lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(CCCCCCOc1ccc2cc1COC/C=C/COCc1cccc(c1)-c1ccnc(n1)N2)NO
InChIKey: IYBYMTCQQMFOHB-AATRIKPKSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of full length human recombinant C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in insect cells preincubated with enzyme followed by fluorogenic Arg-His-Lys-Lys(Ac)-AMC substrate addition measured after 2 hrs by fluorescence assay
Measurement: IC50 = 2170 nM (pChEMBL 5.659999847412109)
Descriptors: MW 518.61, ALogP 5.32, HBA 8, HBD 3, PSA 114.83, QED 0.16
Compound (SMILES): N#CC1(NC(=O)[C@@H]2Cc3ccc(c(Cl)c3)OCCCCOc3cc(C(F)(F)F)ccc3C(=O)N2)CC1
InChIKey: XAPRSGPLBWSEHV-IBGZPJMESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using DBF as substrate by fluorescence assay
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 521.92, ALogP 4.42, HBA 5, HBD 2, PSA 100.45, QED 0.61
Compound (SMILES): O=C(O)CCc1ccc2cc(Cc3ccccc3)cc(N3CCN(CCc4ccc(OCCCN5CCCCCC5)cc4)CC3)c2n1
InChIKey: FZTMDWIJTHPEMP-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist activity at human Histamine H1 receptor expressed in CHO cells assessed as inhibition of histamine-induced calcium flux at 100 nM preincubated for 30 mins followed by histamine addition by Fluo-4-AM dye based FLIPR assay
Measurement: Kd = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 634.87, ALogP 6.85, HBA 6, HBD 1, PSA 69.14, QED 0.15
Compound (SMILES): CCN(CC)C(=O)c1ccc2cc1CN(C)C(=O)[C@H](Nc1ccc3c(N)nccc3c1)c1ccc(c(C)c1)[C@@H](C)COC(=O)N2
InChIKey: KHVYVAAEFVFJSL-WKRVVKTRSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of alpha-thrombin (unknown origin) using pyroGlu-Pro-Arg-pNA as substrate assessed as release of pNA after 10 to 120 mins by spectrophotometric method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 608.74, ALogP 6.08, HBA 7, HBD 3, PSA 129.89, QED 0.25
Compound (SMILES): CCOc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CNCCO1
InChIKey: KHSCTMVMPMKLGB-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 449.34, ALogP 4.45, HBA 7, HBD 2, PSA 77.53, QED 0.55
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(Cl)c(F)c3)CC2)C1
InChIKey: WDOHYLSCXALEBN-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 518.98, ALogP 3.84, HBA 7, HBD 1, PSA 106.73, QED 0.43
Compound (SMILES): CCOC(=O)CN1CCN(CCCNC(=O)c2cc3nccc(Oc4ccc(NC(=O)Nc5cc(C)ccc5F)cc4)c3s2)CC1
InChIKey: CSJKWUOGGSICJS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: FLIPR (Fluorometric Imaging Plate Reader) Technology Assay: Automated FLIPR (Fluorometric Imaging Plate Reader) technology was used to screen for inhibitors of PDGF induced increases in intracellular calcium levels in fluorescent dye loaded endothelial cells. NHDF-Ad (Normal human dermal fibroblasts) (Lonza) were seeded in 384-well fibronectin coated black-walled plates overnight at 37° C./5% CO2. Cells were loaded with calcium indicator Fluo-4 for 45 minutes at 37° C. Cells were washed 4 times (ELx405-CW, Bio-Tek) to remove extracellular dye. Test compounds were reconstituted in 100% DMSO and added to the cells to give a final DMSO concentration of 0.1%. For screening, cells were pre-incubated with test agents for 30 minutes, at a single concentration (10 μM) or at concentrations ranging from 0.001 nM to 10 μM followed by PDGF stimulation (10 ng/mL). Changes in fluorescence at 515 nm were measured simultaneously in all 384 wells using a cooled CCD camera.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 648.76, ALogP 5.48, HBA 9, HBD 3, PSA 125.13, QED 0.14
Compound (SMILES): COc1cccc(-c2cccc(C3(c4ccccc4)NC(=N)N(C4CCCCC4)C3=O)c2)c1
InChIKey: GRHXGIBGTCXXSD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay : The recombinant human BACE1, Cathepsin D, and Cathepsin E enzymes were purchased from R&D Systems (catalog numbers are 931-AS, 1014AS and 1294AS, respectively). The enzymatic inhibition activity assays were determined using the fluorescence resonance energy transfer (FRET) assay. The assays were performed in a 384-well plate format. The recombinant human BACE-1 enzyme (R&D Systems, catalog#931-AS) was diluted to 20 ng/μL in assay buffer (100 mM sodium acetate pH 4.0), 10 point 1:3 serial dilutions of compound in DMSO were preincubated with the enzyme for 15 min at room temperature. The concentration of Cathepsin D was 20 ng/μL, and 1 ng/μL of Cathepsin E was used. CatD and CatE were activated by incubation in assay buffer (0.1 M NaOAc, 0.2 M NaCl, pH 3.5) at room temperature for 30 min. Subsequently, the rhBACE-1 substrate (R&D Systems, catalog# ES004), the Cathepsin D and Cathepsin E substrate (R&D Systems, Catalog # ES001) were added accordingly to final concentration
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 439.56, ALogP 5.31, HBA 3, HBD 2, PSA 65.42, QED 0.57
Compound (SMILES): Nc1onc(-c2ccc(Cl)cc2Cl)c1C(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: ZOSFXUWRABBACM-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 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 427.27, ALogP 3.13, HBA 6, HBD 3, PSA 141.31, QED 0.58
Compound (SMILES): CC(C)C(CS(=O)(=O)c1ccc(-c2cccc(CNC(=O)c3nc4ccccc4c(=O)[nH]3)c2)cc1)N(O)C(N)=O
InChIKey: VKESMHHXVWGWQQ-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human AMPA-activated MMP8 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 563.64, ALogP 3.09, HBA 7, HBD 4, PSA 175.55, QED 0.18
Compound (SMILES): C[C@H]1C[C@H]2CSC(N)=N[C@@]2(c2nc(NC(=O)c3ccc(C(F)(F)F)cn3)cs2)CO1
InChIKey: ZZHRZUNUORUAKI-NSTVUXKKSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2 using biotin-GLTNIKTEEISEISYEVEFR-C[Oregon green]KK-OH as substrate after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 457.5, ALogP 3.49, HBA 8, HBD 2, PSA 102.49, QED 0.73
Compound (SMILES): COc1cc(N2CCC(N3CCC(C)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: KUYIQVZTFYAICK-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 728.85, ALogP 8.44, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@H]2Cc2cccc(-n3nccn3)c2)c1
InChIKey: PQIZGRDRKSOBSA-IBGZPJMESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: OX Inhibition Assay: Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 ug/mL G418, 100 U/mL penicillin, 100 ug/mL streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37 C. in 5% CO2.Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH: water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/L and 20 mM HEPES for use in the assay at a final concentration of 3 nM.Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/L and 20 mM HEPES.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 413.49, ALogP 3, HBA 7, HBD 0, PSA 81.73, QED 0.5
Compound (SMILES): C[C@H](NC(=O)C(=O)NC1CCCCC1)C(=O)N[C@@H](CC(=O)O)C(=O)COC(=O)c1c(Cl)cccc1Cl
InChIKey: VMCLZBMIORMDHX-LRDDRELGSA-N
Target: Caspase-8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14790
Assay: Inhibition of recombinant MCH5 (unknown origin) pre-incubated for 60 mins with Acetyl-Tyr-Val-Ala-Asp-amino-4-methylcoumarin substrate followed by enzyme addition by fluorescence based assay
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 544.39, ALogP 1.63, HBA 7, HBD 4, PSA 167.97, QED 0.25
Compound (SMILES): Cc1cccnc1C#Cc1c(N)ncnc1N[C@@H](C)c1nc2cccc(Cl)c2c(=O)n1-c1ccccc1
InChIKey: WCMVTMHOLKEVJB-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2xKm ATP (100-300 uM), 10 uM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 1% (v/v) DMSO at the following concentrations for each isoform: PI3K alpha, beta, delta, and gamma at 50 picomolar (pM) and PI3Kgamma at 2 nanomolar (nM). After an assay reaction time of 30 minutes at 25° C., reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIP3, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 us delay and 500 us read window).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 507.99, ALogP 4.69, HBA 8, HBD 2, PSA 111.61, QED 0.34
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2c(F)ccc(Cl)c2c(=O)n1-c1cncc(F)c1
InChIKey: DHEKIAITWHNQAM-QMMMGPOBSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length PI3K p110alpha/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 469.84, ALogP 2.71, HBA 10, HBD 3, PSA 161.42, QED 0.41
Compound (SMILES): Cc1cc(S(=O)(=O)[C@@]2(c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)CCN(C(=O)[C@H]3CC[C@H](C(=O)O)CC3)C2)ccc1F
InChIKey: FOMZHKMHJLHIQZ-RPPIVITFSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at LXRalpha (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 641.58, ALogP 6.22, HBA 4, HBD 1, PSA 91.75, QED 0.3
Compound (SMILES): N#CC1=C(N)OC2=C(C(=O)CCC2)C1c1ccc(-c2nnn[nH]2)cc1
InChIKey: LMQLKVZHTLWWKA-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 expressed in Escherichia coli assessed as reduction in CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by stopped-flow assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 334.34, ALogP 1.68, HBA 7, HBD 2, PSA 130.57, QED 0.85
Compound (SMILES): Nc1nc(NCCc2cccc(O)c2)nc2sc(-c3ccco3)nc12
InChIKey: BPJQHNKRHLCRCJ-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 353.41, ALogP 3.29, HBA 8, HBD 3, PSA 110.09, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(OCc2cn(-c3ccccc3)nn2)cc1
InChIKey: SAASQQDVQJBKBR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 pre-incubated for 15 mins by stopped flow carbon dioxide hydrase assay
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 330.37, ALogP 1.49, HBA 6, HBD 1, PSA 100.1, QED 0.76
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(Cl)cc3)C2)CC1
InChIKey: OWEBVLUQSSGDRX-UAVUOLJFSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at LXRalpha (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 644, ALogP 6.42, HBA 4, HBD 1, PSA 91.75, QED 0.37
Compound (SMILES): CN(C)C/C=C/C(=O)N1CCC(n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: KAKJQMPMDALLHT-RMKNXTFCSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 497.6, ALogP 4.15, HBA 8, HBD 1, PSA 102.4, QED 0.38
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)nn21
InChIKey: TZAAHFAAEVJUJO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 479.54, ALogP 4.97, HBA 6, HBD 3, PSA 111.27, QED 0.32
Compound (SMILES): COc1ccc(C[C@H]2C(=O)C[C@@H]3CCN(CCC(C)C)[C@@H]4CCC[C@H]2[C@@H]34)cc1
InChIKey: NOXURLMMPFLQQR-ANYFMGCHSA-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 383.58, ALogP 4.98, HBA 3, HBD 0, PSA 29.54, QED 0.69
Compound (SMILES): c1cc2c(ncn3nnc(C4CCCCCC4)c23)[nH]1
InChIKey: QCVMWZJIMQPVCO-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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 255.32, ALogP 3.04, HBA 4, HBD 1, PSA 58.87, QED 0.68
Compound (SMILES): N#C/C(=C\N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1)c1ccc(Cl)cc1
InChIKey: OIZPIQJMCWMTLP-FOWTUZBSSA-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 403.88, ALogP 4, HBA 6, HBD 1, PSA 85.9, QED 0.52
Compound (SMILES): O=C(O)c1ccc2cccc(N3CCN(CCc4ccc(OCCCN5CCCCCC5)cc4)CC3)c2n1
InChIKey: VGLVSBTUAYHUEF-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 > 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 516.69, ALogP 4.94, HBA 6, HBD 1, PSA 69.14, QED 0.38
Compound (SMILES): OC(CNC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)(c1ccccc1)C(F)(F)F
InChIKey: PPWMFRBJDTVYQO-STFKQGPRSA-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 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 458.49, ALogP 3.92, HBA 6, HBD 3, PSA 91.13, QED 0.41
Compound (SMILES): Cc1c(-c2c(Cl)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2sccn2c1=O
InChIKey: VUSIZNYCXFPUFG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Tyrosine Kinase Assay: The assays were performed in V-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerolphosphate, 0.015% Brij 35 surfactant and 4 mM DTT). The reaction was initiated by the combination of Jak2 tyrosine kinase with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 minutes and terminated by adding 45 μL of 35 mM EDTA to each sample.
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 559.05, ALogP 5.1, HBA 7, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): CCCC1(C(O)c2cccc([C@H]3[C@H](O)CC(=O)[C@@H]3C/C=C\CCCC(=O)OC)c2)CCC1
InChIKey: HAOFKXXCXDQHEZ-TZTOVLLNSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Agonist activity at human recombinant TP receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 442.6, ALogP 5.01, HBA 5, HBD 2, PSA 83.83, QED 0.29
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3F)C2)n1C
InChIKey: XIHOJUYAGODVFH-VGSWGCGISA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 66.1 nM (pChEMBL 7.179999828338623)
Descriptors: MW 445.54, ALogP 4.42, HBA 7, HBD 0, PSA 59.98, QED 0.4
Compound (SMILES): CCS(=N)(=O)Cc1cc(F)cc(Nc2ncc(F)c(-c3ccc(F)cc3OC)n2)c1
InChIKey: OAAHCIALZYFQLH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: CDK2/CycE Kinase Assay: Recombinant fusion proteins of GST and human CDK2 and of GST and human CycE, expressed in insect cells (Sf9) and purified by Glutathion-Sepharose affinity chromatography, were purchased from ProQinase GmbH (Freiburg, Germany). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI Peptide Technologies (Berlin, Germany)For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK2/CycE in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 436.46, ALogP 4.88, HBA 6, HBD 2, PSA 87.96, QED 0.55
Compound (SMILES): CN(c1ccc(S(=O)(=O)NC2CC2)cn1)[C@@H]1CCN(c2ncnc3[nH]ccc23)C1
InChIKey: RJDFEVIMBGLEBT-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzymatic Assay: JAK1/2/3 kinase assay are performed in vitro using Kit-Tyr 6 Peptide (Invitrogen, Cat. No. PV4122). TYK2 kinase assay are performed in vitro using Z'-LYTE™ Kinase Assay Kit-Tyr 3 Peptide (Invitrogen, Cat. No. PV3192). Recombinant human JAK1/2/3 or TYK2 catalytic domains are from Invitrogen (Cat No. PV4774/PV4210/PV3855/PV4790); All reactions (20 μL) are started by adding 2.5 μL of the testing compound in 4% DMSO solution, 5 μL of Kinase/Peptide substrate Mixture (3.2, 0.04, 0.2 or 8 μg/mL for Recombinant human JAK1/2/3 catalytic domains, 4 μM for Z-LYTE™ Tyr 6 peptide or Z-LYTE™ Tyr 3 peptide) or Phospho-Peptide solution (Invitrogen, Cat. No. PV3192, diluted with 1.33× Kinase Buffer), 2.5 μL ATP Solution (300/100/40/100M, JAK1/JAK2/JAK3/TYK2) or 1.33× Kinase Buffer (Invitrogen, Cat. No. PV3189, 5× diluted with distilled water). The 384-well assay plate (Corning, Cat. No. 3575) is mixed and incubated at room temperature for 1 hour. 5 μL of the Development Solution (Dilute Development Reagent A (Cat. No. PV3297) is diluted to 1/64 with Development Buffer (Cat. No. PV3127) for JAK1, JAK2 and JAK3 assay; Development Reagent A (Cat. No. PV3297) is diluted to 1/2048 with Development Buffer (Cat. No. PV3127) for TYK2 assay. The diluted Development Solution is then added to each well, mixed and incubated at room temperature for another 1 hour. The kinase reaction is then stopped by adding 5 μL of the Stop Reagent (Invitrogen, Cat. No. PV3094), and the plate is read with Wallac 1420 VICTOR3 Multilabel Counter (PerkinElmer™) at 445 nm and 520 nm fluorescence. All compounds are initially tested at 8 different concentrations (1 μM down to 0.0003 μM) using a 1:3 serial dilution scheme.
Measurement: IC50 = 0.055 nM (pChEMBL 10.260000228881836)
Descriptors: MW 413.51, ALogP 1.51, HBA 7, HBD 2, PSA 107.11, QED 0.63
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C5CCN(C)CC5)c4)nc3c2)c1.Cl
InChIKey: WWJUKYMCFMIUBZ-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 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 529.69, ALogP 4.91, HBA 9, HBD 1, PSA 80.57, QED 0.31
Compound (SMILES): CCc1ccccc1-n1c(Cn2nc(-c3cn[nH]c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: RMFKLMYYMKWEOP-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 476.54, ALogP 4.02, HBA 8, HBD 2, PSA 120.3, QED 0.39
Compound (SMILES): c1ccc(-c2ccc(-c3cnc(-c4ccccc4)[nH]3)cn2)cc1
InChIKey: LXRPAWBWBSNMJX-UHFFFAOYSA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O60760
Assay: Enzyme Immunoassay (EIA)): The assay is carried out by the following steps: 1. Inhibitor screening is performed in 100 mM Tris-HCl, pH 8.0 containing 1 mM GSH, 1 mM MgCl.sub.2, 4% inhibitor/DMSO, 40 .mu.M PGH.sub.2 and 25 ng of PGDS in a total volume of 125 .mu.L. 2. A reaction mixture containing 100 mM Tris-HCl, pH 8.0, 1 mM GSH, 1 mM MgCl.sub.2, 25 ng H-PGDS and 4% inhibitor or DMSO (uninhibited reaction) is preincubated at 25.degree. C. for 10 minutes. 3. Reactions are initiated using 5 .mu.L of PGH.sub.2 and quenched every 15 seconds for one minute. Reactions are quenched by taking 10 .mu.L of reaction mixture and adding to 490 .mu.L of 100 mM phosphate buffer containing 0.1% BSA, 400 mM NaCl, 1 mM EDTA, 20 mM FeCl.sub.2, 10% 1N HCl, and 0.01% azide to prevent the non-enzymatic formation of PGD.sub.2 from PGH.sub.2. The FeCl.sub.2 serves the purpose of reducing PGH.sub.2 to 12-HHT. (Quench buffer is kept on ice at all times). 4. Quenched samples (5 .mu.L) are further diluted 100 fold in 495 .mu.L of 100 mM.
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 297.36, ALogP 4.81, HBA 2, HBD 1, PSA 41.57, QED 0.59
Compound (SMILES): O=C/C=C1\O[C@@H]2CC(=O)N2C1(C/C=C/c1ccccc1)C(=O)OCc1ccccc1
InChIKey: KBUJSCWFZMYQLR-QQKZXBOMSA-N
Target: Beta-lactamase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P00811
Assay: Cell Free Inhibition Assay: The inhibitory concentrations (IC50, [uM]) of the beta -lactamase inhibitors against purified TEM-1, SHV-1 and AmpC beta -lactamases are assessed by determining the concentration of inhibitor at which 50% of the nitrocefin hydrolysis is inhibited by the particular enzyme. Assays are performed with beta -lactamases expressed in the pET system (Novagen, San Diego, Calif.) without signal peptides. They contain an N-terminal hexa-Histidine tag that is used for purification on Ni-NTA (Qiagen, Hilden, Germany). The compounds are prepared as 50 mM stocks in DMSO and diluted into buffer P1 (50 mM phosphate, pH 7) to a final concentration of 10% DMSO. All further dilutions are done in P2 (P1 with 10% DMSO). Enzyme and compound dilutions are pre-incubated for 10 min at 37 C. and the reaction is started with the addition of pre-warmed (37 C.) nitrocefin at a final concentration of 50 mM. The change in absorption at 490 nm is followed at 37 C. for 10 min with 30 s intervals.
Measurement: IC50 = 17079.5 nM (pChEMBL 4.769999980926514)
Descriptors: MW 403.43, ALogP 3.24, HBA 5, HBD 0, PSA 72.91, QED 0.31
Compound (SMILES): FC1(F)Oc2ccc(NC[C@H]3CC[C@H](c4nnn5cnc6[nH]ccc6c45)CC3)cc2O1
InChIKey: IVYQLKRWHVUDJP-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 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 426.43, ALogP 4.31, HBA 7, HBD 2, PSA 89.36, QED 0.51
Compound (SMILES): CCCS(=O)(=O)Nc1cccc(C(=O)c2c[nH]c3ncc(-c4cnc(OC)nc4)cc23)c1F
InChIKey: QDIMNRNQAKCATG-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 469.5, ALogP 3.55, HBA 7, HBD 2, PSA 126.93, QED 0.38
Compound (SMILES): COc1ccc(CNc2nc(N3CC4CC4C3)ncc2C(=O)N[C@H]2CC[C@H](O)CC2)cc1Cl
InChIKey: NKAVILAJSNUOES-VNGAXPGBSA-N
Target: Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha (SINGLE PROTEIN), Bos taurus
UniProt: P11541
Assay: Enzyme Assay: Method: The test compound or solvent was incubated at 25° C. for 15 min with enzyme solution (0.2 μg/mL) in Tris-HCl buffer of pH 7.5. 100 μM cGMP and 0.03 μM [3H] cGMP were then added to activate the reaction. The mixture was incubated for 20 min. The reaction was stopped at 100° C. By addition of snake venom nucleotidase, the product [3H] GMP was converted into [3H] Guanosine, which was separated with AG1-X2 resin. The amount of [3H] Guanosine was measured.
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 471.99, ALogP 3.24, HBA 7, HBD 3, PSA 99.61, QED 0.57
Compound (SMILES): CCc1sc2ccccc2c1C(=O)c1cccc2ccccc12
InChIKey: VRVFAVMWSXPEJE-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 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 316.43, ALogP 5.85, HBA 2, HBD 0, PSA 17.07, QED 0.43
Compound (SMILES): C[C@H](NC(=O)CCc1nc2cccnc2n1Cc1ccc(OC(F)(F)F)cc1)c1ccc(Cl)cc1
InChIKey: HXYXHSDYBDFOFO-INIZCTEOSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human recombinant ATX/LPC 18:1-mediated mouse 4T1 cell migration after overnight incubation by Transwell assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 502.92, ALogP 5.84, HBA 5, HBD 1, PSA 69.04, QED 0.33
Compound (SMILES): COc1ccc(/C=C/C(=O)Nc2ccc(CN(C)Cc3ccccc3)cc2)cc1OC
InChIKey: SBRJGGDKKJIEFJ-FOWTUZBSSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured up to 180 secs by spectrophotometric analysis
Measurement: IC50 = 3720 nM (pChEMBL 5.429999828338623)
Descriptors: MW 416.52, ALogP 4.99, HBA 4, HBD 1, PSA 50.8, QED 0.5
Compound (SMILES): C=CC(=O)NC1CCN(S(=O)(=O)c2ccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)cc2)CC1
InChIKey: YOGHJOPHCBCAKS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta (R108 to Q1044 residues) expressed in mammalian expression system incubated for 60 mins by ADAPTA assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 561.67, ALogP 3.34, HBA 8, HBD 2, PSA 127.84, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C5CCN(S(C)(=O)=O)CC5)c4)nc3c2)c1
InChIKey: IVRYMOBVZPFZQJ-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 562.7, ALogP 4.66, HBA 9, HBD 0, PSA 102.68, QED 0.29
Compound (SMILES): CCOCc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GOURCRKPQYORGE-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 443.55, ALogP 5.12, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): COc1ccc(C(=O)Nc2onc(-c3c(Cl)cccc3Cl)c2C(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: SGCUEGUVJYPVCB-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 = 67.1 nM (pChEMBL 7.170000076293945)
Descriptors: MW 561.4, ALogP 4.81, HBA 7, HBD 3, PSA 153.62, QED 0.29
Compound (SMILES): CCCCCC(O)c1ccc([C@H]2CCC(=O)[C@@H]2C/C=C\CCCC(=O)OC)cc1
InChIKey: OHMVJJMZDOQADS-LPDFSBNLSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Agonist activity at human recombinant EP3A receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 400.56, ALogP 5.65, HBA 4, HBD 1, PSA 63.6, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: CESAWDNYOGFNBM-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 472.59, ALogP 4.67, HBA 8, HBD 0, PSA 68.54, QED 0.35
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3cc(N)nc(Cl)n3)n(C3CC3)c(=O)c12
InChIKey: UUELZCFCUBQVLU-NSHDSACASA-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 369.86, ALogP 3.84, HBA 6, HBD 2, PSA 85.83, QED 0.68
Compound (SMILES): COc1ccc(C(=O)C2CCN([C@H]3CCN(Cc4nc5c(c(=O)[nH]4)COCC5)C3=O)CC2)cc1C
InChIKey: BVCFVQGPDDYTEY-NRFANRHFSA-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 uL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 uM, 20 nM of purified enzyme, and 250 uM of p-NAD+ in the 1x Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 uL of 5x quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 uL of the 5x quenching solution per well was added prior to the addition of p-NAD+. The % Inhibition was calculated as: (Control-Sample)/(Control-Background)*100. "Control" is the average value of 8 wells without compound; and "Background" is the average of 8 wells mixed with 5x quenching solution measured prior to initiation of the reaction.
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 480.57, ALogP 1.86, HBA 7, HBD 1, PSA 104.83, QED 0.63
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3nc(N)ncc3Cl)n(-c3ccccc3)c(=O)c12
InChIKey: NHPUSQZCTRCFKS-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 405.89, ALogP 4.5, HBA 6, HBD 2, PSA 85.83, QED 0.52
Compound (SMILES): Cc1nc(C(C)(CO)NC(=O)c2cc(OCC(F)(F)F)c(C3CC3)cn2)no1
InChIKey: BVXIXFYEEHYVPR-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 400.36, ALogP 2.23, HBA 7, HBD 2, PSA 110.37, QED 0.73
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cccc(S(=O)(=O)N(C)C(C)(C)C)c4)c3n2)c1
InChIKey: FBMQVTKLCHHJLB-UHFFFAOYSA-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 489.6, ALogP 4.84, HBA 5, HBD 2, PSA 108.05, QED 0.38
Compound (SMILES): Cc1nc(-n2nnc3c2CCN(C(=O)c2cccc(C(F)(F)F)c2Cl)C3C)ncc1F
InChIKey: RSOMVWPSWKNUPN-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat 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 μl 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 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 6871 nM (pChEMBL 5.159999847412109)
Descriptors: MW 454.82, ALogP 3.94, HBA 6, HBD 0, PSA 76.8, QED 0.55
Compound (SMILES): COc1ncccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: XBFWKRPDEMLPBG-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 512.58, ALogP 2.85, HBA 9, HBD 2, PSA 140.88, QED 0.4
Compound (SMILES): C[C@@H]1CN(c2scnc2-c2nc3ccccc3[nH]2)CCN1C(=O)Cn1cnc2cccnc21
InChIKey: CCZJAXJXLVRTOE-OAHLLOKOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 458.55, ALogP 3.17, HBA 8, HBD 1, PSA 95.83, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
InChIKey: HYTZXEGJTKFHQF-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 732.81, ALogP 8.33, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3c(F)ccc(F)c3F)CC2)C1
InChIKey: ZTIHJYLZSFDTNN-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 520.52, ALogP 3.47, HBA 7, HBD 1, PSA 106.73, QED 0.4