lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc2ncccc2c1-c1cc(-c2c(C)noc2C)cc2nc(C3CC3)[nH]c12
InChIKey: KHQQNXFBTALTQF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Amplified Luminescent Proximity Homogeneous Assay (ALPHA): Binding of the bromodomain BRD4-I to an acetylated histone H4 peptide was measured using a bead-based Amplified Luminescent Proximity Homogeneous Assay (ALPHA). The synthetic peptide containing amino acids 1-18 of histone H4 was acetylated at lysine 5, 8, 12, 16 and conjugated to biotin (SGRGACKGGACKGLGACKGGAACKRH-GSGSK-biotin[SEQ ID NO:1]) was purchased from Millipore. BRD4-I was expressed and purified from Escherichia coli as an N-terminal His6-tagged protein. Nickel-Chelate ALPHA acceptor beads (Perkin Elmer) were used to specifically bind BRD4-1 and ALPHA streptavidin donor beads (Perkin Elmer) were used because they specifically recognized the biotinylated H4 peptide. Binding of BRD4-1 to the peptide resulted in proximity of the donor and acceptor beads which leads to an increase in ALPHA signal whereas disruption of this protein-peptide interaction with a small molecule inhibitor resulted in a decrease in ALPHA signal. Assays were performed in 50 mM Hepes (pH 7.5), 150 mM NaCl, 0.1 mg/ml BSA, 0.01% (v/v) Brij, 0.5% (v/v) DMSO, 200 nM H4 peptide and 15 nM of BRD4-1 protein. After an assay reaction time of 60 minutes at 25° C., binding was measured with 20 ug/ml streptavidin donor beads and 20 ug/ml nickle-chelate acceptor beads. ALPHA signal was detected on an Envision plate reader (Ex: 320 nm; Em: 570 nm; Ex time: 180 ms). Data were normalized based on a positive (2 uM I-BET) and negative (DMSO) controls and IC50 values were calculated from the fit of the dose-response curves to a four-parameter equation. All IC50 values represent geometric mean values of a minimum of four determinations.
Measurement: IC50 = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 394.48, ALogP 6.24, HBA 4, HBD 1, PSA 67.6, QED 0.39
Compound (SMILES): Cn1nc(C2CCN(C(=O)CC(=O)O)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
InChIKey: LLGDRAUZZHUOQT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: In Vitro Enzyme Inhibition Assay: The inhibition of PI3K-beta, PI3K-alpha, PI3K-gamma and PI3K-delta was evaluated in a Kinase Glo based enzyme activity assay using human recombinant enzymes. Compounds in 100% DMSO were added to assay plates by acoustic dispensing. PI3K enzyme was added in a Tris buffer (50 mM Tris pH7.4, 0.05% CHAPS, 2.1 mM DTT, and 10 mM magnesium chloride) and allowed to preincubate with compound for 20 minutes prior to addition of substrate solution containing PIP2 and ATP. The enzyme reaction was stopped after 80 minutes by the addition of Kinase Glo detection solution containing Lucferin and Luciferase (from Kinase Glo® Plus Luminecent Kinase Assay kit (Promega #V3772). Plates were left for 30 minutes at room temperature then read on a Pherastar Instrument with a standard Luminescence filter block. The final concentration of DMSO, ATP and PIP2 in the assay were, 1%, 8 uM, and 80 uM respectively.
Measurement: IC50 = 1520 nM (pChEMBL 5.820000171661377)
Descriptors: MW 469.51, ALogP 1.38, HBA 11, HBD 2, PSA 179.04, QED 0.52
Compound (SMILES): N#Cc1nc(Nc2ccc([N+](=O)[O-])cc2)nc(NC2CCCCC2)n1
InChIKey: KJSQAFPATOUENW-UHFFFAOYSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of human cathepsin S using Z-LR-AMC as substrate after 30 mins by spectromicrofluorimetric method
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 339.36, ALogP 3.14, HBA 8, HBD 2, PSA 129.66, QED 0.63
Compound (SMILES): OC(CN[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)(c1cccnc1)C(F)(F)F
InChIKey: SQWIAXGMZFHLAX-WBEUYKKISA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 445.45, ALogP 3.07, HBA 7, HBD 3, PSA 104.02, QED 0.44
Compound (SMILES): NC(=O)C12CC3CC(C1)C(OC(=O)N1CCC(c4ncc(Cl)cn4)C1)C(C3)C2
InChIKey: DJVOJGHZDVCWOV-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: Inhibition of microsomal preparations of 11.beta.-HSDl by compounds of the present invention, as described essentially previously (K. Solly, SS Mundt, HJ Zokian, GJ Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384) was measured. All reactions were carried out in a clear flexible PET Microbeta plates 96-well at room temperature (PerkinElmer). Assay, substrate solution (50mM HEPES, pH7.4,100mM KCl, 5mM NaCl, 2mM MgCl 2, 2mM NADPH and 160nM [3 H] cortisone (1Ci / mmol)) a 49ul and distribution, and starting from the 0.1mM on to start by combining the semi-log (half-log) multiple of the incremental test compound 1uL in DMSO previously diluted (8 points). After pre-incubation of 10 minutes, incubated human 11-HSD1 overexpress the enzyme containing CHO cells isolated from microsomes solution 50uL.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 404.9, ALogP 2.74, HBA 5, HBD 1, PSA 98.41, QED 0.83
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccc(Cl)cc3)CC1)C2
InChIKey: VGQNXCDLTRSTAF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured up to 3 mins by Ellman's method
Measurement: IC50 = 2860 nM (pChEMBL 5.539999961853027)
Descriptors: MW 413.95, ALogP 5.01, HBA 4, HBD 0, PSA 38.77, QED 0.67
Compound (SMILES): O=C(Cc1ccc(Cl)cc1Cl)NC1CCOc2ncccc21
InChIKey: BMKDSFJBRRVNJK-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Cell line generation was performed in general according to established molecular cloning protocols. Specifically, RNA was extracted from human whole blood using the Qiagen RNeasy kit (Qiagen, CH) according to the manufacturer's instructions. Subsequently cDNA was made (Superscript II, Invitrogen AG, CH) and the human P2X7 gene (genbank ref. BC011913) was amplified with the following primers: ATCGCGGCCGCTCAGTAAGGACTCTTGAAGCCACT and CGCCGCTAGCACCACCATGCCGGCCTGCTGCAGCTGCA. The amplified sequence was subsequently ligated into a pcDNA3.1 (+) NotI, NheI digested plasmid. Human embryonic kidney (HEK) cells (ATCC CRL-1573, Manassas, Va., USA) were transfected with the pcDNA3.1 (+). hP2X7 plasmid using lipofectamine 2000 (Invitrogen AG, CH) according to the manufacturer's instructions. Following a 24 h exposure to DNA, cells were trypsinized and re-seeded at low density in the presence of 250 ug Geneticin. Geneticin resistant cells were then selected during two consecutive rounds of cloning by serial limiting dilution with visual inspection.
Measurement: IC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 337.21, ALogP 3.57, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): COc1ccc(C(=O)n2c(-c3ccc(OC)cc3)nc3ccccc32)cc1
InChIKey: PXJXUUDEYSHZAX-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP-55940 from human recombinant CB1 receptor expressed in HEK293 cell membranes incubated for 1.5 hrs
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 358.4, ALogP 4.41, HBA 5, HBD 0, PSA 53.35, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccc(NS(=O)(=O)c2ccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)cc2)cc1
InChIKey: HTVKDECMTMXAPH-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of human Aurora kinase A (E122 to K401 residues) expressed in mammalian expression system by Z'LYTE assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 569.65, ALogP 4.81, HBA 8, HBD 3, PSA 136.63, QED 0.27
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(Cn2ccc3cc(/C=C/C(=O)NO)ccc32)c(F)c1
InChIKey: RPYILBLFWKTSJT-ONNFQVAWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 = 2030 nM (pChEMBL 5.690000057220459)
Descriptors: MW 621.62, ALogP 6.15, HBA 6, HBD 2, PSA 101.6, QED 0.09
Compound (SMILES): COc1cc(OCCN)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HWPCUDFQBWGXQP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.54, ALogP 3.92, HBA 8, HBD 1, PSA 91.32, QED 0.42
Compound (SMILES): CCO[C@H]1CC[C@]2(CC1)Cc1ccc(-c3cncc(C(F)(F)F)c3)cc1C21N=C(C)C(N)=N1
InChIKey: ROMALOVSXMWQTO-MOOVDDBPSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 456.51, ALogP 5.27, HBA 5, HBD 1, PSA 72.86, QED 0.68
Compound (SMILES): CCc1ccccc1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCCNC2)c1O
InChIKey: MKXPBYCTEVMLQI-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Antagonist activity at CXCR2 (unknown origin) expressed in CHO-K1 cells co-expressing Galpha-16 assessed as inhibition of IL8-induced calcium mobilization measured after 10 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 437.95, ALogP 3.78, HBA 5, HBD 4, PSA 107.53, QED 0.53
Compound (SMILES): c1cc2[nH]cc(-c3cncc(C4CC4)n3)c2cc1-c1nnc(N2CCNCC2)o1
InChIKey: JTESMRSKGHICMR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Enzyme Assay: The assay for the determination of Pim activity is based on the formation of phosphorylated biotinylated-BAD peptide at the Serine 112 residue (S112) and employs HTRF® (homogeneous time resolved fluorescence) technology to detect the product in a 96-well plate format. The phosphorylation of biotinylated-BAD (S112) peptide by full length recombinant Pim-1, Pim-2, or Pim-3 protein was detected with streptavidin:Allophycocyanin (APC) conjugate and a europium (Eu) labeled antibody directed against phosphorylated-BAD (S112). Excitation of Eu by a high energy laser light (337 nm) leads to a transfer of energy to the APC molecule, and results in an emission at 665 nm. The fluorescence is directly proportional to the amount of phosphorylated BAD peptide present in the reaction.Compounds were prepared in DMSO by conducting 3-fold serial dilutions to give a 10-point dosing curve having a high dose of 1 uM. A reference compound was included on each assay plate in order to validate that plate; on
Measurement: IC50 = 7.106 nM (pChEMBL 8.149999618530273)
Descriptors: MW 387.45, ALogP 2.96, HBA 7, HBD 2, PSA 95.76, QED 0.56
Compound (SMILES): COc1cc(Nc2nc(Cl)cc3c(C(C)C)n[nH]c23)cc(OC)c1OC
InChIKey: FUEDGAAZRJTKOK-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity to wild type A3R (unknown origin) expressed in CHO-K1 cells assessed as equilibrium binding affinity constant by nanoBRET assay
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 376.84, ALogP 4.5, HBA 6, HBD 2, PSA 81.29, QED 0.62
Compound (SMILES): CCC1(CC(C(=O)Nc2ccc(-c3noc(=O)[nH]3)cc2)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)COC1
InChIKey: GNLXHDHFJKLSJD-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 576.01, ALogP 4.39, HBA 9, HBD 2, PSA 152.24, QED 0.3
Compound (SMILES): c1ccc(-c2cc(CNc3nc(NCCN4CCCC4)cc(Nc4cc(C5CC5)n[nH]4)n3)on2)cc1
InChIKey: BIDWKKHFJJGGPB-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human IGF1R kinase domain (M954 to C1367 residues) tri-phosphorylated enzyme form expressed in baculovirus based expression system using poly-EY peptide incubated for 2 hrs by luciferase-luciferin coupled chemiluminescent assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 485.6, ALogP 4.6, HBA 9, HBD 4, PSA 119.82, QED 0.24
Compound (SMILES): COc1ccc(C(=O)C2CCN(C3CCN(Cc4nc5c(c(=O)[nH]4)CCC5)C3=O)CC2)cc1
InChIKey: IMXDGAQYSOUZNJ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Biochemical Assay: The autoparsylation activity of the TNKS 1/2 or PARP1/2 enzymes was measured by the liquid chromatography-mass spectrometry (LC/MS) detection of nicotinamide as readout. Compound activity in inhibiting the TNKS and PARP autoparsylation was evaluated by IC50 measurements. In the compound screening assays, the reaction is composed of 5 uL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 uM, 20 nM of purified enzyme, and 250 uM of p-NAD+ in the 1x Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 uL of 5x quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 uL of the 5x quenching solution per well was added prior to the addition of p-NAD+. The % Inhibition was calculated as: (Control-Sample)/(Control-Background)*100. "Control" is the average value of 8 wells without compound; and "Background" is the average of 8 wells mixed with 5x quenching solution measured prior to initiation of the reaction.
Measurement: IC50 = 29600 nM (pChEMBL 4.53000020980835)
Descriptors: MW 450.54, ALogP 1.96, HBA 6, HBD 1, PSA 95.6, QED 0.68
Compound (SMILES): O=C(COc1ccccc1-c1cc[nH]n1)NC[C@H](O)CN1CCc2ccccc2C1
InChIKey: BWYGXZCSXPRWTJ-IBGZPJMESA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Biochemical Assay: Molecular Biology: Full-length human PRMT5 (NM_006109.3) transcript variant 1 clone was amplified from a fetal brain cDNA library, incorporating flanking 5′ sequence encoding a FLAG tag (MDYKDDDDK) (SEQ ID NO.:4) fused directly to Ala 2 of PRMT5. Full-length human MEP50 (NM_024102) clone was amplified from a human testis cDNA library incorporating a 5′ sequence encoding a 6-histidine tag (MHHHHHH) (SEQ ID NO.:5) fused directly to Arg 2 of MEP50. The amplified genes were sublconed into pENTR/D/TEV (Life Technologies) and subsequently transferred by Gateway attL×attR recombination to pDEST8 baculvirus expression vector (Life Technologies).Protein Expression. Recombinant baculovirus and Baculovirus-Infected Insect Cells (BIIC) were generated according to Bac-to-Bac kit instructions (Life Technologies) and Wasilko, 2006, respectively. Protein over-expression was accomplished by infecting exponentially growing Spodoptera frugiperda (SF9) cell culture at 1.2×106 cell/ml with a 5000 fold dilution of BIIC stock. Infections were carried out at 27° C. for 72 hours, harvested by centrifugation, and stored at −80° C. for purification.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 406.49, ALogP 1.99, HBA 5, HBD 3, PSA 90.48, QED 0.53
Compound (SMILES): CN1CCN(c2ccc(-c3ccc4[nH]c5nccc(-c6ccc(C(=O)c7ccccc7)cc6)c5c4c3)cc2)CC1
InChIKey: VJSPNECZNBHJNW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant GST-tagged ALK L1196M mutant (1064 to 1427 residues) (unknown origin) expressed in Sf9 cells using TMB peptide as substrate preincubated for 10 mins followed by ATP addition and measured after 15 mins by ELISA analysis
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 522.65, ALogP 7.03, HBA 4, HBD 1, PSA 52.23, QED 0.25
Compound (SMILES): O=C(NCC(O)CN1CCc2ccccc2C1)c1cccc(-c2ccccn2)c1
InChIKey: IQOXVADYZAROMQ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of human full length FLAG-tagged PRMT5/human His6-tagged MEP50 expressed in baculovirus-infected Sf9 cells assessed as reduction in tritium incorporation into peptide substrate using human Histone H4 (1 to 15 residues) and [3H]SAM as substrate preincubated with enzyme and H4 for 30 mins followed by [3H]SAM addition and measured after 120 mins by radioactive flashplate assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 387.48, ALogP 2.9, HBA 4, HBD 2, PSA 65.46, QED 0.68
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2ccc(F)cc12
InChIKey: XSSUSSFECNXHAZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 302.35, ALogP 2.95, HBA 3, HBD 1, PSA 45.33, QED 0.89
Compound (SMILES): COc1ccc(C2CC(c3ccccc3OC)=NN2c2ccc(C(=O)O)cc2)cc1
InChIKey: SGXGRYNXXLPGLY-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Colorimetric Assay: The activities of COX-1 and COX-2 were measured after the addition of arachidonic acid and incubation at 25° C. for 5 min by absorbance at 590 nm as specified by the manufacturer.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 402.45, ALogP 4.76, HBA 5, HBD 1, PSA 71.36, QED 0.64
Compound (SMILES): O=c1ccoc2cc(OCc3ccc(F)cc3)ccc12
InChIKey: ZSNRPPMWDKPLRO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in insect cell microsomes using kynuramine as substrate assessed as decrease in 4-hydroxyquinoline production incubated for 20 mins by fluorescence spectrophotometry
Measurement: IC50 = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 270.26, ALogP 3.51, HBA 3, HBD 0, PSA 39.44, QED 0.73
Compound (SMILES): Cc1c(Cc2ccc(F)cc2F)nnc(N2CCN(c3ncc(C(C)(C)O)c(C(F)(F)F)n3)[C@H](C)C2)c1C
InChIKey: UAIAGAAYSWOKMP-CQSZACIVSA-N
Target: Protein smoothened (SINGLE PROTEIN), Mus musculus
UniProt: P56726
Assay: Displacement of radio-labeled smoothened agonist from mouse Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 536.55, ALogP 4.71, HBA 7, HBD 1, PSA 78.27, QED 0.47
Compound (SMILES): COc1ccc(C(F)(F)F)cc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: MYSWDWTYUYBQPI-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro Assay: HEK 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the IonWorks® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation. Cells were held at −110 mV for three seconds (Nav 1.7) or half a second (Nav 1.5) from a holding voltage of −15 mV, then put through a series of 26 pulses of 150 msec duration to −20 mV at a frequency of 5 Hz. Cells were then left unclamped for a period of 3 to 8 minutes while a single concentration of test compound was added. Cells were then reclamped and put through the same voltage protocol. Current at the end of the 26th pulse to −20 mV was subtracted from the peak current evoked by the 26th pulse to −20 mV to correct for leak current.
Measurement: IC50 = 5060 nM (pChEMBL 5.300000190734863)
Descriptors: MW 471.48, ALogP 4.5, HBA 7, HBD 1, PSA 80.76, QED 0.59
Compound (SMILES): CNc1nccc(-c2cn(C(C)C)nc2-c2cc(Cl)cc(NS(C)(=O)=O)c2F)n1
InChIKey: LDNRMMCYKPMHQR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of IL1-beta-induced p38alpha phosphorylation in human A549 cells pre-incubated for 30 mins before IL1-beta stimulation and measured after 7 to 8 hrs post IL1-beta stimulation by Bright-Glo luciferase reporter gene assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 438.92, ALogP 3.79, HBA 7, HBD 2, PSA 101.8, QED 0.61
Compound (SMILES): COc1cc(-c2nn(Cc3cc4cccc(C)c4c(=O)n3-c3ccccc3F)c3ncnc(N)c23)ccc1Cl
InChIKey: QCWQFNBGKLOKTB-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 540.99, ALogP 5.54, HBA 8, HBD 1, PSA 100.85, QED 0.31
Compound (SMILES): COc1cccc(/C=C/c2n[nH]c3cc(-c4ccncc4)ccc23)c1
InChIKey: OGXAUYJGBCTBHK-VMPITWQZSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK4/cyclin D3 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 327.39, ALogP 4.8, HBA 3, HBD 1, PSA 50.8, QED 0.59
Compound (SMILES): C[C@H](NC(=O)C(=O)NC12CC3CC(CC(C3)C1)C2)C(=O)N[C@@H](CC(=O)O)C(=O)COP(=O)(c1ccccc1)c1ccccc1
InChIKey: JYCOKQSQAYKENG-BRVUZIAJSA-N
Target: Caspase-6 (SINGLE PROTEIN), Homo sapiens
UniProt: P55212
Assay: Inhibition of recombinant MCH2 (unknown origin) pre-incubated for 60 mins with Acetyl-Tyr-Val-Ala-Asp-amino-4-methylcoumarin substrate followed by enzyme addition by fluorescence based assay
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 623.64, ALogP 2.05, HBA 7, HBD 4, PSA 167.97, QED 0.21
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)OC[C@H]1C[C@@]23CC[C@]1(OC)[C@@H]1Oc4c(O)ccc5c4[C@@]12CCN(CC1CC1)[C@@H]3C5
InChIKey: AGUKEFSLHJXTQC-WLQXWTRFSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Functional Assay: [35S]GTPgammaS functional assays were conducted using freshly thawed u-receptor membranes (Perkin Elmer, Shelton, Conn.). Assay reactions were prepared by sequentially adding the following reagents to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice (final concentrations indicated): membrane protein (0.026 mg/mL), saponin (10 mg/mL), GDP (3 mM) and [35S]GTPgammaS (0.20 nM; Perkin Elmer, Shelton, Conn.). The prepared membrane solution (190 ul/well) was transferred to 96-shallow well polypropylene plates containing 10 ul of 20x concentrated stock solutions of the agonist [D-Ala2, N-methyl-Phe4 Gly-ol5]-enkephalin (DAMGO) prepared in dimethyl sulfoxide (DMSO). Plates were incubated for 30 min at about 25° C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Perkin Elmer, Shelton, Conn.) using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by three filtration washes with 2001 of ice-cold binding buffer.
Measurement: EC50 = 5.04 nM (pChEMBL 8.300000190734863)
Descriptors: MW 510.68, ALogP 3.53, HBA 7, HBD 2, PSA 94.25, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(OC)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AHEDUFSEDRFCTH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)C3CCc4ccccc4C3)CC2)C1
InChIKey: MXLXKGHDGPYVBC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 520.64, ALogP 3.54, HBA 7, HBD 1, PSA 106.73, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccnc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CKXQGKOTLUERBE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.54, ALogP 4.63, HBA 8, HBD 0, PSA 78.19, QED 0.33
Compound (SMILES): O=S(=O)(Nc1ccc(Oc2ccccc2)cc1)c1cccc(C(F)(F)F)c1
InChIKey: PVKYGQVDOOMAHJ-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at human AR expressed in HEK293 cells measured after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 393.39, ALogP 5.3, HBA 3, HBD 1, PSA 55.4, QED 0.64
Compound (SMILES): CC1C[C@@H]2[C@H](CC[C@]3(C)C(c4ccncc4)=CC[C@@H]23)[C@@]2(C)CCNC(=O)C=C12
InChIKey: NWPAPVMBAZWICW-DLYNBCAFSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of CYP17 in human H295R cells assessed as decrease in testosterone levels after 24 hrs by ELISA
Measurement: IC50 <= 15 nM (pChEMBL 7.823999881744385)
Descriptors: MW 376.54, ALogP 5.01, HBA 2, HBD 1, PSA 41.99, QED 0.75
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3ccccc3C#N)CC2)C1
InChIKey: BVRPIDFGHQWSEA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 477.58, ALogP 3.28, HBA 8, HBD 1, PSA 113.45, QED 0.45
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IQAIXSLQDLQWKO-XERRXZQWSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 4677.35 nM (pChEMBL 5.329999923706055)
Descriptors: MW 500.53, ALogP 4.73, HBA 8, HBD 1, PSA 77.33, QED 0.32
Compound (SMILES): CCC1(NC(=O)OCc2ccccc2)CCCN(S(=O)(=O)CC2CCC(N(C)c3ncnc4[nH]ccc34)CC2)C1
InChIKey: PYVXUPZAXBIUIP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzymatic Assay: A peptide mobility shift assay was used to quantify the phosphorylation of the JAKtide (JAK2 and JAK3) or the IRS-1 peptide (JAK1 and Tyk2). Reactions were carried out in a 384-well plate (Matrical MP-101) in a 10 L total volume. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween-20, ATP (4 M for JAK2 and JAK3, 40 M for JAK1 and 7 M for Tyk2)), 2% DMSO and 1 M peptide substrate (JAKtide for JAK2 and JAK3 and IRS-1 peptide for JAK1 and Tyk2). Compounds were diluted serially in 100% dimethyl sulfoxide and tested in an 11 point dose response in duplicate or quadruplicate (200 nl of compound/DMSO was added per 10 L reaction). The reactions were initiated by the addition of enzyme to the final concentration of 2 nM JAK2, 1 nM JAK3, 12 nM Tyk2 or 20 nM JAK1. The assay was run for 240 minutes for JAK1, 150 minutes for JAK2, 90 minutes for JAK3 and 70 minutes for Tyk2.
Measurement: IC50 = 71.7 nM (pChEMBL 7.139999866485596)
Descriptors: MW 568.74, ALogP 4.45, HBA 7, HBD 2, PSA 120.52, QED 0.39
Compound (SMILES): CN1CCN(CCc2cn(CC3=CCC(C(=O)NO)C=C3)c3ccccc23)CC1
InChIKey: UDLAINZLDJPMES-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: HDAC Activity Assay: HDAC assay is performed using fluorescently-labeled acetylated substrate, which comprises an acetylated lysine side chain. After incubation with HDAC, deacetylation of the substrate sensitizes the substrate such that, in a second step, treatment with the detection enzyme produces a fluorophore. HDACs 1 and 6 were expressed as full length fusion proteins. Purified proteins were incubated with 50 μM fluorescently-labeled acetylated peptide substrate and test compound for 2 hours at RT in HDAC assay buffer containing 50 mM Tris-HCl (pH 8.0), 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1% DMSO, and 1% BSA. Reactions were terminated by the addition of the Developer after 2 hours, and the development of fluorescence signal, which was relative to the amount of deacetylated peptide, was monitored by time-course measurement of EnVision (PerkinElmer). The HDAC activity was estimated from the slope of time-course measurement of the fluorescence intensity.
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 394.52, ALogP 2.44, HBA 5, HBD 2, PSA 60.74, QED 0.58
Compound (SMILES): O=C(Nc1ccc(C2CCNC2)cc1)OCCc1cc(F)ccc1F
InChIKey: ZUHSZYHIYSSYLY-UHFFFAOYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay on Rat TAAR1: The TAAR1 radioligand 3[H](S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine (described in WO 2008/098857) was used at a concentration equal to the calculated Kd value, that was usually around 2.3 nM, resulting in the binding of approximately 0.2% of the radioligand and a specific binding representing approximately 85% of the total binding. Nonspecific binding was defined as the amount of 3[H](S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine bound in the presence of 10 μM unlabeled ligand. All compounds were tested at a broad range of concentrations (10 μM to 10 μM) in duplicates. The test compounds (20□ μl/well) were transferred into a 96 deep well plate (TreffLab), and 180 μl of HEPES-NaOH (20 mM, pH 7.4) containing MgCl2(10 mM) and CaCl2) (2 mM)(binding buffer), 300 μl of the radioligand 3[H](S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine at a concentration of 3.3×Kd in nM and 500 μl of the membranes (resuspended at 50 μg protein per ml) added. The 96 deep well plates were incubated for 1 hr at 4° C. Incubations were terminated by rapid filtration through Unifilter-96 plates (Packard Instrument Company) and glass filters GF/C (Perkin Elmer) presoaked for 1 hr in polyethylenimine (0.3%) and washed 3 times with 1 ml of cold binding buffer. After addition of 45 μl of Microscint 40 (PerkinElmer) the Unifilter-96 plate was sealed and after 1 hr the ratioactivity counted using a TopCount Microplate Scintillation Counter (Packard Instrument Company).
Measurement: Ki = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 346.38, ALogP 3.83, HBA 3, HBD 2, PSA 50.36, QED 0.86
Compound (SMILES): COC(c1ccccc1)C1CCN(S(=O)(=O)c2c(C)n[nH]c2C)CC1
InChIKey: FINZWOFOVHLTQE-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Biological Assay: The ability of a compound to block the intracellular release of calcium mediated by PK1 in RBL2H3 cells expressing human PKR1 receptors is determined as a measure of the compound's antagonist activity in vitro.Approximately 10,000 cells per assay well are seeded in normal culture medium in a 384 well plate (Corning). Twenty-four hours after seeding, the cells are loaded with a calcium sensitive fluorescent dye by replacing the culture medium with assay buffer (1× Hanks buffered saline, 25 mM HEPES, 0.1% w/v fatty acid free BSA (bovine serum albumin), pH 7.4) containing 1 mM probenecid and 1× Calcium 5 Reagent (Molecular Devices). Cells are incubated at 37° C. for 1 hour to allow for dye uptake.To test for antagonist activity, test compounds at a final concentration range between 0.32 nM-10 μM (diluted in assay buffer) are added to the assay wells and allowed to incubate for 10 minutes prior to stimulation with PK1. After incubation with test compounds the assay plate is placed in a FLIPR Tetra (Molecular Devices) and PK1 (diluted in assay buffer) is added at the determined EC80 concentration (final). Ligand-dependent changes in intracellular calcium levels are determined by measuring changes in fluorescence of the dye at 525 nM following to excitation at 485 nM.
Measurement: IC50 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 363.48, ALogP 2.81, HBA 4, HBD 1, PSA 75.29, QED 0.89
Compound (SMILES): C[C@@H]1CN(c2sc(C3COC3)nc2-c2nc3ccccc3[nH]2)CCN1C(=O)Cn1cnc2cccnc21
InChIKey: RWEYPYDCLNMMCX-MRXNPFEDSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Inhibition of CXCR3 receptor internalization in human venous whole blood incubated for 30 mins by flow cytometer analysis
Measurement: IC50 = 1154 nM (pChEMBL 5.940000057220459)
Descriptors: MW 514.62, ALogP 3.28, HBA 9, HBD 1, PSA 105.06, QED 0.38
Compound (SMILES): SC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: ACRMSFLLAJABLP-MGCOHNPYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 287.39, ALogP 2.81, HBA 5, HBD 2, PSA 58.87, QED 0.71
Compound (SMILES): CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCC(O)CC5)c([N+](=O)[O-])c4)c(Oc4ccc5[nH]ccc5c4)c3)CC2)=C(c2ccc(Cl)cc2)C1
InChIKey: YKGNPPDXOZOAQK-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64373
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki > 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 881.5, ALogP 9.39, HBA 10, HBD 4, PSA 170.14, QED 0.07
Compound (SMILES): NC(=O)c1cccc([C@H]2C[C@H]3CC[C@@H](C2)N3CCCN(Cc2ccccc2)C(=O)[C@@H](O)CO)c1.O=C(O)C(F)(F)F
InChIKey: DGTCPQZBMQEAFL-DKVOZMMNSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-diprenorphine from human mu opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 465.59, ALogP 2.27, HBA 5, HBD 3, PSA 107.1, QED 0.5
Compound (SMILES): Nc1n[nH]c2c1C(c1ccc(F)c(Cl)c1)c1c(N)n[nH]c1O2
InChIKey: UYZFCOLDZJOODH-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-induced human MDA-MB-231 cells using tryptophan as substrate preincubated for 4 hrs followed by substrate addition for 5 hrs by spectrophotometric method
Measurement: EC50 = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 320.71, ALogP 2.38, HBA 5, HBD 4, PSA 118.63, QED 0.43
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)c(OC)c4)nn32)CC1
InChIKey: UGBDLAMFDOZLBT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 501.59, ALogP 4.23, HBA 7, HBD 2, PSA 111.71, QED 0.47
Compound (SMILES): COc1nc2ccc(C(O)(c3ccc(Cl)cc3)c3cncn3C)cc2c(Cl)c1Cc1ccc(-n2cncn2)cc1
InChIKey: BCPPJFGMAGRVIG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: ThermoFluor® Assay: Bar-coded assay plates are robotically loaded onto a thermostatically controlled PCR-type thermal block and then heated at a typical ramp-rate of 1 °C./min for all experiments. Fluorescence was measured by continuous illumination with UV light (Hamamatsu LC6) supplied via fiber optic and filtered through a band-pass filter (380-400 nm; >6 OD cutoff). Fluorescence emission of the entire 384-well plate was detected by measuring light intensity using a CCD camera (Sensys, Roper Scientific) filtered to detect 500±25 nm, resulting in simultaneous and independent readings of all 384 wells. Images were collected at each temperature, and the sum of the pixel intensity in a given area of the assay plate was recorded versus temperature. Reference wells contained RORγt without compounds, and the assay conditions were as follows: 0.065 mg/mL RORγt, 60 μM 1,8-ANS, 100 mM Hepes, pH 7.0, 10 mM NaCl, 2.5 mM GSH, 0.002% Tween-20. Project compounds were arranged in a pre-dosed mother plate (Greiner Bio-one) wherein compounds are serially diluted in 100% DMSO by 1:2 from a high concentration of 10 mM over 12 columns within a series (column 12 is a reference well containing DMSO, no compound). The compounds were robotically dispensed directly into assay plates (1×=46 nL) using a Hummingbird capillary liquid handling instrument (Digilab). Following compound dispense, protein and dye in buffer was added to achieve the final assay volume of 3 μL, followed by 1 μL of silicone oil.
Measurement: Kd = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 571.47, ALogP 5.74, HBA 8, HBD 1, PSA 90.88, QED 0.26
Compound (SMILES): Cc1cc(C)cc(S(=O)(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(NC(=O)CCCNC(=N)N)cc2)C(=O)O)c1
InChIKey: SXKPBPZVSACQSN-GOTSBHOMSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell Adhesion Assay : A panel of cell lines and integrin ligands were developed to allow rapid examination of potency and specificity of inhibitors against all 8 integrins that recognize RGD sequences in ligands. A subset of these was used to generate the very encouraging data about 8 shown above. These cell lines were used to calculate IC50 concentrations for each inhibitor synthesized to rapidly generate structure activity information to drive subsequent modification and synthesis. Inhibitors were evaluated for showing better potency/selectivity in CCl4-induced liver fibrosis.
Measurement: IC50 = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 572.69, ALogP 1.47, HBA 6, HBD 6, PSA 194.78, QED 0.12
Compound (SMILES): c1cc2c(ncn3nnc(C4CCC(NCCN5CCOCC5)CC4)c23)[nH]1
InChIKey: FPLURTUHUZXJQT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 369.47, ALogP 1.55, HBA 7, HBD 2, PSA 83.37, QED 0.71
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCN5CCOCC5)c4)nc3c2)c1.Cl
InChIKey: PZJWQXFQJHDXPN-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.66, ALogP 4.78, HBA 9, HBD 0, PSA 77.77, QED 0.28