lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O[C@@H](CN[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)c1ccccc1
InChIKey: RJVYQTHPYZENAN-BQFCYCMXSA-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 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 376.46, ALogP 2.96, HBA 6, HBD 3, PSA 91.13, QED 0.5
Compound (SMILES): COc1nc2ccc(C(C)(O)c3cnnn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
InChIKey: KCEVZBCVYHCXBO-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: 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 1× 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 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 476.89, ALogP 4.89, HBA 6, HBD 1, PSA 73.06, QED 0.44
Compound (SMILES): Cc1oc2c(c1CC(=O)Nc1nc(-c3ccc(C(F)(F)F)c(F)c3F)cs1)c(=O)n(C)c(=O)n2C
InChIKey: MQPVCEGYFVTWDL-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 = 8920 nM (pChEMBL 5.050000190734863)
Descriptors: MW 514.43, ALogP 3.74, HBA 8, HBD 1, PSA 99.13, QED 0.42
Compound (SMILES): Cc1cc(Nc2nccc(Oc3ccc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(OCCN5CCOCC5)c4)c4ccccc34)n2)cc2cn[nH]c12
InChIKey: QJIXTISVQSBZTF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 > 13300 nM (pChEMBL 4.875999927520752)
Descriptors: MW 752.88, ALogP 8.19, HBA 11, HBD 4, PSA 156.37, QED 0.1
Compound (SMILES): Cl.O=C1c2ccc(Cl)cc2CC1CCN1CCc2ccccc2C1
InChIKey: CDKCTEJHUVKKNR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor by liquid scintillation counting method
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 325.84, ALogP 4.14, HBA 2, HBD 0, PSA 20.31, QED 0.84
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4c(C)nn(C)c4C)nc3c2)c1
InChIKey: WCHAWRNEALMUFZ-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 447.54, ALogP 4.18, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)Cl)cc1)c1cnc(N2C[C@H](O)[C@@H](O)C2)c(-c2cncnc2)c1
InChIKey: INMCQZXOLSELDJ-ROUUACIJSA-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 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 477.86, ALogP 2.5, HBA 8, HBD 3, PSA 120.7, QED 0.46
Compound (SMILES): CC[C@H](C)N(Cc1nc2c(c(=O)[nH]1)COCC2)C(=O)CN1CCC(C(=O)c2ccc(F)cc2)CC1
InChIKey: QSAWMHWYVIPNBM-KRWDZBQOSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
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 μL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 μM, 20 nM of purified enzyme, and 250 μM of β-NAD+ in the 1× Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 μL of 5× quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 μL of the 5× quenching solution per well was added prior to the addition of β-NAD+.
Measurement: IC50 > 19000 nM (pChEMBL 4.7210001945495605)
Descriptors: MW 484.57, ALogP 2.7, HBA 6, HBD 1, PSA 95.6, QED 0.58
Compound (SMILES): CN(C)c1ccc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)cc1C#N
InChIKey: GCCGLVIEPMZLEX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 < 10 nM (pChEMBL 8)
Descriptors: MW 534.63, ALogP 2.99, HBA 9, HBD 1, PSA 133.76, QED 0.4
Compound (SMILES): COc1cc(N2CCN(S(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: NLPVVRIYZYTTIS-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 < 1000 nM (pChEMBL 6)
Descriptors: MW 724.79, ALogP 6.13, HBA 10, HBD 2, PSA 134.06, QED 0.18
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccn[nH]3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: MVRRILMCOGDYKT-UHFFFAOYSA-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 462.52, ALogP 3.77, HBA 8, HBD 2, PSA 120.3, QED 0.41
Compound (SMILES): CCCCc1cc(N2CCN(CCc3ccc(OCCCN4CCCCCC4)cc3)CC2)c2nc(CCC(=O)O)ccc2c1
InChIKey: JQNSYTMOXNMQTB-UHFFFAOYSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity at adrenergic alpha1B receptor (unknown origin) expressed in Rat1 cells assessed as inhibition of phenylephrine-induced Ca2+ flux preincubated for 30 mins followed by phenylephrine addition by Fluo-4-AM-dye based FLIPR assay
Measurement: Ki = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 600.85, ALogP 6.6, HBA 6, HBD 1, PSA 69.14, QED 0.2
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](C)N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AHWOGVXLWKIELS-OAHLLOKOSA-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 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: JDDJMJIAWGNUGT-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 405.46, ALogP 3.56, HBA 7, HBD 2, PSA 96.39, QED 0.46
Compound (SMILES): O=S(=O)(NCC1CC1)c1ccc(Nc2ccccc2)cc1C(F)(F)F
InChIKey: FSNZQFMQPKGZOB-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
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 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 370.4, ALogP 4.14, HBA 3, HBD 2, PSA 58.2, QED 0.8
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C3(C(=O)O)CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: RFKOYFYQZZFWKX-ADXZGYQBSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of human kallikrein1 at 37 degC by chromogenic substrate assay
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 611.67, ALogP 5.86, HBA 7, HBD 4, PSA 146.88, QED 0.22
Compound (SMILES): Cc1c(C)c2c(c(C)c1O)CC(CN1CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC1)C(C)O2
InChIKey: SCUZVSHLJVHGDP-UHFFFAOYSA-N
Target: Caspase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P49662
Assay: Inhibition of human recombinant N-terminal His-tagged DTT-activated caspase-4 expressed in Escherichia coli using Ac-LEVD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: Ki = 248 nM (pChEMBL 6.610000133514404)
Descriptors: MW 520.72, ALogP 4.07, HBA 8, HBD 1, PSA 68.2, QED 0.63
Compound (SMILES): CCCCOC(=O)c1cnc(N2CCN(c3nnc(-c4ccc(F)c(C#N)c4)c(C)c3C)CC2)cc1C(F)(F)F
InChIKey: NHOHZWDIZNEPTA-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 556.56, ALogP 5.47, HBA 8, HBD 0, PSA 95.24, QED 0.21
Compound (SMILES): OC1CCCCCCCNc2ncc3c(-c4ccccn4)cn(c3n2)CCCC1
InChIKey: NGJAXUZGEAUCFH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of Axl (unknown origin) by microfluidic capillary electrophoresis assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 393.54, ALogP 4.79, HBA 6, HBD 2, PSA 75.86, QED 0.62
Compound (SMILES): COc1cc(CCN2CCCCC2)c(F)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: LZLZAMJAYXYMOK-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 677.73, ALogP 7.91, HBA 8, HBD 2, PSA 96.68, QED 0.15
Compound (SMILES): O=C(c1cccc2ccccc12)c1csc2ccccc12
InChIKey: ZDPDDZLEKZATLZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cell membranes incubated for 1.5 hrs
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 288.37, ALogP 5.29, HBA 2, HBD 0, PSA 17.07, QED 0.46
Compound (SMILES): FC(F)(F)c1cc(CN2CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC2)cc(C(F)(F)F)c1
InChIKey: TWGFWBPIHYEITI-UHFFFAOYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Inhibition of human recombinant DTT-activated caspase-5 expressed in Escherichia coli using Ac-WEHD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 528.54, ALogP 5.04, HBA 6, HBD 0, PSA 38.74, QED 0.51
Compound (SMILES): Oc1ccc(-c2ccc3c(/C=C/c4ccccc4)n[nH]c3c2)cc1OCc1ccccc1
InChIKey: XNXRPRVBGWBMQP-RVDMUPIBSA-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 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 418.5, ALogP 6.68, HBA 3, HBD 2, PSA 58.14, QED 0.32
Compound (SMILES): COCC[C@@H]1C[C@H]1c1cncc(N2CCCNCC2)c1
InChIKey: FTYHMMVUGBYQCJ-CZUORRHYSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Displacement of [3H]epibatidine from rat alpha3beta4 nAChR by liquid scintillation counting
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 275.4, ALogP 2.02, HBA 4, HBD 1, PSA 37.39, QED 0.89
Compound (SMILES): COc1cc(-c2ncn(/C=C\C(=O)OC(C)C)n2)cc(C(F)(F)F)c1
InChIKey: NLNGWFLRRRYNIL-PLNGDYQASA-N
Target: Exportin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14980
Assay: Inhibition of XPO1 in human HPBALL cells
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 355.32, ALogP 3.39, HBA 6, HBD 0, PSA 66.24, QED 0.61
Compound (SMILES): CC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(C(C)(C)C)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN(CC)CC)C(=O)N[C@@H](CO)C(=O)OC
InChIKey: YUNDLGQJZQUDNB-LTLCPEALSA-N
Target: Chromodomain Y-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N8U2
Assay: Antagonist activity at recombinant human C-terminal His-tagged CDYL2 chromodomain (1 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 809.06, ALogP 3.4, HBA 9, HBD 6, PSA 195.27, QED 0.07
Compound (SMILES): CN(C)S(=O)(=O)Nc1ccc(Oc2ccccc2)c(-c2cn(C)c(=O)c3[nH]ccc23)c1
InChIKey: PCDHNCIAXVZAIK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human N-terminal His6-tagged BRD4 BD1-BD2 (K57 to K550 residues) after 1 hr using alexa-647 conjugated probe by TR-FRET assay
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 438.51, ALogP 3.54, HBA 5, HBD 2, PSA 96.43, QED 0.48
Compound (SMILES): Nc1onc(-c2ccc(Br)cc2)c1C(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: QLUSYRMWCOICRS-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 assessed as reduction in CO2 hydration preincubated for 15 mins by stopped flow assay
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 437.28, ALogP 2.59, HBA 6, HBD 3, PSA 141.31, QED 0.57
Compound (SMILES): CC1c2ncn(-c3cnccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: MGIXWTWNCJHXKS-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321 N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250Ã¿ the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate. Cells were incubateÂ  with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 uL/well of BzATP (final concentration is 250 uM BzATP (human and rat) or 600 (mouse)). The fluorescence change was measured 180 seconds after adding the agonist.
Measurement: IC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 421.81, ALogP 4.09, HBA 5, HBD 0, PSA 63.91, QED 0.62
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)[nH]c3cnc4ccc(-c5ccc(OCCCN(C)C)nc5)cc4c32)C1
InChIKey: JDAPKZUDSPQCGU-KDURUIRLSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Cellular Assay: Assay d) MDA-MB-468 cells (human breast adenocarcinoma ##ATCC HTB 132) were seeded at 1500 cells/well in 40 μl of DMEM containing 10% FBS and 1% glutamine into Greiner 384 well black flat-bottomed plates. Cell plates were incubated for 18 h in a 37° C. incubator before dosing with compounds of formula (I) in 100% DMSO using acoustic dispensing. Compounds were dosed in a 12 point concentration range into a randomised plate map. Control wells were generated either by dosing of 100% DMSO (max signal) or addition of a reference compound (a PI3K-β inhibitor) that completely eliminated the pAKT signal (min control). Plates were incubated, at 37° C. for 2 h, cells were then fixed by the addition of 10 μl of a 3.7% formaldehyde solution. After 30 minutes the plates were washed with PBS using a Tecan PW384 plate washer. Wells were blocked and cells permeabilised with the addition of 40 μl of PBS containing 0.5% Tween20 and 1% Marvel™ (dried milk powder) and incubated for 60 minutes at r.t. The plates were washed with PBS containing 0.5% (v/v) Tween20 and 20 μl rabbit anti-phospho AKT Ser473 (Cell Signalling Technologies, #3787) in same PBS-Tween+1% Marvel™ was added and incubated overnight at 4° C. Plates were washed 3 times with PBS 0.05% Tween 20 using a Tecan PW384. 20 μl of secondary antibody Alexa Fluor 488 anti-Rabbit (Molecular Probes, #A11008) diluted in PBS+0.05% Tween20 containing 1% Marvel™ was added to each well and incubated for 1 h at r.t. Plates were washed three times as before then 20 μl PBS added to each well and plates sealed with a black plate sealer. The plates were read on an Acumen plate reader as soon as possible, measuring green fluorescence after excitation with 488 nm laser.
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 447.54, ALogP 3.62, HBA 7, HBD 1, PSA 85.27, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: NAFMCDLLMRKVNJ-GOSISDBHSA-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 469.55, ALogP 4.02, HBA 8, HBD 1, PSA 103.19, QED 0.41
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)n(C)c3cnc4cc(F)c(-c5ccc(OCCCN(C)C)nc5F)cc4c32)C1
InChIKey: GCCDCEIIJOUYDQ-IYBDPMFKSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Cellular Assay: Assay d) MDA-MB-468 cells (human breast adenocarcinoma ##ATCC HTB 132) were seeded at 1500 cells/well in 40 μl of DMEM containing 10% FBS and 1% glutamine into Greiner 384 well black flat-bottomed plates. Cell plates were incubated for 18 h in a 37° C. incubator before dosing with compounds of formula (I) in 100% DMSO using acoustic dispensing. Compounds were dosed in a 12 point concentration range into a randomised plate map. Control wells were generated either by dosing of 100% DMSO (max signal) or addition of a reference compound (a PI3K-β inhibitor) that completely eliminated the pAKT signal (min control). Plates were incubated, at 37° C. for 2 h, cells were then fixed by the addition of 10 μl of a 3.7% formaldehyde solution. After 30 minutes the plates were washed with PBS using a Tecan PW384 plate washer. Wells were blocked and cells permeabilised with the addition of 40 μl of PBS containing 0.5% Tween20 and 1% Marvel™ (dried milk powder) and incubated for 60 minutes at r.t. The plates were washed with PBS containing 0.5% (v/v) Tween20 and 20 μl rabbit anti-phospho AKT Ser473 (Cell Signalling Technologies, #3787) in same PBS-Tween+1% Marvel™ was added and incubated overnight at 4° C. Plates were washed 3 times with PBS 0.05% Tween 20 using a Tecan PW384. 20 μl of secondary antibody Alexa Fluor 488 anti-Rabbit (Molecular Probes, #A11008) diluted in PBS+0.05% Tween20 containing 1% Marvel™ was added to each well and incubated for 1 h at r.t. Plates were washed three times as before then 20 μl PBS added to each well and plates sealed with a black plate sealer. The plates were read on an Acumen plate reader as soon as possible, measuring green fluorescence after excitation with 488 nm laser.
Measurement: IC50 = 13700 nM (pChEMBL 4.860000133514404)
Descriptors: MW 497.55, ALogP 3.91, HBA 8, HBD 0, PSA 74.41, QED 0.27
Compound (SMILES): CC(c1ccccc1)c1ccc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
InChIKey: BSXBVSWEULDBKN-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 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 367.45, ALogP 4.67, HBA 2, HBD 2, PSA 57.78, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C[Si](C)(C)C)c4)nc3c2)c1
InChIKey: VVKVBFYAFWGFSV-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 487.68
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(C#N)ccc3C#N)CC2)C1
InChIKey: JOGNOKZDYQQWGP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 533.57, ALogP 3.54, HBA 8, HBD 1, PSA 141.42, QED 0.41
Compound (SMILES): CCN1CCC[C@H]1c1noc(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)n1
InChIKey: QYJJHEKFWCNKKZ-IBGZPJMESA-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 515.4, ALogP 5.81, HBA 9, HBD 1, PSA 98.43, QED 0.31
Compound (SMILES): COc1ccc(CCNc2nc(N)c3nc(-c4ccco4)sc3n2)cc1OC
InChIKey: MRNAGDNRGKXOJA-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Inverse agonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 397.46, ALogP 3.6, HBA 9, HBD 2, PSA 108.32, QED 0.49
Compound (SMILES): CC(C)c1cc(NC(=O)Nc2ccc(Oc3ccnc(Nc4ccc5c(c4)NC(=O)C5)n3)c3ccccc23)n(-c2ccc(OCCN3CCOCC3)cc2)n1
InChIKey: QGEZMNVGCVUCMW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 1540 nM (pChEMBL 5.809999942779541)
Descriptors: MW 739.84, ALogP 7.32, HBA 11, HBD 4, PSA 156.79, QED 0.1
Compound (SMILES): CCCN1CC[C@H]2CC(=O)[C@H](Cc3ccc(OC)cc3)[C@H]3CCC[C@@H]1[C@H]23
InChIKey: RRRGKFRGFXTFPJ-DPCCUFRHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DADLE from human DOR expressed in HEK cells measured after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 355.52, ALogP 4.34, HBA 3, HBD 0, PSA 29.54, QED 0.79
Compound (SMILES): CCS(=O)(=O)Nc1ccc(Oc2ccccc2)c(-c2cn(C)c(=O)c3[nH]ccc23)c1
InChIKey: JEPTWXASUVPZQH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human N-terminal His6-tagged BRD4 BD1-BD2 (K57 to K550 residues) after 1 hr using alexa-647 conjugated probe by TR-FRET assay
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 423.49, ALogP 4.09, HBA 5, HBD 2, PSA 93.19, QED 0.49
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3c(F)cccn23)n1
InChIKey: WTYLEWGEAKNPLB-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 811.89, ALogP 6.43, HBA 11, HBD 2, PSA 137.3, QED 0.16
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: ABHYRAOZUATJPX-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human 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 492.51, ALogP 4.58, HBA 8, HBD 2, PSA 111.85, QED 0.37
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(NC4CCC(C(=O)NO)CC4)ccc3OCC)nc12
InChIKey: UIPYYBRFOQOGSC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human N-terminal GST tagged HDAC6 expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate after 30 mins by fluorescence analysis
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 468.56, ALogP 3.15, HBA 8, HBD 4, PSA 134.16, QED 0.29
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(S(=O)(=O)N4CCN(CCC(=O)NO)CC4)ccc3OCC)nc12
InChIKey: WQAWXCMACOECMF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human N-terminal GST tagged HDAC6 expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate after 30 mins by fluorescence analysis
Measurement: IC50 = 2360 nM (pChEMBL 5.630000114440918)
Descriptors: MW 547.64, ALogP 0.88, HBA 10, HBD 3, PSA 162.75, QED 0.25
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(C(F)(F)F)c(F)c3)CC2)C1
InChIKey: AJXWDVYAVCKCDI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 552.54, ALogP 4.21, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): COc1cc(C2CCN(C3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VMVAXVQCRBDHOB-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 760.86, ALogP 8.35, HBA 9, HBD 2, PSA 99.92, QED 0.14
Compound (SMILES): N#CCC(=O)N1CCCC(c2ncn3cnc4[nH]ccc4c23)C1
InChIKey: RVHXGUCJVOYTRJ-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 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 308.35, ALogP 1.83, HBA 5, HBD 1, PSA 90.08, QED 0.78
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(CCCC#N)CCO1
InChIKey: CFLVHNKVJHQBJP-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 7.301000118255615)
Descriptors: MW 502.4, ALogP 5.07, HBA 8, HBD 1, PSA 92.53, QED 0.41
Compound (SMILES): N#CC(C#N)=C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: PMRKEYOSDJGKFC-AULYBMBSSA-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 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 317.36, ALogP 2.85, HBA 6, HBD 1, PSA 106.45, QED 0.73
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccccc1)C(=O)NCCCCC[N+](C)(C)C
InChIKey: FCUVIHIUNUOUJE-FMYROPPKSA-O
Target: Chromodomain Y-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N8U2
Assay: Antagonist activity at recombinant human C-terminal His-tagged CDYL2 chromodomain (1 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 580.79, ALogP 3.06, HBA 4, HBD 4, PSA 116.4, QED 0.17
Compound (SMILES): Cc1ccccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: BSVJKUPXZKILRQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 495.59, ALogP 3.75, HBA 7, HBD 2, PSA 118.76, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: JBBAETKDVUXXJY-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 821.95, ALogP 6.37, HBA 12, HBD 2, PSA 137.3, QED 0.14
Compound (SMILES): Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2nc(C#N)c(Oc3ccc(F)cc3)c(Cl)c2c1
InChIKey: FEMFLJUOZBWZNG-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 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 519.36, ALogP 6.36, HBA 6, HBD 1, PSA 83.96, QED 0.29
Compound (SMILES): COc1ccc(C(=O)n2c(C3CCC3)nc3ccccc32)cc1
InChIKey: IDDHPLVFJHQUOF-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cell membranes incubated for 1.5 hrs
Measurement: Ki = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 306.37, ALogP 4, HBA 4, HBD 0, PSA 44.12, QED 0.73
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MLUFVERLBQGOEV-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 419.49, ALogP 3.57, HBA 8, HBD 1, PSA 85.53, QED 0.47
Compound (SMILES): COc1ccc(C(=O)n2c(C(C)(C)C)nc3ccccc32)cc1
InChIKey: HGAVVRICQYZBRK-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cell membranes incubated for 1.5 hrs
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 308.38, ALogP 4.03, HBA 4, HBD 0, PSA 44.12, QED 0.72
Compound (SMILES): C[C@]12CC[C@H](C[C@H](N3C(=O)C(N[C@@H](CO)C(=O)O)Nc4ccccc43)C1)N2C1CCCCCCC1
InChIKey: OISHVNQWAMEVNR-UEWFJKSBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20ug membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 500uL binding buffer (5mM MgCl2, 5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 uM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 25970 nM (pChEMBL 4.590000152587891)
Descriptors: MW 484.64, ALogP 3.3, HBA 6, HBD 4, PSA 105.14, QED 0.49
Compound (SMILES): C=CC(=O)Nc1ccc(NS(=O)(=O)c2cccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)c2)cc1
InChIKey: JQBQAGHSJMBPSH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3Kbeta (P118 to S1070 residues) expressed in mammalian expression system incubated for 60 mins by ADAPTA assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 569.65, ALogP 4.81, HBA 8, HBD 3, PSA 136.63, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)no2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HGOIJUTXACYYTH-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 4.68, HBA 9, HBD 0, PSA 91.33, QED 0.35