lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(OC)c(Cl)c(NC(=O)N(C)c2cc(Nc3ccccc3NC(=O)/C=C/Cl)ncn2)c1Cl
InChIKey: FJRNERRNFRDHLE-CMDGGOBGSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Kinase HotSpotâ¿¢ Assay: Compounds were profiled for FGFR inhibition activity at Reaction Biology Corporation (Malvern, Pa.) with their Kinase HotSpot assay. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.Recombinant FGFR1 (2.5 nM), FGFR2 (1 nM), FGFR3 (5 nM), or FGFR4 (12 nM) (Invitrogen) was prepared as a mixture with substrate KKKSPGEYVNIEFG (SEQ ID NO:1) (20 uM, FGFR1 substrate); and Poly [E,Y]4:1 (0.2 mg/ml, FGFR2,3,4 substrate)] in kinase reaction buffer (20 mM HEPES-HCl, pH 7.5, 10 mM MgCl2, 2 mM MnCl2, 1 mM EGTA, 0.02% Brij35, 0.1 mM Na3VO4, 0.02 mg/ml BSA, 2 mM DTT, and 1% DMSO). Compound was added to the enzyme/substrate mixture using acoustic technology (Labcyte Echo 550, Sunnyvale, Calif.) (see, Olechno et al., 2006, Improving IC50 results with acoustic droplet ejection. JALA 11, 240-246) and pre-incubated for 0, 15, or 60 minutes at room temperature. After compound pre-incubation, a mixture of ATP (Sigma-Aldrich) and 33P-γ-ATP (PerkinElmer) was added to a final concentration of 10 uM to initiate kinase reactions. Reactions were incubated for 120 minutes at room temperature and then spotted onto Whatman P81 ion exchange filter paper. Unbound phosphate was removed by extensively washing filters in 0.75% phosphoric acid. See, Anastassiadis et al., 2011, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29, 1039-1045.
Measurement: IC50 = 3920 nM (pChEMBL 5.409999847412109)
Descriptors: MW 551.82, ALogP 5.9, HBA 7, HBD 3, PSA 117.71, QED 0.3
Compound (SMILES): Cc1c(-c2ccc(C(F)(F)F)cc2)nnc(N2CCN(c3cnc(C(=O)N4CCOCC4)cn3)[C@H](C)C2)c1C
InChIKey: QTAZTPFWIUIJKI-QGZVFWFLSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 541.58, ALogP 3.76, HBA 8, HBD 0, PSA 87.58, QED 0.49
Compound (SMILES): N#CCC1(n2cc(C(N)=O)c(Nc3ccnc(F)c3)n2)CCC(Nc2ccc(Cl)cc2)CC1
InChIKey: PXPWBFKFZJATIY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 467.94, ALogP 4.58, HBA 7, HBD 3, PSA 121.65, QED 0.44
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)c(OC(F)(F)F)c2)cc(OC)c1
InChIKey: RNUOMGDKVIMQSL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 446.45, ALogP 4.03, HBA 6, HBD 2, PSA 85.89, QED 0.6
Compound (SMILES): C=Cc1ccc(-c2ccc3ncnc(Nc4ccc(CC#N)cc4)c3c2)cc1
InChIKey: IEAFYFVXFGKEPN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using diC8 PIP2 as substrate after 75 mins by ADP-glo assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 362.44, ALogP 5.75, HBA 4, HBD 1, PSA 61.6, QED 0.49
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4cccc(Br)c4)ccc3o2)cc1)c1cccc(Br)c1
InChIKey: XGTSPHSPZZFHEX-UHFFFAOYSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Inhibition of Mycobacterium tuberculosis His-tagged PtpB expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 30 mins by spectrophotometric method
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 663.37, ALogP 6.62, HBA 6, HBD 2, PSA 118.37, QED 0.2
Compound (SMILES): CCCN1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: CJQHDRRRDSNFOQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 477.39, ALogP 5.18, HBA 7, HBD 1, PSA 68.74, QED 0.48
Compound (SMILES): CN(CCO)C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: VNYUXOHMYSZACT-JOCQHMNTSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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 = 320 nM (pChEMBL 6.5)
Descriptors: MW 328.42, ALogP 1.8, HBA 6, HBD 2, PSA 82.34, QED 0.75
Compound (SMILES): Cc1n[nH]c2ncc(-c3ccc(Cl)c(NC(=O)/C=C/N(C)C)c3)cc12
InChIKey: HZXFVDJXOKIZTO-VOTSOKGWSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 = 739 nM (pChEMBL 6.130000114440918)
Descriptors: MW 355.83, ALogP 3.6, HBA 4, HBD 2, PSA 73.91, QED 0.7
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc4c(=O)n(Cc5ccc(F)cc5)nnc4cc3F)cc12
InChIKey: MKUFAWDAPBDDKS-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 2b by Taqman probe based RT-PCR analysis
Measurement: EC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 647.64, ALogP 5.09, HBA 8, HBD 1, PSA 127.4, QED 0.26
Compound (SMILES): CCN/C(=N\C#N)N1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: DSXVRWQRFDVWBE-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 530.42, ALogP 4.21, HBA 8, HBD 2, PSA 116.92, QED 0.26
Compound (SMILES): CCOc1cc(N2CCC(N3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IEXAEHAHMUVCRY-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 775.88, ALogP 7.69, HBA 10, HBD 2, PSA 103.16, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(CCn2cnnc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RUROKZDZIPBDNX-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 presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.51, ALogP 3.48, HBA 10, HBD 0, PSA 96.01, QED 0.35
Compound (SMILES): C[C@@H]1C[C@H](N)CN(c2ccncc2Nc2ncc3ccc(-c4c(F)cccc4F)nn23)C1
InChIKey: BYFQNMWZRKKFRI-CABCVRRESA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of Pim3 (unknown origin)
Measurement: IC50 = 0.027 nM (pChEMBL 10.569999694824219)
Descriptors: MW 435.48, ALogP 3.99, HBA 7, HBD 2, PSA 84.37, QED 0.5
Compound (SMILES): Cc1cccc(C)c1Nc1ccc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
InChIKey: ZUUYCPKOPFRHGK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Homogeneous Time Resolved Fluorescence Assay (HTRF): 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 μM. A reference compound was included on each assay plate in order to validate that plate; on one plate of every assay run, two additional reference compounds were included. The final buffer conditions were as follows: 60 mM Hepes, pH 7.0, 0.05% BSA, 2 mM DTT. Incubations were carried out at RT (22° C.) for 2 h for Pim-1, 1 hour and 30 min for Pim-3, and 45 min for Pim-2. The reaction was stopped by the addition of 3 mM EDTA, and fluorescence was measured by an HTRF® Rubystar microplate reader.
Measurement: IC50 = 73.9 nM (pChEMBL 7.130000114440918)
Descriptors: MW 382.47, ALogP 4.88, HBA 3, HBD 3, PSA 69.81, QED 0.47
Compound (SMILES): Cc1ccc(NC(=O)c2ccnc(C(C)(C)C#N)c2)cc1-c1cc(N2CCOCC2)c(=O)n(C)n1
InChIKey: LNLLSEAMZKXAPP-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Raf Activity: Raf and biotinylated Mek, kinase dead, were combined at 2× final concentrations in assay buffer (50 mM Tris, pH 7.5, 15 mM MgCl2, 0.01% BSA and 1 mM DTT) and dispensed 5 ml per well in assay plates (Greiner white 384 well assay plates #781207) containing 0.25 ml of 40× of a Raf kinase inhibitor test compound diluted in 100% DMSO. The plate was incubated for 60 minutes at room temperature. The Raf kinase activity reaction was started by the addition of 5 mL per well of 2×ATP diluted in assay buffer. After 3 hours (b-Raf(V600E)) or 1 hour (c-Raf). The reactions were stopped and the phosphorylated product was measured using a rabbit anti-p-MEK (Cell Signaling, #9121) antibody and the Alpha Screen IgG (ProteinA) detection Kit (PerkinElmer #6760617R), by the addition of 10 mL to the well of a mixture of the antibody (1:2000 dilution) and detection beads (1:2000 dilution of both beads) in Stop/bead buffer (25 mM EDTA, 50 mM Tris, pH 7.5, 0.01% Tween20). The additions were carried out under dark conditions to protect the detection beads from light. A lid was placed on top of the plate and incubated for 1 hour at room temperature, then the luminescence was read on a PerkinElmer Envision instrument. The concentration of each compound for 50% inhibition (IC50) was calculated by non-linear regression using XL Fit data analysis software.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 472.55, ALogP 3.04, HBA 8, HBD 1, PSA 113.14, QED 0.61
Compound (SMILES): Cc1ccn2c(-c3ccnc(Nc4cccc(OCCN(C)C)c4)n3)c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc2c1
InChIKey: GOSRBMJAHARBNL-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 619.68, ALogP 6.98, HBA 8, HBD 2, PSA 96.68, QED 0.17
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2cc1NC(=O)/C=C/CN1CCCCC1
InChIKey: BIHYRPIDCXHQKD-FMIVXFBMSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 561.69, ALogP 6.15, HBA 8, HBD 2, PSA 97.2, QED 0.2
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)Cl)cc1)c1cnc(N2C[C@@H](O)[C@@H](O)C2)c(-c2cncnc2)c1
InChIKey: INMCQZXOLSELDJ-HDICACEKSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Cellular Proliferation Assay: Test compounds were resuspended in DMSO at a concentration of 10 mM. A serial three-fold dilution of each compound with DMSO was performed in 384-well plates using the Janus Liquid Dispenser (PerkinElmer). Compound was delivered to the assay plates containing 2500 cells in a 50 μL volume via Acoustic delivery from an ATS-100 (EDC). For Ba/F3-BCR-ABL1-WT cell assays, 2 nL of each compound dilution was transferred to the assay plate for final assay concentrations of 0.4 μM, 0.13 μM, 0.044 μM, 0.015 μM, 0.005 μM, 0.001 μM, 0.00033 μM, 0.00011 μM, 0.000037 μM, 0.000012 μM. For Ba/F3-WT and Ba/F3-BCR-ABL1-T315I cell assays, 50 nL of each compound dilution was transferred to the assay plate for final assay concentrations of 10 μM, 3.33 μM, 1.11 μM, 0.37 μM, 0.12 μM, 0.041 μM, 0.014 μM, 0.0046 μM, 0.0015 μM, 0.00051 μM.Cells were incubated at 37° C. in a humidified environment with 5% car
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 477.86, ALogP 2.5, HBA 8, HBD 3, PSA 120.7, QED 0.46
Compound (SMILES): CC1Cc2c([nH]c3ccc([N+](=O)[O-])cc23)C2(CCC(c3ccccc3)(N(C)C)CC2)O1
InChIKey: AULHNJBHSOXPMG-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Binding Assay: The receptor affinity for the human mu-opiate receptor was determined in a homogeneous batch in microtitre plates. For this, dilution series of the particular spirocyclic cyclohexane derivative to be tested were incubated in a total volume of 250 ul for 90 minutes at room temperature with a receptor membrane preparation (15-40 ug protein per 250 ul incubation batch) of CHO-K1 cells, which express the human mu-opiate receptor (RB-HOM receptor membrane preparation of NEN, Zaventem, Belgium), in the presence of 1 nmol/l of the radioactive ligand [3H]-naloxone (NET719, NEN, Zaventem, Belgium) and of 1 mg WGA-SPA beads (wheat germ agglutinin SPA beads from Amersham/Pharmacia, Freiburg, Germany). 50 mmoles/l Tris-HCl supplemented with 0.05 wt. % sodium azide and with 0.06 wt. % bovine serum albumin was used as the incubation buffer. 25 umoles/l naloxone was additionally added for determination of the non-specific binding.
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 419.53, ALogP 5.26, HBA 4, HBD 1, PSA 71.4, QED 0.46
Compound (SMILES): O=C(c1ccco1)N1CCC(CCN2CCN(c3nsc4ccccc34)CC2)CC1
InChIKey: DGSJCQBCZUXHPR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from recombinant human 5-HT2A receptor expressed in HEK293 cell membranes after 60 mins by scintillation counting method
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 424.57, ALogP 3.95, HBA 6, HBD 0, PSA 52.82, QED 0.62
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3cc(N)nc(N)n3)n(-c3ccccc3)c(=O)c12
InChIKey: YUSGUEIYZQKLLY-AWEZNQCLSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/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 386.46, ALogP 3.43, HBA 7, HBD 3, PSA 111.85, QED 0.5
Compound (SMILES): CCN(c1cc(C#CC(C)(C)C)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: YKAMVMMDEBGNRT-DIVCQZSQSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 518.75, ALogP 5.33, HBA 4, HBD 2, PSA 68.44, QED 0.49
Compound (SMILES): CC(C)Cc1ccc(-c2onc3c2CCc2cc(CN4CC(C(=O)O)C4)ccc2-3)cc1C(F)(F)F
InChIKey: FYCCVYNLKDPHNG-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human S1P1 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgamma-S binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 484.52, ALogP 5.84, HBA 4, HBD 1, PSA 66.57, QED 0.48
Compound (SMILES): CCc1noc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)C3C)n1
InChIKey: AWKTWOOCLJMRQH-UHFFFAOYSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Binding Assay: The affinity of compounds of the invention for the NK-2 receptor was evaluated in CHO recombinant cells which express the human NK-2 receptor. Membrane suspensions were prepared from these cells. The following radioligand [125I]-Neurokinin A (PerkinElmer Cat#NEX252) was used in this assay. Binding assays were performed in a 25 mM HEPES/1 mM CaCl2/5 mM MgCl2/0.5% BSA/10 μg/ml saponin, at pH 7.4. Binding assays consisted of 25 μl of membrane suspension (approximately 3.75 μg of protein/well in a 96 well plate), 50 μl of compound or reference ligand (Neurokinin A) at increasing concentrations (diluted in assay buffer) and 0.1 nM [125I]-Neurokinin A. The plate was incubated 60 min at 25° C. in a water bath and then filtered over GF/C filters (Perkin Elmer, 6005174, presoaked in assay buffer without saponine for 2 h at room temperature) with a Filtration unit (Perkin Elmer). The radioactivity retained on the filters was measured by using the TopCount-NXT reader (Packard).
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 356.36, ALogP 2.25, HBA 7, HBD 0, PSA 89.94, QED 0.71
Compound (SMILES): Cc1c(Cc2ccc(F)cc2)nnc(N2CCN(c3ccc(C(F)(F)F)cn3)CC2)c1C
InChIKey: QTPBWEZKZBJJQL-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 445.46, ALogP 4.56, HBA 5, HBD 0, PSA 45.15, QED 0.55
Compound (SMILES): Brc1cc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)sc1Br
InChIKey: VZCRMSWRUSUSNR-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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 496.23, ALogP 4.57, HBA 6, HBD 1, PSA 62.11, QED 0.45
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCN)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NHSCTFBEZPHZRZ-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 presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.55, ALogP 2.74, HBA 9, HBD 2, PSA 120.42, QED 0.36
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CC[C@H]1C[C@@H](n1c(=O)c(N4CC[C@H]4C(=O)O)nc4ccccc41)C3)C2
InChIKey: ZHAKSJXRYXIJIF-GRMPTNSGSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro Delta-Opioid Receptor Binding Assay: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25 °C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50 °C. for 1-2 hours. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 11500 nM (pChEMBL 4.940000057220459)
Descriptors: MW 490.65, ALogP 4.44, HBA 6, HBD 1, PSA 78.67, QED 0.68
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(N(C)C)nc4)cc23)c1F
InChIKey: CNMJRJRTAYPAML-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of C-Raf1 (unknown origin) assessed as decrease in biotin-tagged MEK1 phosphorylation after 45 mins
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 500.53, ALogP 3.75, HBA 7, HBD 2, PSA 120.94, QED 0.35
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(C(=O)CCC(C)C)CCO1
InChIKey: NQRHMWLUXWPKIS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 533.46, ALogP 5.73, HBA 7, HBD 1, PSA 85.81, QED 0.38
Compound (SMILES): O=C(CCc1ccc(Cl)cc1CN1CCC[C@H]1c1nc(C(=O)NCCCCC2CCCCC2)co1)NS(=O)(=O)C(F)(F)F
InChIKey: XTSILTSKUZERSP-VWLOTQADSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Cell Based Assay: Ca2+ signaling studies were performed using a FLIPR TETRA system (Molecular Devices, Sunnyvale, Calif., USA) in the 384-format. This is a high-throughput instrument for cell-based assays to monitor Ca2+ signaling associated with GPCRs and ion channels. Cells were seeded at a density of 5×104 cells/well in BioCoat poly-D-lysine coated, black wall, clear bottom 384-well plates (BD Biosciences, Franklin lakes, NJ, USA) and allowed to attach overnight in an incubator at 37° C. The cells were then washed twice with HBSS-HEPES buffer (Hanks' balanced salt solution without bicarbonate and phenol red, 20 mM HEPES, pH 7.4) using an ELx405 Select CW Microplate Washer (BioTek, Winooski, Vt., USA). After 60 min of dye-loading in the dark using the Ca2+-sensitive dye Fluo-4AM (Invitrogen, Carlsbad, Calif., USA), at a final concentration of 2×10^−6M, the plates were washed 4 times with HBSS-HEPES buffer to remove excess dye and leaving 50 μl of buffer in each well. The plates were then placed in the FLIPR TETRA instrument and allowed to equilibrate at 37° C. AGN-211377 was added in a 25 μl volume to each well to give final concentrations of 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, and 30 μM; or 0.067 μM, 0.1 μM, 0.2 μM, 0.3 μM, 0.67 μM, and 1 μM for cells over-expressing TP receptors. After 4.5 minutes, a 7-point serial dilution of the standard agonist for the corresponding receptor, in a 25 μl volume was injected at the final concentrations from 10^−11M to 10^−5M in 10-fold serial dilution increments for cells expressing human recombinant DP1, EP1, EP2, EP3, EP4, FP, and IP receptors. The dose range for the standard agonist for human recombinant TP receptors was from 10^−12M to 10^−6M. HBSS-HEPES buffer was used as the negative control for the standard agonists. Cells were excited with LED (light emitting diode) excitation at 470-495 nm and emission was measured through an emission filter at 515-575 nm. Assay plates were read for 3.5 minutes using the FLIPRTETRA.
Measurement: EC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 647.16, ALogP 6.04, HBA 7, HBD 2, PSA 121.61, QED 0.25
Compound (SMILES): CC(C)(C)C(NC(=O)c1cc(OCC(F)(F)F)c(C2CC2)cn1)c1noc(N)n1
InChIKey: LEWWVOSURJRSLS-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1×HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37° C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30° C. for 30 min. Compounds were added to a final assay volume of 100 μl and incubated for 30 min at 30° C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 μl lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN3) and 50 μl detection solutions (20 μM mAb Alexa700-cAMP 1:1, and 48 μM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated as follows: FRET=T730-Alexa730-P(T645-B645) with P=Ru730-B730/Ru645-B645, where T730 is the test well measured at 730 nM, T645 is the test well measured at 645 nm, B730 and B645 are the buffer controls at 730 nm and 645 nm, respectively. cAMP content is determined from the function of a standard curve spanning from 10 μM to 0.13 nM cAMP.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.4, ALogP 3.38, HBA 7, HBD 2, PSA 116.16, QED 0.75
Compound (SMILES): CCN(CC)c1nc2ccc(C(O)(c3ccc(Cl)cc3)c3cncn3C)cc2c(Cl)c1Oc1ccccc1
InChIKey: QSNQBKVAYOUNKI-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORγt Reporter Assay: The reporter assay was performed by transiently transfecting HEK293T cells with 5 μg of pBIND-RORγt LBD or pBIND-RORγt LBD-AF2 and 5 μg pGL4.31 (Promega Cat no. C935A) using Fugene 6 (Invitrogen Cat no. E2691) at a 1:6 ratio of DNA: Fugene 6 in a T-75 flask in which cells were at least 80% confluent. Twenty four hours after bulk transfection, cells were plated into 96-well plates at 50,000 cells/well in phenol-red free DMEM containing 5% Lipid Reduced FCS and Pen/Strep. Six hours after plating, cells were treated with compounds for 24 hours. Media was removed and cells were lysed with 50 μL 1x Glo Lysis Buffer (Promega). Dual Glo Luciferase Reagent (50 μL/well) was then added and firefly luciferase luminescence was read on an Envision after a ten minute incubation. Finally, Stop and Glo reagent (50 μL/well) was added and renilla luciferase luminescence was read on an Envision after a ten minute incubation.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 547.49, ALogP 7.2, HBA 6, HBD 1, PSA 63.41, QED 0.22
Compound (SMILES): Cc1cccc(-c2c[nH]c3ncnc(N4CCOCC4)c23)c1
InChIKey: JMAPTHRNJHOVDP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13188
Assay: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 294.36, ALogP 2.77, HBA 4, HBD 1, PSA 54.04, QED 0.79
Compound (SMILES): Fc1ccc(CN[C@H]2CC[C@@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: DRVCINFCPHBBNF-FZNQNYSPSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 364.43, ALogP 3.56, HBA 5, HBD 2, PSA 70.9, QED 0.58
Compound (SMILES): FCCn1cc(-c2cc3c(cn2)cnn3-c2cccc(N3CCCNCC3)n2)cn1
InChIKey: IWDUWWSSLHPWJZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: In Vitro Cell Proliferation Potency Assay: BaF3, a murine interleukin-3 dependent pro-B cell line, parental cells, BaF3 PIM1 cells, BaF3 PIM2 cells, and MM1.S (multiple myeloma) cells were seeded at 2 k/well, 5 k/well, 5 k/well, and 10 k/well respectively, in a 384-well plate, at 45 μL/well. Test compound was added at 5 μL/well. BaF3 cells (parental and transfected) were incubated overnight, while MM1.S cells were incubated for 72 hours at 37° C., 5% CO2. CELL TITER GLO® Reagent (Promega) was added at 50 μL/well, the plates were incubated for 30 minutes, and their luminescence read on an HT Analyst.
Measurement: IC50 = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 406.47, ALogP 2.45, HBA 8, HBD 1, PSA 76.69, QED 0.55
Compound (SMILES): NC[C@](O)(c1ccc(Cl)cc1)c1ccc(-c2cn[nH]c2)cc1
InChIKey: IIRWNGPLJQXWFJ-QGZVFWFLSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) expressed in baculosomes containing NADPH reductase by fluorescence based Pan-Vera VividC450 assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 313.79, ALogP 2.92, HBA 3, HBD 3, PSA 74.93, QED 0.69
Compound (SMILES): N#CCN(CC1CC1)C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: KKOVNDIQZVPQQY-WKILWMFISA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 363.47, ALogP 3.11, HBA 6, HBD 1, PSA 85.9, QED 0.68
Compound (SMILES): COC[C@@H](O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCCN)c3)nc2c1.Cl
InChIKey: WEOKVCDNGWOSTF-BOXHHOBZSA-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 presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 492.58, ALogP 3, HBA 10, HBD 2, PSA 120.78, QED 0.31
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(F)(F)(F)(F)F)cc3)c(N)c2c1C
InChIKey: PSCQDXGBEMJRFR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 438.45, ALogP 5.48, HBA 5, HBD 2, PSA 80.9, QED 0.53
Compound (SMILES): COc1ccc2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2c1
InChIKey: XIQPDIUHKIOZOL-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Radioligand Binding Assay: Protocol 1: The assay was conducted following the literature reference Meyer E. M., et al., Analysis of 3-(4-Hydroxy, 2-Methoxybenzylidene) Anabaseine Selectivity and Activity at Human and Rat Alpha-7 Nicotinic Receptors, J. Pharmacol. Exp. Ther., 287: 918-925, 1998. The assay was conducted using the following materials: receptor source: rat brain, radioligand: [125I] α-Bungarotoxin (2200 Ci/mmol) with a final concentration of 1 nM, non-specific determinant: Methyllycaconitine (MLA) [1 μM], reference compound: Methyllycaconitine (MLA), and positive control: Methyllycaconitine (MLA). Incubation Conditions: Reactions were carried out in 20 mM HEPES (pH 7.4) containing 120 mM NaCl, 5 mM KCl, 2.5 mM CaCl2 and 1.2 mM MgSO4 at 37° C. for 90 minutes. The reaction was terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters was determined by liquid scintillation counting and compared to control values in order to ascertain any interactions of test compound with the nicotinic, ganglionic binding site.
Measurement: IC50 = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): O=C(C1CCS(=O)(=O)C1)N1CC[C@](c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: QABINSUJKJJFAK-FXMQYSIJSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin) expressed in human HepG2 cells
Measurement: EC50 > 13000 nM (pChEMBL 4.886000156402588)
Descriptors: MW 619.55, ALogP 4.45, HBA 5, HBD 0, PSA 88.59, QED 0.36
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3cc(C(F)(F)F)ccn23)n1
InChIKey: AQHOUJHKKKWAJK-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 829.85, ALogP 8.32, HBA 10, HBD 2, PSA 103.16, QED 0.12
Compound (SMILES): CC(C(=O)NC1COc2ncccc21)c1ccc(Cl)cc1Cl
InChIKey: WJPNUTYLRJIVMN-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 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 337.21, ALogP 3.74, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): COc1cc(OC)cc(N(CC2CCCO2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GBXSGEIAMQTWMD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (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 445.52, ALogP 4.36, HBA 8, HBD 0, PSA 74.53, QED 0.42
Compound (SMILES): COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)c5c(F)cccc5F)c4F)c3c2)cn1
InChIKey: PJUYURNAWZJXJZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.49, ALogP 4.62, HBA 7, HBD 2, PSA 126.93, QED 0.22
Compound (SMILES): COc1cc(CCCN2CCCCC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: FYHZHHDXFRDVFJ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 703.79, ALogP 8.17, HBA 9, HBD 2, PSA 105.91, QED 0.13
Compound (SMILES): Cc1n[nH]c2c1C(c1ccc(F)c(F)c1)c1c(C)n[nH]c1O2
InChIKey: JKOZOBNKGCZYHT-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of N-terminal 6xHis-tagged human TDO expressed in Escherichia cli Rosetta (DE3) pLysS using L-tryptophan as substrate preincubated for 1 hr measured after 15 mins in presence of bovine liver and methylene blue by spectrophotometric analysis
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 302.28, ALogP 3.31, HBA 3, HBD 2, PSA 66.59, QED 0.57
Compound (SMILES): CC(C)c1c2cc(-c3ccnc(N[C@H]4CC[C@H](NC5CCOCC5)CC4)n3)ccc2nn1C
InChIKey: LHIUZPIDLZYPRL-MXVIHJGJSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 448.62, ALogP 4.65, HBA 7, HBD 2, PSA 76.89, QED 0.57
Compound (SMILES): COc1ccn2c(-c3ccnc(Nc4ccc(N5CCC(N6CCCCC6)CC5)cc4OC)n3)c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc2c1
InChIKey: ZIDYMRBSAWLZLI-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 774.87, ALogP 8.21, HBA 11, HBD 2, PSA 118.38, QED 0.13
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCCC[C@H]2C(=O)N1
InChIKey: ZDTMGSSRQLKYTK-UGSOOPFHSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 520.39, ALogP 4.56, HBA 7, HBD 2, PSA 88.61, QED 0.46
Compound (SMILES): CC(C)C[C@H](NC(=O)C(=O)Nc1cccc2ccccc12)C(=O)N[C@@H](CC(=O)O)C(=O)O
InChIKey: SGVNFLQYMIJSSK-IRXDYDNUSA-N
Target: Caspase-1 (SINGLE PROTEIN), Mus musculus
UniProt: P29452
Assay: Inhibition of mouse recombinant ICE pre-incubated for 30 mins before Acetyl-Tyr-Val-Ala-Asp-amino-4-methylcoumarin substrate addition measured 1 hr after substrate addition by fluorescence based assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 443.46, ALogP 1.35, HBA 5, HBD 5, PSA 161.9, QED 0.37
Compound (SMILES): COc1cc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)(C)C)ccn1
InChIKey: XOPXTKOQXWMGEF-NRFANRHFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.54, ALogP 3.79, HBA 7, HBD 0, PSA 77.32, QED 0.63
Compound (SMILES): Cc1cnc(Nc2ccc(N3CCOCC3)cc2)nc1-c1cc2c(o1)CCN(S(C)(=O)=O)C2
InChIKey: YDZHOVOPBMIATL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Mus musculus
UniProt: Q62137
Assay: Inhibition of JAK3 in mouse HT2 cells assessed as suppression of cell growth
Measurement: IC50 = 848 nM (pChEMBL 6.070000171661377)
Descriptors: MW 469.57, ALogP 2.94, HBA 8, HBD 1, PSA 100.8, QED 0.61
Compound (SMILES): CC1(C)CC2=NNC(=O)c3cccc4c3c2c(n4CC2CO2)C1
InChIKey: CHUANYXVPMSWFM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Enzymatic Assay: PARP-1 enzymatic assay was conducted using a method modified from HT F Homogeneous PARP Inhibition Assay Kit (Trevigen). 8.8 nM PARP-1 was pre-incubated with different concentrations of compounds in a buffer containing 100 mM Tris-HCl pH 8.0, 100 mM NaCl, 20 mM MgCl2, and 1% DMSO for 30 min at RT. The auto-PARylation reaction was initiated by addition of 500 nM NAD and 20 ng/ul activated DNA (Sigma) and incubated at RT for 40 min. The remaining NAD was detected by incubation with cycling assay solution containing 1% ethanol, 0.30 U/ml alcohol dehydrogenase, 25 uM resazurin, and 0.25 U/ml diaphorase for 50 min at RT. The concentration of NAD is proportional to the fluorescence signal at Ex540 nm/Em 590 nm. The IC50s were calculated based on residual enzyme activity (the rate of NAD decrease) in presence of increasing concentrations of compounds.
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 309.37, ALogP 2.46, HBA 4, HBD 1, PSA 58.92, QED 0.87