lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc(Nc2ccc(C(C)(C)O)cn2)cc1Nc1nccc(-c2ncc(F)cn2)c1OC
InChIKey: RVSZIUKIBYCERM-HPRDVNIFSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin) assessed as reduction in IL-2 induced activity
Measurement: IC50 > 3500 nM (pChEMBL 5.455999851226807)
Descriptors: MW 505.51, ALogP 2.95, HBA 11, HBD 4, PSA 159.96, QED 0.28
Compound (SMILES): COC(=O)CN1C(=O)CC(c2ccc(Cl)cc2)C(C(=O)OCc2ccccc2OC)=C1C
InChIKey: BJGGMIJYFVDFLN-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor expressed in HEK293 cells cotransfected with pCMV AC6-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 457.91, ALogP 3.85, HBA 6, HBD 0, PSA 82.14, QED 0.59
Compound (SMILES): [2H]C([2H])([2H])CC(=O)c1cnc(Nc2cccc(C#N)n2)cc1Nc1nccc(-c2ncn(C([2H])([2H])[2H])n2)c1OC
InChIKey: JZEABWOLFVXXBU-WFGJKAKNSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding affinity to JAK2 JH1 (unknown origin)
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 455.48, ALogP 3.63, HBA 11, HBD 2, PSA 143.53, QED 0.38
Compound (SMILES): CC[C@H](C)C(=O)[C@@]1(N)CCCN(c2cnc(-c3ccc(F)c(F)c3)cc2Cn2cnc3c(N)ncnc32)C1
InChIKey: GLJXHYDKIFHSPG-RKOGDMNLSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: LC-MS/MS-Based NSD2 Enzymatic Assay: This assay employed LC-MS/MS technology to monitor the SAH production from the NSD2 enzymatic reaction. The enzymatic reaction was performed in white proxiplate plus 384-well microplate (Perkin Elmer). The reaction mixture (10 μL) were composed of 8 nM NSD2 [1-1365], 1 M SAM (USB, 10601) and 400 nM nucleosome (purified from mouse liver) in reaction buffer (20 mM Tris-HCl, pH at 8.0, 0.01% Tween 20, 10 mM MgCl2, 50 mM NaCl, 1 mM DTT, 1 mM TCEP (pH7.5)). After 90 min incubation at room temperature, 3 μL quenching solution containing 2.5% TFA with 320 nM d4-SAH was added to stop the reaction.For the inhibition assay, compound solutions were transferred into the wells by Mosquito (TTP LabTech). The inhibition assays were carried out by preincubating various concentrations of the inhibitor with 5 uL reaction mixture containing 16 nM NSD2 [1-1365] and 2 uM SAM (USB, 10601) in reaction buffer. After 20 min preincubation, 5 uL solution containing 800 nM nucleosome (purified from mouse liver) in reaction buffer was added to initiate the reaction. The reaction was stopped by 3 μL quenching solution containing 2.5% TFA with 320 nM d4-SAH after 90 min.The SAH production from the enzymatic assays were monitored by LC-MS/MS on an API 4000 triple quadrupole mass spec with Turbolon Spray (Applied Biosystem) coupled with Prominenece UFLC(Shimazu). Liquid chromatography was performed on a Chromolith FastGradient HPLC column (RP-18e, 25-2 mm, from Merck) at a flow rate of 0.8 ml/min. The column was connected directly to the turbo ion electrospray operating in the positive-ion mode. Mobile phase A is 0.1% FA and 2% methanol in water and mobile phase B is 0.1% FA in ACN. Injection volume was 3 μl and the autosampler was kept at 4 degree. SAH and d4-SAH were simultaneously monitored. Data were acquired and processed by Analyst software.To quantify the formed SAH, d4-SAH was added as internal standard (IS). A series of SAH (Sigma, A9384) solution at varying concentration (1-500 nM in reaction buffer) was mixed with quenching solution mentioned above. Then LC-MS/MS was carried out on API 4000 LC/MS/MS system to detect both SAH and d4-SAH. The plot of SAH peak area/IS peak area vs SAH concentration was used to generate the normalization factor of SAH. The SAH production from real enzymatic reaction was derived from the standard curve of SAH. The down-limit of our system for the detection of SAH is around 1-2 nM, and the linear range can reach up to 500 nM.
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 520.59, ALogP 3.71, HBA 9, HBD 2, PSA 128.84, QED 0.38
Compound (SMILES): CC(C)(C)C(=O)OC12CC3CC(CC(NC4=N/C(=C\c5ccc6ncsc6c5)C(=O)N4)(C3)C1)C2
InChIKey: KQGHLDMPONJRNE-GXHLCREISA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of N-terminal GST/His6-fused human full length CLK1 (1 to 484 residues) expressed in Sf9 cells assessed as inhibition of autophosphorylation using [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 481 nM (pChEMBL 6.320000171661377)
Descriptors: MW 478.62, ALogP 4.39, HBA 7, HBD 2, PSA 92.68, QED 0.5
Compound (SMILES): Cn1cc(-c2cn3ncnc3c(-c3ccn([C@]4(CC#N)C[C@@H](C#N)C4)c3)n2)cn1
InChIKey: NNSLCBDQDWRXOB-OYOVHJISSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) using ULight - JAK (Tyr1023) substrate incubated for 60 mins in presence of ATP by envision plate reader based analysis
Measurement: IC50 = 2420 nM (pChEMBL 5.619999885559082)
Descriptors: MW 383.42, ALogP 2.54, HBA 9, HBD 0, PSA 113.41, QED 0.53
Compound (SMILES): CCc1cc(Cl)c(OC)c(N2CCN(CC[C@H]3CC[C@H](NC(=O)NC)CC3)CC2)c1
InChIKey: IXCPWQZWEFUJGL-WGSAOQKQSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor in HEK293T cells assessed as G beta-gamma release from G alpha oA using coelenterazine h as substrate pretreated with substrate followed by compound addition measured after 10 mins by BRET analysis
Measurement: EC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 437.03, ALogP 3.91, HBA 4, HBD 2, PSA 56.84, QED 0.68
Compound (SMILES): Cc1ccccc1NC(=O)Nc1ccc(C[C@H]2NC(=O)C[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC2=O)cc1
InChIKey: QIUVOSJLYMTVAE-PFEAFMADSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Binding affinity to alpha4beta1 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in vascular cell adhesion molecule 1-induced cell adhesion coated wells by fluorescence based assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 693.8, ALogP 1.82, HBA 7, HBD 8, PSA 223.93, QED 0.2
Compound (SMILES): CC[C@H](NC(=O)c1cccs1)C(=O)Nc1nccs1
InChIKey: IKMKYPAYORLQBU-QMMMGPOBSA-N
Target: Endoplasmic reticulum chaperone BiP (SINGLE PROTEIN), Homo sapiens
UniProt: P11021
Assay: Inhibition of HspA5 (unknown origin) by FP assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 295.39, ALogP 2.35, HBA 5, HBD 2, PSA 71.09, QED 0.89
Compound (SMILES): CN(CCOCCn1c2ccccc2c2ccccc21)C(CCO)C(=O)NCc1ccccc1Cl
InChIKey: KLLRNTLWDWNCCD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 2650 nM (pChEMBL 5.579999923706055)
Descriptors: MW 494.04, ALogP 4.46, HBA 5, HBD 2, PSA 66.73, QED 0.29
Compound (SMILES): O=C1NC(NC2CCCCC2)=N/C1=C\c1ccc2scnc2c1
InChIKey: CWWGZUUBJBDHOB-ZROIWOOFSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 326.42, ALogP 3.05, HBA 5, HBD 2, PSA 66.38, QED 0.83
Compound (SMILES): Cc1nc([C@@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4ccc(Cl)c(F)c4F)nn3)[C@H]2O)n(-c2ccc3ncsc3c2)n1
InChIKey: XTZWFEUNEDHQRJ-HWLDZIHSSA-N
Target: Galectin-9 (SINGLE PROTEIN), Homo sapiens
UniProt: O00182
Assay: Inhibition of human Galectin-9
Measurement: IC50 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 575.99, ALogP 2.77, HBA 12, HBD 3, PSA 144.23, QED 0.27
Compound (SMILES): COCCC(=O)N1CCC(CCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1
InChIKey: QHLKQPDXOAFUSN-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor in HEK293T cells assessed as G beta-gamma release from G alpha oA using coelenterazine h as substrate pretreated with substrate followed by compound addition measured after 10 mins by BRET analysis
Measurement: EC50 = 6.28 nM (pChEMBL 8.199999809265137)
Descriptors: MW 428.4, ALogP 3.78, HBA 4, HBD 0, PSA 36.02, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)Nc2nc(-c3ccccc3)n(-c3ccc(F)cc3)n2)cc1
InChIKey: QVKUNAKTFMAUJW-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 480.53, ALogP 3.09, HBA 6, HBD 3, PSA 132, QED 0.37
Compound (SMILES): Cc1nc2ccc(/C=C3\N=C(NC4CCCCCC4)NC3=O)cc2s1
InChIKey: CVDZJUNTQGTGHF-YBEGLDIGSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 5625 nM (pChEMBL 5.25)
Descriptors: MW 354.48, ALogP 3.74, HBA 5, HBD 2, PSA 66.38, QED 0.64
Compound (SMILES): CC(C)(C)c1cccc(CNCC(O)CNC(=O)CC(c2ccccc2)c2ccccc2)c1
InChIKey: FHYXNOQJXBMOOA-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]-GABA uptake incubated for 10 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.62, ALogP 4.77, HBA 3, HBD 3, PSA 61.36, QED 0.42
Compound (SMILES): Cc1cc(N2CCc3c(c(C)nn3CC34CCC(NC(=O)CN5CCC5)(CC3)CC4)C2)c2cnn(C)c2n1
InChIKey: HPCFPBNBJAZIOH-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilite from human ERG (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 516.69, ALogP 3.26, HBA 8, HBD 1, PSA 84.11, QED 0.54
Compound (SMILES): CC1=C(C(=O)OCc2ccccc2)C(c2ccc(Cl)cc2)CC(=O)N1CC(C)C
InChIKey: AORYTIFNYYOLKC-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor expressed in HEK293 cells cotransfected with pCMV AC6-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 411.93, ALogP 5.33, HBA 3, HBD 0, PSA 46.61, QED 0.6
Compound (SMILES): COc1cc(Nc2c(C#N)cnc3cc(OCCON4CCN(C)CC4)c(OC)cc23)c(Cl)cc1Cl
InChIKey: HFGUPJNHEPCEHX-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of human BCR-ABL1 Q252H mutant by radiometric assay
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 532.43, ALogP 4.73, HBA 9, HBD 1, PSA 92.11, QED 0.39
Compound (SMILES): CC(C)(C)[C@H](NC(=O)CC12CC3CC(CC(C3)C1)C2)C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@H](C(=O)C(=O)NC1CC1)C1CCCCC1
InChIKey: XMTPWAPSQQBCQF-RVMYELPBSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 650.91, ALogP 4.66, HBA 5, HBD 3, PSA 124.68, QED 0.3
Compound (SMILES): CN1C(=O)CNC(=O)[C@H](N[C@@H](Cc2ccc(O)cc2)C(=O)O)CCCC/C=C/C[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)NC(=O)[C@@H]1Cc1ccccc1
InChIKey: HBLAHKGXZISRHT-ZYDDLYJDSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at NPFF1R (unknown origin) transfected in CHO cells co-expressing Galphaq15 assessed as increase in calcium mobilization by Fluo-4AM dye based assay
Measurement: EC50 = 161.7 nM (pChEMBL 6.789999961853027)
Descriptors: MW 1136.32
Compound (SMILES): COc1ccc(-c2cc(C(=O)NCc3ccc(C(=O)NO)cc3)ccn2)cc1
InChIKey: BOPYJZYHIIFOOS-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of C-terminal His-tagged human HDAC5 catalytic domain (656 to 1122 residues) expressed in Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 8492 nM (pChEMBL 5.070000171661377)
Descriptors: MW 377.4, ALogP 2.81, HBA 5, HBD 3, PSA 100.55, QED 0.45
Compound (SMILES): C[C@H]1CCN1c1nc(-c2cnn(C3CCOCC3)c2)cc(C(F)(F)F)c1C#N
InChIKey: KUXLUIMRQROHFE-LBPRGKRZSA-N
Target: Ketohexokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P50053
Assay: KHK Enzyme Activity Assay for Human KHK-C and Human KHK-A: The intrinsic potency for inhibition of KHK C or A activity may be measured using an enzymatic assay which measures the production of FIP. Compounds are prepared in DMSO and tested in a 10-point concentration curve, to create 3-fold serial dilutions of the compounds in a 96-well plate ranging from 20 μM to 1.02 nM. Enzyme is prepared in assay buffer [50 mM 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES), 10 mM potassium chloride, 100 mM magnesium chloride, 2 mM tris(2-carboxyethyl)phosphine (TCEP), 0.01% n-octyl glucoside] and incubated with compounds at RT for 15 min. The reaction is carried out in 100 μL volumes containing substrate concentrations of fructose (250 μM for KHK-C assay and 1.25 mM for KHK-A assay) and ATP (150 μM for both isoforms); which are further incubated at RT for 20 min. The reaction is then halted by the addition of stop buffer; consisting of 0.2% formic acid and 1 μg/ml 13C6-fructose-6-phosphate (13C6-F6P) internal standard. Plates are stored in −20° C. until RapidFire MS analysis.RapidFire MS Analysis for Quantitation of F1PAn Agilent 300 RapidFire automated extraction system (Agilent, Santa Clara, Calif.) with three HPLC quaternary pumps is coupled to an Agilent 6495 triple quadrupole mass spectrometer (Agilent Technologies, Santa Clara, Calif.) equipped with an electrospray ionization (ESI) interface source. The RapidFire Mass Spec system is equipped with a reusable RapidFire C18 (type C) solid-phase extraction (SPE) cartridge (G9205 Å).Solvent A, used for sample loading and washing, is 6 mM octylamine (Acros Organics 129495000) brought to pH 5.0 using acetic acid. Solvent B, used for sample elution, is 20% water in ACN containing 0.1% formic acid. Samples are sequentially analyzed by aspirating 10 μL onto the collection loop under vacuum directly from multiwell plates. The 10 μL of sample is loaded onto the C18 cartridge and washed using solvent A at a flow rate of 1.25 mL/min for 5000 ms. The retained analytes are then eluted to the mass spectrometer using solvent B at a flow rate of 1.25 mL/min for 5000 ms. The system is re-equilibrated using solvent at flow rate of 1.25 mL/min for 2000 ms.The triple quadrupole mass spectrometer is equipped with an ESI source and analytes are monitored using selected reaction monitoring (SRM) in negative mode [M−H]−. F1P is monitored at m/z 259.02/96.9 and 13C6-fructose-6-phosphate is monitored at m/z 264.99/97. The area ratio values for F1P is calculated using 13C6-fructose-6-phospate as internal standard.
Measurement: IC50 = 28.4 nM (pChEMBL 7.550000190734863)
Descriptors: MW 391.4, ALogP 3.79, HBA 6, HBD 0, PSA 66.97, QED 0.8
Compound (SMILES): COC[C@@H](CC(C)C)NC1=N/C(=C\c2ccc3c(ccn3C)c2)C(=O)N1
InChIKey: BHUDPCQAMNRYCM-FEEIMYBTSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human DYRK1B assessed as incorporation of 33Pi using [gamma-33P]-ATP measured after 60 mins by microplate scintillation counting based radiometric analysis
Measurement: IC50 = 8167 nM (pChEMBL 5.090000152587891)
Descriptors: MW 354.45, ALogP 2.66, HBA 5, HBD 2, PSA 67.65, QED 0.78
Compound (SMILES): CC(C)c1ccc(CCn2c(=O)[nH]c3c(C(N)=O)nc(-c4cccc(O)c4)nc32)cc1
InChIKey: XTSIGWYRXHESPM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human PI3Kalpha using l-a-phosphatidylinositol sodium salt and l-a-phosphatidyl-L-serine as substrate incubated for 60 mins in presence of ATP by ADP-glo kinase assay
Measurement: Ki >= 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 417.47, ALogP 2.96, HBA 6, HBD 3, PSA 126.89, QED 0.44
Compound (SMILES): CN1CCN(c2nc(N)nc(C(C)(C)[Se]c3ccc4ccccc4c3)n2)CC1
InChIKey: AZEGGJUBCUBYAM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from 5-HT7 receptor (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki = 1449 nM (pChEMBL 5.840000152587891)
Descriptors: MW 441.44
Compound (SMILES): CCOC(=O)C1Cc2nc(-c3ccc4ccccc4c3)n(-c3ccnc(N[C@H]4CCCN(C(=O)C5CC5)C4)n3)c2C1
InChIKey: SGYOIXNBCYRZBZ-BBMPLOMVSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin) incubated for 20 mins in presence of 33P-ATP
Measurement: IC50 = 2248 nM (pChEMBL 5.650000095367432)
Descriptors: MW 550.66, ALogP 4.57, HBA 8, HBD 1, PSA 102.24, QED 0.34
Compound (SMILES): O=C(O)c1ccc2c(-c3ccccc3)ccc(NS(=O)(=O)c3ccccn3)c2n1
InChIKey: FRWUOEOTYLNWQY-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Binding affinity to human recombinant MMP-2 CD assessed as inhibition constant using OMNIMMP as substrate incubated for 30 mins by fluorescence based analysis
Measurement: Ki = 7750 nM (pChEMBL 5.110000133514404)
Descriptors: MW 405.44, ALogP 3.8, HBA 5, HBD 2, PSA 109.25, QED 0.52
Compound (SMILES): Cc1ccc(CNC(=O)c2cc(/C=C/C(=O)O)cc(-c3ccc4ncnn4c3)c2)cc1
InChIKey: QJWQAZTYFYCFQU-RMKNXTFCSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of recombinant AKR1C4 (unknown origin) dehydrogenase activity by measuring NADH formation by spectrophotometry
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 412.45, ALogP 3.73, HBA 5, HBD 2, PSA 96.59, QED 0.47
Compound (SMILES): OCCc1cn(-c2ccc3c(c2)B(O)OC3)nn1
InChIKey: YCPYKMUPRIKDKJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase VII assessed as inhibition constant incubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 81.7 nM (pChEMBL 7.090000152587891)
Descriptors: MW 245.05
Compound (SMILES): CN(Cc1ccccc1)c1ncnc2[nH]c(-c3ccc(O)cc3)cc12
InChIKey: DTKVEGSQVRWLEQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 330.39, ALogP 3.97, HBA 4, HBD 2, PSA 65.04, QED 0.59
Compound (SMILES): O=C(NCC12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)c1ccc2c(ccn2Cc2ccc(C(=O)NO)c(F)c2)c1
InChIKey: XBNPUOXMQUEWOS-DMHOEKEMSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant full-length human HDAC4 using FAM-RHKK (trifluor-Ac)-NH2 as substrate by electrophoretic mobility shift assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 475.56, ALogP 4.89, HBA 4, HBD 3, PSA 83.36, QED 0.35
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)NC4CCOCC4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: PXOAPOFERXXQCH-KSVNGYGVSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3-ITD (unknown origin) using 5- FAM-EAIYAAPFAKKK-CONH2 and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 60 mins by Caliper assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 443.46, ALogP -0.67, HBA 11, HBD 4, PSA 162.57, QED 0.41
Compound (SMILES): COc1cc(C(=O)c2ccn(-c3ccc(S(N)(=O)=O)cc3)c2)cc(OC)c1OC
InChIKey: CZZVNDSYRYZFJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to human recombinant CA12 assessed as inhibition constant incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 416.46, ALogP 2.38, HBA 7, HBD 1, PSA 109.85, QED 0.59
Compound (SMILES): O=C1NC(NCC(O)C2CCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: AOGIFFVMTGMFBP-NVNXTCNLSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 370.48, ALogP 2.65, HBA 6, HBD 3, PSA 86.61, QED 0.72
Compound (SMILES): CC1(C)CCC(NC2=N/C(=C\c3ccc4ncsc4c3)C(=O)N2)CO1
InChIKey: DJHMDVUOYUYLOJ-AUWJEWJLSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 356.45, ALogP 2.67, HBA 6, HBD 2, PSA 75.61, QED 0.81
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)O)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)N2)NC1=O
InChIKey: ICCAEUZPYASGSV-HKZOMLJHSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Inhibition of rat alpha3/beta4 nAChR expressed in Stage V-VI Xenopus laevis Oocytes assessed as inhibition of acetylcholine-induced current in presence of acetylcholine by electrophysiological recording
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1487.69
Compound (SMILES): C=CC(=O)N1CCC(Oc2n[nH]c3ncc(-c4cn(-c5c(F)ccc(NS(=O)(=O)c6cccc(-c7ccccc7)c6)c5F)nn4)cc23)C1
InChIKey: BTVPMDAMCUGYJV-UHFFFAOYSA-N
Target: LIM domain kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53667
Assay: Inhibition of full length human LIMK1 by KINOMEscan assay
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 668.69, ALogP 5.12, HBA 9, HBD 2, PSA 147.99, QED 0.2
Compound (SMILES): Cl.NC(Cc1ccc(=O)n(O)c1)C(=O)O
InChIKey: JBRVHKSSAOHJOY-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Homo sapiens
UniProt: P14679
Assay: Inhibition of tyrosinase in human MNT-1 cell lysates assessed as inhibition of melanin production using L-DOPA as substrate measured after 3 hrs
Measurement: IC50 = 90000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 198.18, ALogP -0.96, HBA 5, HBD 3, PSA 105.55, QED 0.54
Compound (SMILES): C=CCN1C(=O)CC(c2ccc(Cl)cc2)C(C(=O)OCc2ccccc2)=C1C
InChIKey: SWGVTBPHHVUUGH-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor expressed in HEK293 cells cotransfected with pCMV AC6-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 395.89, ALogP 4.86, HBA 3, HBD 0, PSA 46.61, QED 0.52
Compound (SMILES): COc1ccc2sc3c(N)ccc(NCC[C@@H]4CCCN5CCCC[C@H]45)c3c(=O)c2c1
InChIKey: CFBPNQLXDNLVNE-HRAATJIYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by DTNB reagent based Ellman's method
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 437.61, ALogP 5.07, HBA 6, HBD 2, PSA 67.59, QED 0.43
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=O)N[C@@H]2CCN(c3ccccn3)C2)c1
InChIKey: GOWQSNLJQVTEQN-CYBMUJFWSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human CA7 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 361.43, ALogP 1.13, HBA 5, HBD 3, PSA 117.42, QED 0.75
Compound (SMILES): CC(=O)c1cccc(NS(=O)(=O)c2ccc(C(=O)Nc3nc(-c4cccc(F)c4)cs3)cc2)c1
InChIKey: VUAMLKVINZWIJR-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Binding affinity to PHGDH (unknown origin) assessed as dissociation constant incubated for 60 mins by microscale thermophoresis analysis
Measurement: Kd = 2330 nM (pChEMBL 5.630000114440918)
Descriptors: MW 495.56, ALogP 5.2, HBA 6, HBD 2, PSA 105.23, QED 0.34
Compound (SMILES): Cc1cccc(CN(C)c2ncnc3[nH]c(-c4cccnc4)cc23)c1
InChIKey: IQKPWLCHWJCSLF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin) using ultra ULight GT peptide as substrate incubated for 1 hr in presence of 25 uM of ATP by LANCE Ultra TR-FRET assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 329.41, ALogP 3.96, HBA 4, HBD 1, PSA 57.7, QED 0.62
Compound (SMILES): Cl.N[C@H]1CCN(c2c3c(nc4ccc(-c5ccnc(NC(=O)C6CC6)c5)cc24)CCCCCC3)C1
InChIKey: CZOPGAJLLJTGOM-BOXHHOBZSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyl thiocholine iodine as substrate for 20 mins by Ellman's method
Measurement: IC50 = 2806 nM (pChEMBL 5.550000190734863)
Descriptors: MW 455.61, ALogP 4.84, HBA 5, HBD 2, PSA 84.14, QED 0.59
Compound (SMILES): Cc1ccc(-c2noc(-c3ccc(S(=O)(=O)N[C@@H](C(=O)O)C(C)C)cc3)n2)s1
InChIKey: QZHAFOIXACHKEM-OAHLLOKOSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human recombinant MMP-13 (20 to 471 residues) expressed in NS0 cells using (7-methoxycoumarin-4-y1)-acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitropheny1)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 421.5, ALogP 3.16, HBA 7, HBD 2, PSA 122.39, QED 0.6
Compound (SMILES): N#Cc1ccc2c(=O)n(CCc3ccccc3)c(=O)n(Cc3ccc(C(=O)NO)cc3)c2c1
InChIKey: DHWJPMDGGNEXEP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Enzymatic Assay: The IC50 values for aforementioned compounds against HDACs were determined. HDAC 1 to 11 can be assayed by using acetylated AMC-labeled peptide substrate. The Substrate 1, a fluorogenic peptide from p53 residues 379-382 (RHKKAc) is used for all MAC 1 to 11 but HDAC8, which has a substrate II (RHKAcKAc), a fluorogenic diacyl peptide based on residues 179-382 of p53. Compounds were tested in 10-dose 1050 mode in duplicate with 3-fold serial dilution starting at 10 uM.
Measurement: IC50 = 13500 nM (pChEMBL 4.869999885559082)
Descriptors: MW 440.46, ALogP 2.44, HBA 7, HBD 2, PSA 117.12, QED 0.35
Compound (SMILES): O=C(NS(=O)(=O)c1ccc2oc(=O)ccc2c1)c1cc2cc(Oc3ccc(Cl)c(Cl)c3)ccc2[nH]1
InChIKey: HSNYJVWJXYJXIF-UHFFFAOYSA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Binding affinity to human Gal-3 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry analysis
Measurement: Kd = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 529.36, ALogP 5.49, HBA 6, HBD 2, PSA 118.47, QED 0.29
Compound (SMILES): NS(=O)(=O)Oc1ccc(-c2sc3cc(OS(N)(=O)=O)ccc3c2C(=O)c2ccc(OCCN3CCCCC3)cc2)cc1
InChIKey: VMIIEGLGCRYZHZ-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of [3H]estradiol from human ER-alpha expressed in Sf21 cells incubated for 120 mins by scintillation counting analysis
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 631.75, ALogP 3.83, HBA 10, HBD 2, PSA 168.32, QED 0.23
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCc1ccccn1)c1nnc(C)n1-2
InChIKey: IQSNRFQUNLCFPX-FQEVSTJZSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 491.02, ALogP 4.9, HBA 7, HBD 1, PSA 85.06, QED 0.43
Compound (SMILES): COc1cccc(NC(=S)N2CCN(c3nnc(Cc4ccccc4)c4ccccc34)CC2)c1
InChIKey: DAWLRKYDSIQUEZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by FRET assay
Measurement: IC50 = 7952 nM (pChEMBL 5.099999904632568)
Descriptors: MW 469.61, ALogP 4.75, HBA 5, HBD 1, PSA 53.52, QED 0.42
Compound (SMILES): CCC(C(=O)O)c1ccc(-c2cc(OC)cc(OC)c2)c(C(F)(F)F)c1
InChIKey: QYDNPMPQJBLJAY-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of human recombinant AKR1C4 transfected in Escherichia coli BL21 (DE3) pLysS competent cells using S-tetralol as substrate assessed as inhibition of NADP+ dependent substrate oxidation incubated for 10 mins by fluorescence microplate reader assay
Measurement: IC50 = 1270 nM (pChEMBL 5.900000095367432)
Descriptors: MW 368.35, ALogP 4.97, HBA 3, HBD 1, PSA 55.76, QED 0.78
Compound (SMILES): CC[N+](CC)(CC)CCOc1ccc(C(=O)Nc2ccccc2)cc1.[I-]
InChIKey: GMHKAKYVYDLMSS-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nAChR expressed in acetylcholine-induced Xenopus laevis oocytes assessed as peak currents treated for 1 sec at holding potential of -70 mV by two electrode voltage-clamp assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 341.48, ALogP 4.19, HBA 2, HBD 1, PSA 38.33, QED 0.69
Compound (SMILES): Cc1cc(N)nc(CCc2cc(CCN)cc(F)c2F)c1.Cl.Cl
InChIKey: ZKHCWVBBBKRPFN-UHFFFAOYSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29474
Assay: Inhibition of human eNOS expressed in Escherichia coli using human oxyhemoglobin by hemoglobin (Hb) NO capture assay
Measurement: Ki = 77158 nM (pChEMBL 4.110000133514404)
Descriptors: MW 291.35, ALogP 2.54, HBA 3, HBD 2, PSA 64.93, QED 0.89
Compound (SMILES): C=CC(=O)N1CCC(c2cc3c(Oc4ccc(NC(=O)NC5CC5)c(Cl)c4)ccnc3cc2OCC)CC1
InChIKey: KVOZGEJRFWGHFZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) incubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 535.04, ALogP 6.26, HBA 5, HBD 2, PSA 92.79, QED 0.33
Compound (SMILES): Cc1cnc(OCc2cn(-c3ccnc(C)c3)nn2)nc1
InChIKey: ZDNSEOYRLXQGFM-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: NMDA receptor FLIPR assay: NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 149 mM NaCl, 4 mM KCl, 2 mM CaCl2, and 1.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (149 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 2 mM CaCl2, 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to EC80 (standard assay) or EC40 (HTS assay) is used to maximize the assay's signal window or the ability to detect NMDA receptor antagonists and negative allosteric modulators, respectively. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 655 nM (pChEMBL 6.179999828338623)
Descriptors: MW 282.31, ALogP 1.65, HBA 7, HBD 0, PSA 78.61, QED 0.72
Compound (SMILES): Cc1cc(C(N)=O)c(-c2cccc(OC(=O)N3CCC(NCCc4ccccc4)CC3)c2)o1
InChIKey: SNNQPXKBHJFXTJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human CB2 receptor expressed in CHO cells assessed as inhibition constant incubated for 60 mins by liquid scintillation counter analysis
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 447.54, ALogP 4.15, HBA 5, HBD 2, PSA 97.8, QED 0.57
Compound (SMILES): COc1ccc(Cc2nnc(N3CCN(C(=S)Nc4ccc(Cl)cc4)CC3)c3ccccc23)cc1
InChIKey: DJOPDQNHJUNVIQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by FRET assay
Measurement: IC50 = 2168 nM (pChEMBL 5.659999847412109)
Descriptors: MW 504.06, ALogP 5.4, HBA 5, HBD 1, PSA 53.52, QED 0.37
Compound (SMILES): N[C@H]1CC[C@H](Nc2cc(Nc3ccc(S(=O)(=O)N4CCCC4)cc3)c3ncc(-c4ccccc4)n3n2)CC1
InChIKey: IOMVZMIXBDMKIE-AFARHQOCSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human FLT3-ITD-F691L mutant expressed in Sf9 insect cells using myelin basic protein and ATP as substrate in presence of [gamma-33P]ATP as substrate by radiometric assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 531.69, ALogP 4.61, HBA 8, HBD 3, PSA 117.65, QED 0.32
Compound (SMILES): Cl.Cl.Nc1ccccc1NC(=O)c1ccc(COc2ccc(CNC(=O)[C@H]3CCCN3)cc2)cc1
InChIKey: UFARUDAPUKLDQM-PPLJNSMQSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of C-terminal His-tagged human recombinant full length HDAC8 (1 to 377 residues) expressed in Sf9 cells using Ac-Leu-Gly-Lys(trifluoroAc)-AMC as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 90 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.54, ALogP 3.47, HBA 5, HBD 4, PSA 105.48, QED 0.4
Compound (SMILES): [2H]C([2H])([2H])CC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1nccc(-c2ncn(C([2H])([2H])[2H])n2)c1OC
InChIKey: ZRKHCJOUTWUZAT-WFGJKAKNSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 signal transduction pathway in human PBMC cells assessed as IFNalpha induced p-STAT5 level
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 421.46, ALogP 2.97, HBA 9, HBD 2, PSA 123.92, QED 0.53
Compound (SMILES): c1ccc(N2CCN(CCCCc3nc4ccccc4s3)CC2)nc1
InChIKey: UTXSOICYDAGUJA-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2 receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin stimulated cAMP production incubated for 30 mins by Lance ultra cAMP assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 352.51, ALogP 3.84, HBA 5, HBD 0, PSA 32.26, QED 0.63
Compound (SMILES): CCC[C@@H](C(=O)Nc1ccc(C(N)=O)c(F)c1)n1cc(OC)c(-c2cc(Cl)ccc2-n2cc(Cl)nn2)cc1=O
InChIKey: KQZYQOJQXJGZMI-NRFANRHFSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: To determine the plasma kallikrein inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic plasma kallikrein substrate to determine the enzymatic activity of human plasma kallikrein. Here, plasma kallikrein cleaves from the peptic plasma kallikrein substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions is placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 573.41, ALogP 4.63, HBA 8, HBD 2, PSA 134.13, QED 0.3
Compound (SMILES): CO[C@H]1CCC[C@H](NC2=N/C(=C\c3ccc4ncsc4c3)C(=O)N2)C1
InChIKey: IJFKKIMDRSZOOW-FLOSXWIUSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 356.45, ALogP 2.67, HBA 6, HBD 2, PSA 75.61, QED 0.83
Compound (SMILES): C[C@H]1C[C@H](NC(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)CCN1C
InChIKey: WZNBROSXRNFARP-WEJIIORJSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3-ITD (unknown origin) using fluorescein-poly GT and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 40 mins by LanthaScreen assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 470.53, ALogP -0.37, HBA 11, HBD 4, PSA 156.58, QED 0.4
Compound (SMILES): S=C([S-])NCc1cccnc1.[K+]
InChIKey: KWTULDOELMWBGF-UHFFFAOYSA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 N-terminal 6His-SUMO-tagged 3CL protease expressed in Escherichia coli BL21 (DE3) using Dabcyl-KTSAVLQSGFRKM-Glu-Edans fluorogenic peptide as substrate pre-incubated for 30 mins in presence of GSH followed by substrate addition measured after 30 mins by FRET assay
Measurement: IC50 = 1348.96 nM (pChEMBL 5.869999885559082)
Descriptors: MW 184.29, ALogP 1.39, HBA 2, HBD 2, PSA 24.92, QED 0.54
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)cc(N2CCN(C(=S)SCC(=O)N(C)C)CC2)n1
InChIKey: JXCSRHVITGYTRY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal 6xHis-tagged recombinant full-length human PI3Kdelta expressed in baculovirus infected Sf21 insect cells by ADP-Glo assay
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 606.72, ALogP 2.83, HBA 11, HBD 0, PSA 92.09, QED 0.37
Compound (SMILES): COc1ccccc1N1CCN(CCCNC(=O)Nc2ccccc2-c2cccc(F)c2)CC1
InChIKey: UYPLISCDIQJPNG-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopmaine D4.4 receptor expressed in HEK293T cells assessed as inhibition constant by competition binding assay
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 462.57, ALogP 4.84, HBA 4, HBD 2, PSA 56.84, QED 0.47
Compound (SMILES): CC(=O)N/C(N)=N/C(=N/S(=O)(=O)c1ccc(Cl)cc1)N1C[C@H](c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: MYODGSDMTZTLQA-JOCHJYFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 557.46, ALogP 3.99, HBA 4, HBD 2, PSA 129.58, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc2nc(NC(=O)CSC(=S)N3CCOCC3)sc2c1
InChIKey: GZHFJUUKPRLBLE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 26.8 nM (pChEMBL 7.570000171661377)
Descriptors: MW 432.57, ALogP 1.23, HBA 8, HBD 2, PSA 114.62, QED 0.69
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(CC1CCN(S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)CC1)C2
InChIKey: PLVJFQLTLNVOKN-VOTSOKGWSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8
Measurement: IC50 = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 514.6, ALogP 3.07, HBA 7, HBD 2, PSA 122.24, QED 0.32
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)Nc4cc(NC5CCC5)ncn4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: FWOOHCKJEYAWAX-QPXQOZNCSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3-ITD (unknown origin) using 5- FAM-EAIYAAPFAKKK-CONH2 and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 60 mins by Caliper assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 506.53, ALogP 0.43, HBA 13, HBD 5, PSA 191.15, QED 0.24
Compound (SMILES): COc1cc(F)ccc1C1CCN([C@@H]2CCC3(C2)CN(C(=O)C2COC2)C3)CC1
InChIKey: PGHIFKDWJWSHAZ-LJQANCHMSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Activation of human cloned muscarinic M4 receptor expressed in CHO-K1 cells by Calcium flux assay relative to control
Measurement: EC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 402.51, ALogP 3.04, HBA 4, HBD 0, PSA 42.01, QED 0.78
Compound (SMILES): CC(C)(O)[C@H]1CC[C@@](C)([C@H]2CC[C@]3(C)[C@@H]2[C@H](O)C[C@@H]2[C@@]4(C)CC[C@H](NC(=O)[C@@H]5CCCN5)C(C)(C)[C@@H]4CC[C@]23C)O1
InChIKey: FRLGWRYFNSFURN-VUQOTYAVSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of ABCC1 (unknown origin) overexpressing human KBV cells mediated efflux assessed as cisplatin IC50 using cisplatin as substrate at 10 uM
Measurement: IC50 = 5860 nM (pChEMBL 5.230000019073486)
Descriptors: MW 572.88, ALogP 5.59, HBA 5, HBD 4, PSA 90.82, QED 0.35
Compound (SMILES): Cc1c(OCCNCCCF)ccc(F)c1[C@@H]1c2[nH]c3ccccc3c2C[C@@H](C)N1CCC(=O)O
InChIKey: VFDFZWVNAVIIKM-XGCWNURASA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: ERalpha Binding Assay: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alphaLBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.2. Prepare 1× ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.3. Dispense 6 μL of the 1× AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 μM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 485.58, ALogP 4.75, HBA 4, HBD 3, PSA 77.59, QED 0.34
Compound (SMILES): Cc1cc(Nc2ncc(C)c(N3CC(CC#N)(OC4CC5(CC5)C4)C3)n2)sn1
InChIKey: YHBWHSCISDHNCC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin) incubated for 45 to 120 mins in presence of ATP by Kinase-Glo luminescent assay
Measurement: IC50 = 3153 nM (pChEMBL 5.5)
Descriptors: MW 396.52, ALogP 3.73, HBA 8, HBD 1, PSA 86.96, QED 0.8
Compound (SMILES): O=C(NCc1ccccc1)NC12CC3CC(CC(NCC(=O)N4Cc5ccccc5C4)(C3)C1)C2
InChIKey: QBCHCTFSFPYSDK-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of human recombinant DPP2 using Lys-Ala-pNA as substrate incubated for 15 mins by fluorescence based analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 458.61, ALogP 3.71, HBA 3, HBD 3, PSA 73.47, QED 0.62
Compound (SMILES): Cc1[nH]nc(-c2ccncc2)c1-c1cc(F)c(N2CC3(C2)CS(=O)(=O)C3)c(F)c1
InChIKey: SPZKSWFQDFPDCO-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 G2019S mutant in HEK293 cells
Measurement: EC50 = 3140 nM (pChEMBL 5.5)
Descriptors: MW 416.45, ALogP 2.96, HBA 5, HBD 1, PSA 78.95, QED 0.71
Compound (SMILES): CC(c1ccc(F)cc1)n1cc(-c2cc(F)cc3c(C#N)n[nH]c23)c(=O)[nH]c1=O
InChIKey: KKWUMHRZBSGSJW-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET D1228V in human NCI-H1993 cells incubated for 4 hrs by HTRF assay
Measurement: EC50 = 2150 nM (pChEMBL 5.670000076293945)
Descriptors: MW 393.35, ALogP 2.84, HBA 5, HBD 2, PSA 107.33, QED 0.56
Compound (SMILES): Cc1noc(C)c1COc1ccc(Cl)cc1C(=O)NCc1ccccc1
InChIKey: OUMZLWWILNNBSC-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of AKR1C4 (unknown origin) incubated for 10 mins by fluorometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.84, ALogP 4.45, HBA 4, HBD 1, PSA 64.36, QED 0.7