNC(=O)C1CCC(C(C)(C)C)C1
InChIKey: TXWLSLXBFLASOB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as reduction in BTK phosphorylation measured after 30 mins by phosphotyrosine detection method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 446.6, ALogP 5.01, HBA 6, HBD 2, PSA 84.73, QED 0.56
Compound (SMILES): COC[C@]12C[C@H]1[C@@](CF)(c1cc(NC(=O)c3ccc(Cl)cn3)ccc1F)N=C(N)S2
InChIKey: BNGBJDRMXVMOAE-NSISKUIASA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of recombinant human BACE2 using fluorescence substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 452.91, ALogP 3.76, HBA 6, HBD 2, PSA 89.6, QED 0.7
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)[C@H]1CCCc2ccccc21
InChIKey: CAVJGRPSJPRJNJ-AWEZNQCLSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human coagulation factor alpha-thrombin using Boc-Val-Pro-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 = 421 nM (pChEMBL 6.380000114440918)
Descriptors: MW 319.37, ALogP 2.68, HBA 6, HBD 1, PSA 86.69, QED 0.78
Compound (SMILES): Cc1ccc(OC(F)F)c(-c2n[nH]cc2NC(=O)c2cnn3cccnc23)c1
InChIKey: UBCQNOFMXUGGQZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (812 to 1132 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay
Measurement: Ki = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 384.35, ALogP 3.28, HBA 6, HBD 2, PSA 97.2, QED 0.55
Compound (SMILES): O=c1c2c(Cl)cccc2nc([C@@H]2CC3(CC3)CN2c2ncnc3[nH]cnc23)n1-c1ccccc1
InChIKey: JMCOBLCEJSXBNG-SFHVURJKSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full-length recombinant N-terminal His-tagged PI3K p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 469.94, ALogP 4.44, HBA 7, HBD 1, PSA 92.59, QED 0.42
Compound (SMILES): COc1ccc(-c2noc(CC(=O)Nc3ccc(-c4ccc(NC(=O)Cc5onc(-c6ccc(OC)cc6)c5-c5ccc(OC)cc5)cc4)cc3)c2-c2ccc(OC)cc2)cc1
InChIKey: HULKLAUGAALDIZ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 assessed as peroxidase activity using arachidonic acid as substrate by colorimetric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 826.91, ALogP 10.39, HBA 10, HBD 2, PSA 147.18, QED 0.1
Compound (SMILES): Brc1ccc(C2Nc3ccc4ccccc4c3C3C=CCC32)cc1
InChIKey: YWQSTBRRGMJSAA-UHFFFAOYSA-N
Target: Prostate-specific antigen (SINGLE PROTEIN), Homo sapiens
UniProt: P07288
Assay: Inhibition of prostate specific antigen in human LNCaP cells
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 376.3, ALogP 6.43, HBA 1, HBD 1, PSA 12.03, QED 0.48
Compound (SMILES): CC1CCCC(C)N1C(=O)CCN1CCCc2ccccc21
InChIKey: ZJKKWZMKWAJTKP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from muscarinic M3 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 54954.09 nM (pChEMBL 4.260000228881836)
Descriptors: MW 300.45, ALogP 3.62, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): O=c1cc(CN2CCN(Cc3ccccc3)CC2)c2ccc(OCc3cccc(Br)c3)cc2o1
InChIKey: NCBPILFLMOPZQB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 pre-incubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 519.44, ALogP 5.45, HBA 5, HBD 0, PSA 45.92, QED 0.3
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: VJFNAJWMIIUIKO-YQSLKQGWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H][Ile5,6]deltorphin II from delta opioid receptor in rat brain membranes incubated for 45 mins by liquid scintillation counting method
Measurement: Ki = 2.25 nM (pChEMBL 8.649999618530273)
Descriptors: MW 431.49, ALogP 0.12, HBA 7, HBD 4, PSA 134.35, QED 0.5
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)N2CCCc3cc(Cl)ccc32)CC1
InChIKey: IMMDJFFGIHKYFC-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1a receptor expressed in human 1321N1 cells assessed as decrease in Arg8-vasopressin-stimulated calcium flux by fluorometric calcium assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 369.9, ALogP 4.34, HBA 2, HBD 0, PSA 26.79, QED 0.75
Compound (SMILES): CCOc1cccc(CN2[C@H]3CCn4c(nc5cc(C(=O)O)ccc54)[C@H]3[C@H](c3cccc(Cl)c3F)[C@]23C(=O)Nc2cc(Cl)ccc23)c1
InChIKey: NTPHWEOQINJKPH-GHFJTSGJSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: AlphaScreen Assay: 15 μL of compound in 20% DMSO (serial pre-dilutions of compound are done in 100% DMSO) is pipetted to the wells of a white OptiPlate-96 (Perkin Elmer). A mix consisting of 20 nM GST-MDM2 protein (aa 23-117) and 20 nM biotinylated p53 wt peptide (encompassing aa 16-27 of wt human p53, amino acid sequence QETFSDLWKLLP-Ttds-Lys-Biotin, molecular weight 2132.56 g/mol) is prepared in assay buffer (50 mM Tris/HCl pH 7.2; 120 mM NaCl; 0.1% bovine serum albumin (BSA); 5 mM dithiothreitol (DTT); 1 mM ethylenediaminetetraacetic acid (EDTA); 0.01% Tween 20). 30 μL of the mix is added to the compound dilutions and incubated for 15 min at rt while gently shaking the plate at 300 rounds per minute (rpm). Subsequently, 15 μL of premixed AlphaLISA Glutathione Acceptor Beads and AlphaScreen Streptavidin Donor Beads from PerkinElmer (in assay buffer at a concentration of 10 μg/mL each) are added and the samples are incubated for 30 min at rt in the dark (shaking 300 rpm). Afterwards, the signal is measured in a PerkinElmer Envision HIS Multilabel Reader using the AlphaScreen protocol from Perkin Elmer.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 671.56, ALogP 7.58, HBA 6, HBD 2, PSA 96.69, QED 0.19
Compound (SMILES): COc1cncc(C(=O)Nc2c[nH]nc2C(=O)Nc2ccc(CN(C)C)cc2)c1
InChIKey: IUBMYOISONSWIP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 394.44, ALogP 2.38, HBA 6, HBD 3, PSA 112.24, QED 0.57
Compound (SMILES): FC(F)(F)c1cccc(-c2cnc3c4cccnc4nn3c2)c1
InChIKey: IKLWYGIHNWBZDN-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI-TN-5B1-4 insect cells using p-tyramine as substrate preincubated for 15 mins followed by substrate addition and measured over 20 mins by horse-radish peroxidase/Amplex Red coupled fluorimetric analysis
Measurement: IC50 = 1020 nM (pChEMBL 5.989999771118164)
Descriptors: MW 314.27, ALogP 3.96, HBA 4, HBD 0, PSA 43.08, QED 0.53
Compound (SMILES): NC(=O)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: GNHYLWRHHLTWJO-IMFGXOCKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 541.46, ALogP 5.24, HBA 3, HBD 1, PSA 77.23, QED 0.42
Compound (SMILES): CCC[C@@H](C)COc1ccc([C@H](Cc2nnc(N)o2)NC(=O)[C@@H](C)c2ccccc2)cc1.Cl
InChIKey: RATKNEAWOCXBQD-VGTMEJJFSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP production by TR-FRET assay
Measurement: EC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 436.56, ALogP 4.67, HBA 6, HBD 2, PSA 103.27, QED 0.45
Compound (SMILES): CN1CCN(Cc2ccc(NC(=O)c3n[nH]c4ccc(-c5cccnc5)cc34)cn2)CC1
InChIKey: ONKHKERFMSOGOO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 427.51, ALogP 3.02, HBA 6, HBD 2, PSA 90.04, QED 0.51
Compound (SMILES): Cc1noc(C)c1-c1ccc2nc(-c3cnn(CC(C)(C)O)c3)nc(N3CCN(S(C)(=O)=O)C[C@@H]3c3ccccc3)c2c1
InChIKey: VHAGEDLCCPAUJD-HHHXNRCGSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of human full-length recombinant N-terminal His-tagged BRD4 (2 to 1362 residues) expressed in Sf9 cells using histone H4 peptide containing acetylated lysine residues as substrate preincubated with enzyme for 30 mins followed by incubation with substrate for 30 mins by Alphascreen assay based TR-FRET analysis
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 601.73, ALogP 4.36, HBA 10, HBD 1, PSA 130.48, QED 0.29
Compound (SMILES): CCCC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccncc6)cncc5[nH]4)c3n2)c1
InChIKey: SVVIVDKAJUKQCG-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 475.52, ALogP 4.76, HBA 7, HBD 3, PSA 138.02, QED 0.32
Compound (SMILES): O=C(Nc1cc2oc(N3CCOCC3)nc2cc1N1CCCCC1)c1cccc(-c2cn[nH]c2)n1
InChIKey: DBMFXHNNDCFLTG-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human THP-1 cells assessed as inhibition of LTA-induced TNF-alpha production preincubated for 60 mins followed by LTA stimulation and measured after 5 hrs by ELISA
Measurement: IC50 = 58.5 nM (pChEMBL 7.230000019073486)
Descriptors: MW 473.54, ALogP 3.69, HBA 8, HBD 2, PSA 112.41, QED 0.45
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)c1cncs1)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: CVDCDYPZZIBFOG-SFHVURJKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 453.54, ALogP 4.94, HBA 6, HBD 2, PSA 111.53, QED 0.4
Compound (SMILES): CCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1C[C@H](O)C(C)=C[C@@H]21
InChIKey: JXXVDKGGZIPBOC-KFWWJZLASA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB1R expressed in HEK293 cell membranes after 90 mins
Measurement: Ki = 25.6 nM (pChEMBL 7.590000152587891)
Descriptors: MW 302.41, ALogP 3.93, HBA 3, HBD 2, PSA 49.69, QED 0.81
Compound (SMILES): C[C@@H]1CN(c2ccc(C#N)c3ncccc23)C[C@@H]2CN(c3cccc4c3CCNC4)CCN21
InChIKey: TWCOLPRDAQZXDZ-KNQAVFIVSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Inhibition of human TLR8 expressed in HEK-Blue cells assessed as inhibition of R848-induced NF-kappaB and AP-1 activation measured after 20 hrs by quanti-blue based SEAP reporter gene assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 438.58, ALogP 3.15, HBA 6, HBD 1, PSA 58.43, QED 0.66
Compound (SMILES): CC[C@@H](C)[C@H](NC(=O)[C@@H]1C/C=C\C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: BWLOXFXBNUSZKM-QFIJLSENSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]Tyr3-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter analysis
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 830.04, ALogP -0.04, HBA 11, HBD 11, PSA 310.19, QED 0.06
Compound (SMILES): Cc1cc2ccnc(N[C@@H]3CCNC[C@H]3C(=O)NC3CCCC3)c2[nH]c1=O
InChIKey: KAJVIXPYLAGRLE-HZPDHXFCSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 369.47, ALogP 1.68, HBA 5, HBD 4, PSA 98.91, QED 0.66
Compound (SMILES): FC(F)(F)c1cc(-c2nnco2)ccc1Cl
InChIKey: WASVOWHKQQFANQ-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Biochemical Notum Enzymatic Activity Assay: An Echo liquid handler was used to acoustically dispense 500 nL of compounds into dry Greiner 384-well plates (catalog #781076), followed by 25 μL of 2 μM trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS, Sigma #74875) solution in 50 mM Tris, 5 mM CaCl2), 0.5 mM MgCl2, pH 7.4 assay buffer, and 25 μL of 2.38 nM notum carboxyesterase enzyme solution in the same buffer to every well in the assay plate. After 1 hour incubation at room temperature, fluorescence was measured on a PheraSTAR FSX microplate reader with an excitation wavelength of 485 nm and emission wavelength of 520 nm.
Measurement: IC50 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 248.59, ALogP 3.41, HBA 3, HBD 0, PSA 38.92, QED 0.78
Compound (SMILES): Cc1ccccc1CN1C2CCC1CC(NC(=O)c1ccc3ccccc3c1)C2
InChIKey: WAPWCWXQGLXTRS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Displacement of [3H]-8-OH-DPAT from rat cerebral cortex 5HT1A receptor measured after 15 mins by liquid scintillation counter method
Measurement: Ki = 192.7 nM (pChEMBL 6.710000038146973)
Descriptors: MW 384.52, ALogP 5.07, HBA 2, HBD 1, PSA 32.34, QED 0.68
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H](C#N)NC(=O)[C@H](Cc1cccc(Cl)c1)NC(=O)c1ccc(-c2cncnc2)cc1
InChIKey: VUELCPPLRJAJCW-SPTGULJVSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of recombinant human cathepsin K using Z-Leu-Arg-AMC as substrate measured after 20 mins
Measurement: Ki = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 554.05, ALogP 4.75, HBA 6, HBD 2, PSA 117, QED 0.28
Compound (SMILES): CCOP(=O)(OCC)C(Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)P(=O)(OCC)OCC
InChIKey: UDBUKRGXKGQDQR-UHFFFAOYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Induction of HMGCR degradation in human HepG2 cells incubated for 3 hrs by densitometric analysis
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 506.56, ALogP 7.39, HBA 7, HBD 1, PSA 91.29, QED 0.3
Compound (SMILES): Cc1cc(Nc2ccnnc2)c(=O)n2c1C(=O)NC21CCCCC1
InChIKey: TXTJPVXASVJOMW-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of recombinant human N-terminal DYKDDDDK-tagged MNK1(1 to 424 residues) expressed in baculovirus expression system using TATKSGSTTKNR as substrate preincubated for 10 mins followed by ATP addition and measured after 40 mins by luminescence based assay
Measurement: IC50 = 159.8 nM (pChEMBL 6.800000190734863)
Descriptors: MW 325.37, ALogP 2.05, HBA 6, HBD 2, PSA 88.91, QED 0.88
Compound (SMILES): NC(=O)c1cc(Cl)c2ccc(-c3ccc(CN4CCN(C5CC5)CC4)cc3)nn12
InChIKey: MZCKCDMDQWJOCV-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of PARP-2 (unknown origin)
Measurement: IC50 = 997.49 nM (pChEMBL 6)
Descriptors: MW 409.92, ALogP 3.03, HBA 5, HBD 1, PSA 66.87, QED 0.7
Compound (SMILES): O=C(/C=C/c1ccc(Cl)cc1)Nc1ccc2oc(=O)ccc2c1
InChIKey: SQCPGWSIAPLGCL-YCRREMRBSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 325.75, ALogP 4.1, HBA 3, HBD 1, PSA 59.31, QED 0.58
Compound (SMILES): CNC(=O)c1cn(C[C@H](F)CCc2ccc(NC(=O)Cc3cc(C(F)(F)F)ccn3)nn2)nn1
InChIKey: IYSACTQVCXVSMV-CYBMUJFWSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Enzymatic Activity Assay: The inhibition of purified recombinant human GAC by varying concentrations of inhibitors is assessed via a dual-coupled enzymatic assay. The glutamate produced by the glutaminase reaction is used by glutamate oxidase to produce α-ketoglutarate, ammonia, and hydrogen peroxide, with this hydrogen peroxide subsequently being used by horseradish peroxidase to produce resorufin in the presence of Amplex UltraRed. The assay buffer consisted of 50 mM Hepes (pH 7.4), 0.25 mM EDTA and 0.1 mM Triton X-100. GAC was incubated with potassium phosphate (10 minutes at room temperature) prior to incubation with inhibitor (10 minutes at room temperature). The final reaction conditions were as follows: 2 nM GAC, 50 mM potassium phosphate, 100 mU/mL glutamate oxidase (Sigma), 1 mM glutamine (Sigma), 100 mU/mL horseradish peroxidase (Sigma), 75 μM Amplex UltraRed (Life Technologies), and 1% (v/v) DMSO. The production of resorufin was monitored on a Perkin Elmer Envision plate reader (excitation 530 nm, emission 590 nm) either in a kinetics or endpoint mode (at 20 minutes). IC50 values were calculated using a four-parameter logistic curve fit.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 480.43, ALogP 1.99, HBA 8, HBD 2, PSA 127.58, QED 0.45
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2F)CC1
InChIKey: FRPYDYUBDGOHLI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]methylspiperone from human D2 receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 426.87, ALogP 4.23, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C/C=C/C(=O)O)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SNRUIWMOAHSUGQ-SNAWJCMRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Mus musculus
UniProt: Q62120
Assay: Inhibition of JAK2 V617F mutant in mouse BaF3 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 432.53, ALogP 3.97, HBA 7, HBD 2, PSA 96.17, QED 0.55
Compound (SMILES): O=C(NCCCN1CCCC1)c1cccc(-c2ccccc2N2CCN(CCc3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: LUFJXLBJGLJMFZ-UHFFFAOYSA-N
Target: N-lysine methyltransferase SMYD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRG4
Assay: Inhibition of SMYD2 (unknown origin) expressed in in human U2OS cells assessed as reduction in monomethylated p53 levels incubated for 24 hrs by immunofluorescence assay
Measurement: EC50 = 3230 nM (pChEMBL 5.489999771118164)
Descriptors: MW 565.59, ALogP 6.24, HBA 4, HBD 1, PSA 38.82, QED 0.3
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCc1cn(CCNc2c3c(nc4ccccc24)CCCC3)nn1
InChIKey: ALRPJVIDEJKLDX-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 1 min followed by substrate addition and measured after 10 mins by Ellman's method
Measurement: IC50 = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 651.8, ALogP 5.06, HBA 11, HBD 3, PSA 148.84, QED 0.15
Compound (SMILES): O=C(NCC1CC1)c1cc(N2CC[C@H](O)C2)nc(N2CCC[C@H](c3ccccc3)C2)n1
InChIKey: GFHJYPQZBBHOCC-PMACEKPBSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Mus musculus
UniProt: Q8BH82
Assay: Inhibition of full length mouse NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 1819.7 nM (pChEMBL 5.739999771118164)
Descriptors: MW 421.55, ALogP 2.57, HBA 6, HBD 2, PSA 81.59, QED 0.75
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3ccc(N4CCN(C)CC4)cc3)oc12
InChIKey: XXGYKUVWHMEKFY-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 using 7-ethoxyresorufin as substrate after 15 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 460.53, ALogP 4.39, HBA 7, HBD 0, PSA 64.38, QED 0.41
Compound (SMILES): CC(C)(C(=O)O)c1ccc(-c2cnc(N)c(-c3ccc(Cl)cc3)c2)cc1
InChIKey: NWTYEXPPVFBYDG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95819
Assay: Inhibition of MAP4K4 in human GripTite 293 MSR cells assessed as reduction in TRAF2 Ser/Thr phosphorylation incubated for 1.5 hrs by ELISA
Measurement: IC50 = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 366.85, ALogP 5.01, HBA 3, HBD 2, PSA 76.21, QED 0.68
Compound (SMILES): Cc1ncnc(C2CC2)c1-c1ncc2nc(NCc3ccc(S(C)(=O)=O)cn3)c(=O)n([C@@H](C)C3CC3)c2n1
InChIKey: HVVHIBHBDCYLDI-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human PBMC assessed as inhibition of IL-22 production
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 532.63, ALogP 3.21, HBA 11, HBD 1, PSA 145.51, QED 0.36
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(F)cc2)cc1
InChIKey: ACOLSUZRXNFSQW-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant full length human HDAC6 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 6.77 nM (pChEMBL 8.170000076293945)
Descriptors: MW 274.25, ALogP 2.2, HBA 3, HBD 3, PSA 78.43, QED 0.59
Compound (SMILES): O=C(/C(=N/O)Nc1ccc(F)c(Br)c1)c1cncs1
InChIKey: CPKUGJMEEMFIAF-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 344.17, ALogP 3.13, HBA 5, HBD 2, PSA 74.58, QED 0.29
Compound (SMILES): COc1c(C)c2c(c(O)c1CCCC(=O)Nc1ccc(Cl)cc1)C(=O)OC2
InChIKey: LFJUBVFDMDSVNT-UHFFFAOYSA-N
Target: Inosine-5'-monophosphate dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P12268
Assay: Inhibition of human IMPDH2 expressed in Escherichia coli assessed as apparent inhibition constant using NAD as substrate by fluorescence assay
Measurement: Ki = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 389.84, ALogP 3.99, HBA 5, HBD 2, PSA 84.86, QED 0.73
Compound (SMILES): CNC(=O)c1nn(C)c2ccc(Nc3nccc(-n4cc(N[C@@H]5CCCNC5)c(C)n4)n3)cc12
InChIKey: CGMCYALTKDQISD-MRXNPFEDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG assessed as tail current by plate-based planar patch clamp assay
Measurement: IC50 > 39000 nM (pChEMBL 4.408999919891357)
Descriptors: MW 460.55, ALogP 2.12, HBA 10, HBD 4, PSA 126.61, QED 0.34
Compound (SMILES): Cc1ccc(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CCC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)s1
InChIKey: LBOHZVFKDXCHAX-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 646.79, ALogP 6.18, HBA 8, HBD 2, PSA 128.17, QED 0.18
Compound (SMILES): N=C(N)NCCCCCNC(=O)NC[C@H](NC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1)C(=O)O
InChIKey: ZEDVVTNZWFMRKR-IRXDYDNUSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta3 integrin (unknown origin) expressed in human SW480 cells transfected with human beta3 assessed as inhibition of cell adhesion to fibrinogen incubated for 60 mins by crystal violet staining based analysis
Measurement: IC50 >= 6800 nM (pChEMBL 5.166999816894531)
Descriptors: MW 511.61, ALogP -0.64, HBA 6, HBD 7, PSA 206.81, QED 0.1
Compound (SMILES): O=C(Nc1ccc2c(c1)OCCO2)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: UYXVOXQMQIUENM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 469.55, ALogP 4.63, HBA 6, HBD 2, PSA 92.37, QED 0.44
Compound (SMILES): O=C(Nc1c[nH]nc1-c1nc(-c2ccc(CN3CCOCC3)cc2)c[nH]1)c1cccc(Cl)c1
InChIKey: OMUPVSAQBBZOJH-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) incubated for 40 mins in presence of ATP by Kinase-glo luminescence assay
Measurement: IC50 = 939 nM (pChEMBL 6.03000020980835)
Descriptors: MW 462.94, ALogP 4.2, HBA 5, HBD 3, PSA 98.93, QED 0.4
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc(C(C)C)cc1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: KXYZXPAKZCKVCR-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 454.55, ALogP 5.79, HBA 4, HBD 0, PSA 40.8, QED 0.36
Compound (SMILES): O=C(N/N=C/c1ccccc1O)N1CCN(c2ccccn2)CC1
InChIKey: ARPWBQZXQIRDJX-CPNJWEJPSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 325.37, ALogP 1.65, HBA 5, HBD 2, PSA 81.06, QED 0.66
Compound (SMILES): COc1ccccc1C(=O)N1CCC[C@H](c2ccnc3ncnn23)C1
InChIKey: BSZQESOEXLPIBQ-ZDUSSCGKSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of 6xHis-tagged human recombinant PDE3B expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 3388 nM (pChEMBL 5.46999979019165)
Descriptors: MW 337.38, ALogP 2.15, HBA 6, HBD 0, PSA 72.62, QED 0.73
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)nc2C(F)F)nc(N2CCOCC2)n1
InChIKey: BSJSHEXWIGDLOO-SNVBAGLBSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Displacement of alexa fluor 647-labeled kinase tracer 314 from recombinant N-terminal His6-tagged p110alpha (unknown origin) by TR-FRET assay
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 408.41, ALogP 0.91, HBA 10, HBD 1, PSA 115.41, QED 0.78
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CC(F)F)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: IDFGVAKRSVUJAR-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 741 nM (pChEMBL 6.130000114440918)
Descriptors: MW 604.61, ALogP 4.78, HBA 7, HBD 2, PSA 128.17, QED 0.22
Compound (SMILES): N#C[C@@H]1CC(F)(F)CN1C(=O)CNC(=O)c1csc(CS(=O)(=O)c2ccc(C(F)(F)F)cc2)n1
InChIKey: NFVMOVDFHPHEHQ-LBPRGKRZSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 522.48, ALogP 2.63, HBA 7, HBD 1, PSA 120.23, QED 0.58
Compound (SMILES): O/N=C/c1cc(Cl)cc(CN2CCN(c3ccncc3)CC2)c1O
InChIKey: HSRDSKPYSLWCCY-RGVLZGJSSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Binding affinity to DFP-inhibited human erythrocyte AChE assessed as dissociation constant preincubated with DFP for 15 mins followed by compound and acetylthiocholine addition and measured every 5 to 10 mins for 120 mins by DTNB based Ellman's method
Measurement: Kd = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 346.82, ALogP 2.57, HBA 6, HBD 2, PSA 72.19, QED 0.51
Compound (SMILES): O=C(Nc1cncc(-c2cnc3[nH]nc(-c4cc5cccnc5[nH]4)c3c2)c1)c1ccccc1
InChIKey: AFBARBOQEJYQMP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 431.46, ALogP 4.82, HBA 5, HBD 3, PSA 112.24, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#CC4CC45CC5)c3)nn(-c3nc(C(=O)O)cs3)c2CCC2CC2)cc1F
InChIKey: IWLRASIOXMYZEJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 459 nM (pChEMBL 6.340000152587891)
Descriptors: MW 616.74, ALogP 5.57, HBA 7, HBD 2, PSA 128.17, QED 0.24
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC(CO)C1
InChIKey: ZRVVOMWYBLFQTG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 616.6 nM (pChEMBL 6.210000038146973)
Descriptors: MW 302.42, ALogP 2.06, HBA 3, HBD 1, PSA 43.78, QED 0.93
Compound (SMILES): COc1ccn2c(=O)n(CC(=O)N[C@@H](C)c3ccc(OC(F)(F)F)cc3)nc2n1
InChIKey: VSIGLNNKFPHDNS-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 411.34, ALogP 1.68, HBA 8, HBD 1, PSA 99.75, QED 0.66
Compound (SMILES): CNc1cc(F)cc2cc(C(=O)Nc3ccc(C(=O)O)cc3CN(CCO)C3CCCCC3)c(=O)[nH]c12.Cl
InChIKey: NMFDMALDUNWPKI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by Q-patch clamp assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 510.57, ALogP 3.79, HBA 6, HBD 5, PSA 134.76, QED 0.3
Compound (SMILES): CC1(C(=O)N2CCC[C@@H](c3nc(-c4ccc(C(=O)Nc5cc(C(F)(F)F)ccn5)c(Cl)c4)c4c(N)nccn34)C2)COC1
InChIKey: PLYCDYCABTZOTF-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Btk Enzyme Activity Assay C: BTK enzymatic activity was determined with the LANCE (Lanthanide Chelate Excite) TR-FRET (Time-resolved fluorescence resonance energy transfer) assay. In this assay, the potency (IC50) of each compound was determined from an eleven point (1:3 serial dilution; final compound concentration range in assay from 1 μM to 0.017 nM) titration curve using the following outlined procedure. To each well of a black non-binding surface Corning 384-well microplate (Corning Catalog #3820), 5 nL of compound (2000 fold dilution in final assay volume of 10 μL) was dispensed, followed by the addition of 7.5 μL of 1× kinase buffer (50 mM Hepes 7.5, 10 mM MgCl2, 0.01% Brij-35, 1 mM EGTA, 0.05% BSA & 1 mM DTT) containing 5.09 pg/μL (66.67 pM) of BTK enzyme (recombinant protein from baculovirus-transfected Sf9 cells: full-length BTK, 6HIS-tag cleaved). Following a 60 minute compound & enzyme incubation, each reaction was initiated by the addition of 2.5 μL 1× kinase buffer containing 8 μM biotinylated A5 peptide (Biotin-EQEDEPEGDYFEWLE-NH2), and 100 μM ATP. The final reaction in each well of 10 μL consists of 50 pM hBTK, 2 μM biotin-A5-peptide, and 25 μM ATP. Phosphorylation reactions were allowed to proceed for 120 minutes. Reactions were immediately quenched by the addition of 20 uL of 1× quench buffer (15 mM EDTA, 25 mM Hepes 7.3, and 0.1% Triton X-100) containing detection reagents (0.626 nM of LANCE-Eu-W1024-anti-phospho Tyrosine antibody, PerkinElmer and 86.8 nM of Streptavidin-conjugated Dylight 650, Dyomics/ThermoFisher Scientific). After 60 minutes incubation with detection reagents, reaction plates were read on a PerkinElmer EnVision plate reader using standard TR-FRET protocol. Briefly, excitation of donor molecules (Eu-chelate:anti-phospho-antibody) with a laser light source at 337 nm produces energy that can be transferred to Dylight-650 acceptor molecules if this donor:acceptor pair is within close proximity. Fluorescence intensity at both 665 nm (acceptor) and 615 nm (donor) are measured and a TR-FRET ratio calculated for each well (acceptor intensity/donor intensity). IC50 values were determined by 4 parameter robust fit of TR-FRET ratio values vs. (Log10) compound concentrations.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 614.03, ALogP 5.04, HBA 8, HBD 2, PSA 127.74, QED 0.32
Compound (SMILES): CCCCC(Nc1nc2nn(C)cc2c2nc(-c3ccco3)nn12)C(=O)OCC
InChIKey: DEXIRCWPIAOKEJ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 551 nM (pChEMBL 6.260000228881836)
Descriptors: MW 397.44, ALogP 2.8, HBA 10, HBD 1, PSA 112.37, QED 0.45
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc([N+](=O)[O-])cc2)cc1
InChIKey: UMYGCMORXGSBRC-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 74.1 nM (pChEMBL 7.130000114440918)
Descriptors: MW 443.46, ALogP 0.81, HBA 7, HBD 4, PSA 190.6, QED 0.34
Compound (SMILES): CNC(=O)N1CCCc2ccc(NC(=O)c3cccc(-c4ccncc4)c3)cc21
InChIKey: FKQOEFTVOPIHMO-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Inhibition of CBP BRD (unknown origin) by TR-FRET assay
Measurement: IC50 = 63.3 nM (pChEMBL 7.199999809265137)
Descriptors: MW 386.46, ALogP 4.09, HBA 3, HBD 2, PSA 74.33, QED 0.71
Compound (SMILES): CO[C@]12C=CC3(C[C@@H]1C(C)(C)O)[C@H]1Cc4ccc(O)c5c4[C@]3(CCN1C)[C@@H]2O5
InChIKey: ZGKVSNGVCSJFTE-LEBBCELKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]HS665 from KOR in guinea pig brain membranes measured after 45 mins by scintillation counting method
Measurement: Ki = 2.992 nM (pChEMBL 8.520000457763672)
Descriptors: MW 383.49, ALogP 2.38, HBA 5, HBD 2, PSA 62.16, QED 0.77
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cc(OC3COC3)ccn2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: YTFTVXGKMYSGAV-LBPRGKRZSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 452.39, ALogP 2.05, HBA 8, HBD 1, PSA 96.09, QED 0.59
Compound (SMILES): N#C[C@@H]1CC(F)(F)CN1C(=O)CNC(=O)c1csc(Cc2ccccc2I)n1
InChIKey: GRAXWJMKESEPHA-LBPRGKRZSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 516.31, ALogP 2.83, HBA 5, HBD 1, PSA 86.09, QED 0.62
Compound (SMILES): O=C(O)c1cccc(Nc2ccc([N+](=O)[O-])c3c([N+](=O)[O-])cccc23)c1
InChIKey: DEBLYSMOATYNAJ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of human AKR1C3 using S-tetralol as substrate in presence of NADP by fluorescence method
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 353.29, ALogP 4.1, HBA 6, HBD 2, PSA 135.61, QED 0.52
Compound (SMILES): CN1CCN(C(=O)c2cc3c(s2)CCCC3)CC1c1ccnc2ncnn12
InChIKey: RIMYRYFPLGXSJI-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of 6xHis-tagged human recombinant PDE3B expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 5495 nM (pChEMBL 5.260000228881836)
Descriptors: MW 382.49, ALogP 2.19, HBA 7, HBD 0, PSA 66.63, QED 0.68
Compound (SMILES): O=S(=O)(N[C@@H]1CCN(CCCc2noc3ccccc23)C1)c1ccc(F)cc1
InChIKey: XIRROHSGQGQXTD-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from recombinant human 5HT7 receptor expressed in CHOK1 cell membranes measured after 120 mins by microbeta counting method
Measurement: Ki = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 403.48, ALogP 2.95, HBA 5, HBD 1, PSA 75.44, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(O[C@@H]2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)c(F)c1
InChIKey: RCQGNGSBZNZXOV-SJLPKXTDSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin)
Measurement: IC50 = 786 nM (pChEMBL 6.110000133514404)
Descriptors: MW 505.98, ALogP 6.34, HBA 5, HBD 3, PSA 91.93, QED 0.25
Compound (SMILES): O[C@@H]1[C@H](O)CO[C@H]1Cn1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21
InChIKey: YNJLPUNKRNXONY-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Antagonist activity at PPARdelta LBD (unknown origin) assessed as increase in recruitment of SMRT ID2 corepressor peptide by TR-FRET assay
Measurement: EC50 = 20200 nM (pChEMBL 4.699999809265137)
Descriptors: MW 501.71, ALogP 1.82, HBA 8, HBD 3, PSA 105.32, QED 0.36
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(F)F
InChIKey: IVBCTFVBWGUGKC-DXPJPUQTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Binding Assay: hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials [Sanguinetti et al., Nature, 2006, 440, 463-469.] and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 487.57, ALogP 4.63, HBA 5, HBD 2, PSA 56.42, QED 0.46
Compound (SMILES): Cn1cc(-c2cc(C(C)(C)O)ccc2OC2CC2)c2cc(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)[nH]c2c1=O
InChIKey: VLSNXLPXZLYNBB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 605.7, ALogP 5.07, HBA 7, HBD 5, PSA 151.47, QED 0.15
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC1
InChIKey: VDGCBKQFUSCJOT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1698.24 nM (pChEMBL 5.769999980926514)
Descriptors: MW 244.34, ALogP 2.06, HBA 2, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): CC(C)(C)c1n[nH]c2c1C(c1ccccc1OCCS(C)(=O)=O)N(c1ccc(-c3ccon3)cc1)C2=O
InChIKey: ZLCFGJCVZRSHRY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.61, ALogP 4.54, HBA 7, HBD 1, PSA 118.39, QED 0.38
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1cccc(C)c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: DXPKATIYYADFAW-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 14100 nM (pChEMBL 4.849999904632568)
Descriptors: MW 426.49, ALogP 4.98, HBA 4, HBD 0, PSA 40.8, QED 0.43
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: QKNTUQSKNADJQQ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX2 from human adenosine receptor A2A expressed in HEK293 cell membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 504.57, ALogP 6.33, HBA 7, HBD 1, PSA 90.02, QED 0.3
Compound (SMILES): CCOC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(F)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: JOXIPFXPBCNFCC-RUZZFIIFSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide from human adrenergic A3 receptor expressed in CHO cell membranes assessed as inhibitor constant by radio ligand binding assay
Measurement: Ki = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 457.49, ALogP 1.31, HBA 10, HBD 3, PSA 122.39, QED 0.4
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(NC(=O)CCCNc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)cc1
InChIKey: JDVCZYIRYRWVJK-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 insect cells using Boc-Lys(epsilon-Ac)-AMC as substrate measured after 90 mins by fluorescence assay
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 568.59, ALogP 2.75, HBA 8, HBD 5, PSA 179.8, QED 0.15
Compound (SMILES): CC(C)(NC(=O)[C@H]1CN(C2CCCCC2)CC[C@@H]1NC(=O)c1cc(-c2ccc(F)cc2F)on1)c1ccccn1
InChIKey: RAIGYWMMZVOOQS-UPVQGACJSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: In Vitro Assay: Tango CXCR7-bla U2OS cells are detached from culture dishes with 0.05% trypsin-EDTA and collected in growing medium (McCoy's 5A 90% (v/v), dialyzed FCS 10% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), 1 mM sodium pyruvate, P/S 1% (v/v) 50 μg/ml Hygromycin, 100 μg/ml Geneticin, 200 μg/ml Zeocin), spinned down and resuspended in assay medium (McCoy's 5A 90% (v/v), dialyzed FCS 1% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), P/S 1% (v/v)). 10′000 cells per well (in 30 μl) are seeded in a 384 well plate (black-walled, clear bottom). The plate is incubated at 37° C./5% CO2 for 24 hours. Test compounds are dissolved to 10 mM in DMSO and serially diluted in DMSO to 500× of the final concentration for dose response curves. Compounds are then diluted 1:100 in assay medium to 5× of the final concentration. 10 μl/well of diluted compounds are added to the assay plate and incubated for 15 minutes at 37° C. Thereafter CXCL12/SDF1-α is diluted in assay medium to 5× of the final concentration (its EC80 value for receptor activation) and 10 μl/well are added to the assay plate. The agonist leads to activation of the receptor and therefore to b-arrestin recruitment. Compounds acting as antagonists reduce this activation. The plate is incubated for 22 hrs at 37° C. 10 μl/well of detection reagent (LiveBLAzer-FRET BIG (CCF4-AM) substrate) is transferred to the assay plate and the plate is incubated for 2 hours at room temperature protected from light. Fluorescent counts are determined (Scan1: Ex 409/20 nm, Em 460/30 nm, Scan 2: Ex 409/20 nm, Em 530/30 nm).
Measurement: IC50 = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 551.64, ALogP 4.82, HBA 6, HBD 2, PSA 100.36, QED 0.44
Compound (SMILES): Cc1[nH]c(C(=O)Nc2ccc(C(=O)NCC(=O)O)cc2OC2CCN(C(=O)OC(C)(C)C)CC2)c(Cl)c1Cl
InChIKey: SWCZIYPIOLKCKW-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase using biotinylated oligonucleotide as substrate incubated for 30 mins in presence of ATP by fluorescence-based microplate reader assay
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 569.44, ALogP 4.47, HBA 6, HBD 4, PSA 150.06, QED 0.38
Compound (SMILES): CS(=O)(=O)CCNC(=O)C(O)c1ccc2c(c1)CCc1c(-c3noc(-c4ccccc4)c3C(F)(F)F)noc1-2
InChIKey: HFVGEVPZXZGOMH-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at human S1P3 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgamma-S binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 561.54, ALogP 3.98, HBA 8, HBD 2, PSA 135.53, QED 0.35