lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(N)=O)C(C)C
InChIKey: XHPNKAPWXFVQKQ-AEEVCGNZSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of human recombinant MMP-3 (Tyr18 to Cys477 residues ) using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 729.18, ALogP 0.65, HBA 8, HBD 7, PSA 242.96, QED 0.11
Compound (SMILES): Cc1nc(C)n(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(C(C)(C)C)nc3)C[C@H]2C)n1
InChIKey: JSLHIASGSJBGLL-CYBMUJFWSA-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 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 522.6, ALogP 3.86, HBA 9, HBD 0, PSA 92.93, QED 0.51
Compound (SMILES): N.N.Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3F)c(=O)[nH]1
InChIKey: RCXGYDPPYKVDAP-BOGCYVOXSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Mus musculus
UniProt: Q3TBT3
Assay: Agonist activity at STING HAQ variant in mouse BMDC cells assessed as increase in mouse INF-beta production incubated for 5 hrs by ELISA
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 678.4, ALogP -0.39, HBA 18, HBD 5, PSA 289.19, QED 0.17
Compound (SMILES): Clc1ccc(Nc2nc3ccccc3c3[nH]c(C4CCCCCCCC4)nc23)cc1Cl
InChIKey: VLFOIGWFHOKUEU-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 1 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 453.42, ALogP 8.38, HBA 3, HBD 2, PSA 53.6, QED 0.33
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1cnc(N)s1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RZWKIWSVEPQMPP-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 312.44, ALogP 1.46, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): Cc1nc(-c2cnc(NC3CC3)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: ZJIRIQBCHHNGDO-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-tagged PDGFRbeta (unknown origin) (557 to 1106 residues) measured by spectrophotometric analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 429.48, ALogP 3.31, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CC[C@H](N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O)C(F)(F)F
InChIKey: PKKGUQHKALIMOX-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 551.55, ALogP 2.54, HBA 8, HBD 3, PSA 151.79, QED 0.41
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](OC(=O)c2cccc3ccccc23)[C@H]1OC(=O)c1cccc2ccccc12
InChIKey: PSBROSWEMLTASJ-BQOYKFDPSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBL9
Assay: Agonist activity at human P2X2R/P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 815.52, ALogP 4.41, HBA 16, HBD 5, PSA 291.27, QED 0.08
Compound (SMILES): Nc1nnc2c([nH]c3ccccc32)c1-c1ccccc1
InChIKey: DHDZFJQQXROKLC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain 1 (unknown origin) by TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 260.3, ALogP 3.36, HBA 3, HBD 2, PSA 67.59, QED 0.55
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(C(C)C)CC3)nc12
InChIKey: VBLIZEIXBKDACF-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in rat liver membranes measured after 120 mins by scintillation counting method
Measurement: Ki = 1800 nM (pChEMBL 5.75)
Descriptors: MW 346.5, ALogP 2.96, HBA 5, HBD 1, PSA 48.47, QED 0.9
Compound (SMILES): CC1(C)c2ccc3c(c2CC[C@@H]1O)C(=O)C(=O)c1c(CO)coc1-3
InChIKey: JACUFUQZLAOSFL-ZDUSSCGKSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO in human HEK293 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate by absorbance based analysis
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 326.35, ALogP 2.4, HBA 5, HBD 2, PSA 87.74, QED 0.79
Compound (SMILES): CSc1nc(-c2cccc(NC(=O)c3c(F)ccc(O)c3CN3C(=O)c4ccccc4C3=O)c2)c(-c2ccnc(NC(C)=O)c2)[nH]1
InChIKey: HPMLKUVOVSVMID-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Displacement of sapitinib-BODIPY tracer from C-terminal NanoLuc-fused full length wild type EGFR (unknown origin) transfected in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 636.67, ALogP 5.71, HBA 8, HBD 4, PSA 157.38, QED 0.12
Compound (SMILES): CCS(=O)(=O)N1CCc2cc(C3CC3NCC3CCNCC3)ccc21
InChIKey: XXJFPDYHNSBYGX-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 363.53, ALogP 1.84, HBA 4, HBD 2, PSA 61.44, QED 0.81
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1OC
InChIKey: TZCPALNCOZRZIG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 45.3 nM (pChEMBL 7.340000152587891)
Descriptors: MW 350.44, ALogP 1.68, HBA 5, HBD 2, PSA 90.65, QED 0.71
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOc1cccc(c1)N3
InChIKey: JPUFKFLLCQBKCT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) L858R/T790M mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 353.38, ALogP 3.17, HBA 7, HBD 1, PSA 74.73, QED 0.72
Compound (SMILES): CN1CCCC1c1cc2ccc(O)cc2o1
InChIKey: STOHKMQGYFFHMS-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Partial agonist activity at low sensitivity isoform human (alpha4)3(beta2)2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response at holding potential of -50 mV by two-electrode voltage clamp technique
Measurement: EC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 217.27, ALogP 2.91, HBA 3, HBD 1, PSA 36.61, QED 0.8
Compound (SMILES): C[C@H](c1c(Cl)ccc(C2CC2)c1Cl)n1cnc2cnc(-c3ccccc3[C@@H](C)C(=O)O)cc21
InChIKey: JPJWHCNGSBCZMI-HUUCEWRRSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in HEK293 cells assessed as potentiation of GLP-1(9-36) induced cAMP accumulation in presence of IBMX
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 480.4, ALogP 7.08, HBA 4, HBD 1, PSA 68.01, QED 0.32
Compound (SMILES): COC[C@H](Cc1ccccc1)NC[C@@H](O)c1cc(C(F)(F)F)nc2c(C(F)(F)F)cccc12
InChIKey: TZXAENYIJDOHQI-HNAYVOBHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as reduction in 1'-hydroxy midazolam formation using midazolam as substrate preincubated for 20 mins in absence of NADPH followed by incubation with substrate for 10 mins by LC-MS/MS analysis
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 472.43, ALogP 5.15, HBA 4, HBD 2, PSA 54.38, QED 0.45
Compound (SMILES): Cc1ccc(CNC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCC(=O)NC(C)(C)C)NC(=O)CCNC(=O)/C(C#N)=C/c2ccco2)cc1
InChIKey: VTKSMYDOQHZUPK-CNUXCAPHSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of 20S proteasome subunit beta-1c (unknown origin) using Z-LLE-AMC as substrate and measured after 30 mins
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 668.8, ALogP 3.22, HBA 7, HBD 5, PSA 182.43, QED 0.11
Compound (SMILES): CCC1NCCc2c1[nH]c1ccc(Cl)cc21.Cl
InChIKey: BVYFDLRIZSAOFH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 234.73, ALogP 3.42, HBA 1, HBD 2, PSA 27.82, QED 0.78
Compound (SMILES): COc1ccc(-c2cn3ccc(N4CCN(C(C)C)CC4)cc3n2)c(OC)c1
InChIKey: UIQKQMIPZIGLSU-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at human TLR8 expressed in HEK-blue hTLR8 cells assessed as inhibition of CL075-induced NFkappaB activation preincubated with compound for 1 hrs followed by CL075 addition and measured next day by SEAP-based spectrophotometry assay
Measurement: IC50 = 8320 nM (pChEMBL 5.079999923706055)
Descriptors: MW 380.49, ALogP 3.55, HBA 6, HBD 0, PSA 42.24, QED 0.68
Compound (SMILES): O=C(Nc1nc2cccc(C3=CCC(NC(=O)C4CC4)CC3)n2n1)C1CC1
InChIKey: ZGAWRDQWSJYLKZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 497 nM (pChEMBL 6.300000190734863)
Descriptors: MW 365.44, ALogP 2.54, HBA 5, HBD 2, PSA 88.39, QED 0.85
Compound (SMILES): COc1ccccc1C1NCCc2c1[nH]c1ccc(F)cc21.Cl
InChIKey: JBBDRQBAZICRDT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 75.86 nM (pChEMBL 7.119999885559082)
Descriptors: MW 296.35, ALogP 3.55, HBA 2, HBD 2, PSA 37.05, QED 0.76
Compound (SMILES): Fc1ccc([SeH])cc1
InChIKey: VVMNEWGUEIWVGE-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 175.06
Compound (SMILES): Cl.Oc1ccc2[nH]c3c(c2c1)CCNC3C1CCCCC1
InChIKey: JVDOKIFUQMRXTB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 954.99 nM (pChEMBL 6.019999980926514)
Descriptors: MW 270.38, ALogP 3.64, HBA 2, HBD 3, PSA 48.05, QED 0.74
Compound (SMILES): Cl.Oc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1C(F)(F)F
InChIKey: BVXWKUHLWPQAJS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 75.86 nM (pChEMBL 7.119999885559082)
Descriptors: MW 332.32, ALogP 4.13, HBA 2, HBD 3, PSA 48.05, QED 0.63
Compound (SMILES): Cc1noc(C)c1C1NCCc2c1[nH]c1ccc(Cl)cc21.Cl
InChIKey: HJURHLPKVXLRJS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 301.78, ALogP 3.66, HBA 3, HBD 2, PSA 53.85, QED 0.72
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nn(-c2cccc(S(C)(=O)=O)c2)c2cc(Cl)ccc12
InChIKey: BNJLNJOURBJUPK-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 482.96, ALogP 3.08, HBA 10, HBD 3, PSA 165.6, QED 0.39
Compound (SMILES): Cc1ccccc1C1C(=O)N(C)c2cnc(Nc3ccc(S(N)(=O)=O)cc3)nc2N1C
InChIKey: FWEIAKDAIDQPRK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Binding affinity to wild-type human full length MST1 (M1 to F487 residues) expressed in bacterial expression system by Kinomescan method
Measurement: Kd = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 438.51, ALogP 2.33, HBA 7, HBD 2, PSA 121.52, QED 0.64
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)N5CCN(C)CC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: HIRADXZLYXUWGK-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 79.3 nM (pChEMBL 7.099999904632568)
Descriptors: MW 474.57, ALogP 3.14, HBA 6, HBD 2, PSA 99.37, QED 0.43
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccc4ncncc4c3)cc2)n(-c2ccc3ncccc3c2)n1
InChIKey: VZSXRPCZRQJQFY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of NanoLuc-tagged ABL1 wild type (unknown origin) expressed in HEK293 cells by NanoBRET TE assay
Measurement: IC50 = 64.7 nM (pChEMBL 7.190000057220459)
Descriptors: MW 529.6, ALogP 7.1, HBA 7, HBD 2, PSA 106.85, QED 0.25
Compound (SMILES): CCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: CQXIEOVFWXPEIO-RXONAPBBSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: EC50 = 6.76 nM (pChEMBL 8.170000076293945)
Descriptors: MW 3344.95
Compound (SMILES): CCCN1CCN(c2cccc(C3CCCCN3C(=O)/C=C/c3ccccc3)c2)CC1
InChIKey: LPOOUTTZIAYDSP-CCEZHUSRSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-ditolylguanidine from human sigma 2 receptor/TMEM97 transfected in human HEK293T cells assessed as inhibition constant in presence of (+)-pentazocine by radioligand competition binding assay
Measurement: Ki = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 417.6, ALogP 4.99, HBA 3, HBD 0, PSA 26.79, QED 0.62
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)N5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: UTHRHKGJHFUFBP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 25.3 nM (pChEMBL 7.599999904632568)
Descriptors: MW 461.52, ALogP 3.23, HBA 6, HBD 2, PSA 105.36, QED 0.44
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)NC5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: WRLCMSJRWBXEIO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 70.4 nM (pChEMBL 7.150000095367432)
Descriptors: MW 475.55, ALogP 3.66, HBA 6, HBD 3, PSA 114.15, QED 0.36
Compound (SMILES): NC(=O)c1ccc(OCC2CCC2)cc1F
InChIKey: VLOWWMKTNSPEAY-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Inhibition of human PARP14 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 223.25, ALogP 2.1, HBA 2, HBD 1, PSA 52.32, QED 0.85
Compound (SMILES): C[C@@H]1OCC2(CCN(c3nc4[nH]nc(-c5cccc(Cl)c5Cl)c4nc3CO)CC2)[C@@H]1N
InChIKey: WRHXPUBAPLIIDL-BBATYDOGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Enzymatic Assay: Phosphatase activity of full length wild-type PTPN11(PTPN11-WT) or PTPN11-E76K mutant enzyme was measured using the fluorogenic 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP; Molecular Probes) as the substrate. Enzyme (250 pM) was incubated with or without increasing concentrations of compounds in assay buffer (62.5 mM HEPES, 125 mM NaCl, 1 mM EDTA, 1.25 mM TECP, 0.1% BSA) for 30 min at room temperature. Reaction was initiated by addition of DiFMUP (50 μM) at room temperature in 384-well black plate with a final reaction volume of 20 uL in assay buffer. After 1 hour, DiFMUP fluorescence signal was measured (Ex:340/Em:460) using Envision plate reader. Dose-response curves were analyzed using IC50 regression curve fitting (GeneData Screener). Curves were normalized to a high controls without inhibitor, and low controls without enzyme. Results are given below in Table 1. Other compounds disclosed herein are expected to have activity similar to the results below, showing activity as PTPN11 inhibitors.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 463.37, ALogP 3.15, HBA 7, HBD 3, PSA 113.18, QED 0.55
Compound (SMILES): COC(=O)C1CCN(C(=O)Cc2ccc(NCc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: NQLDZGLJAMJTPQ-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Leishmania major
UniProt: P07382
Assay: Inhibition of recombinant Leishmania major DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 450.5, ALogP 1.15, HBA 10, HBD 3, PSA 162.24, QED 0.46
Compound (SMILES): CCc1ncc(-c2nc(C(F)(F)F)sc2N2CCN(C(=O)Cn3nc(C)nc3C)[C@H](C)C2)cn1
InChIKey: IZNYLAAYGQFRQK-GFCCVEGCSA-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 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 494.55, ALogP 3.13, HBA 9, HBD 0, PSA 92.93, QED 0.54
Compound (SMILES): O=C(O)c1ccc(CN2CCC[C@H](O[C@H](CO)c3cc(Cl)cc(Cl)c3)[C@@H]2c2ccccc2)c([N+](=O)[O-])c1
InChIKey: REDPQDQMPNUDEP-NXCFDTQHSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Activation of cGMP induced partially activated state recombinant human full length N-terminal His tagged PKG1beta expressed in Baculovirus infected Sf9 cell expression system using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 1 hr in presence of cGMP by ADP-GLO Max Assay
Measurement: EC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 545.42, ALogP 6.06, HBA 6, HBD 2, PSA 113.14, QED 0.25
Compound (SMILES): C#Cc1nc(/C=C\CCCCCC(=O)NO)cs1
InChIKey: KAKCYHAHFMDCRW-VURMDHGXSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length C-terminal his-tagged human recombinant HDAC8 expressed in Sf9 insect cells
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 264.35, ALogP 2.59, HBA 4, HBD 2, PSA 62.22, QED 0.34
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccc(OC)c(O)c4)nc(OC)nc31)[C@H](O)[C@@H]2O
InChIKey: GJBHTDNKZRHMMV-BGCLTTEDSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I] N6-4-amino-3-iodobenzyl adenosine 5-N-methyluronamide from mouse A3A receptor stably expressed in HEK293 cell membrane by radioligand inhibition assay
Measurement: Ki = 5.43 nM (pChEMBL 8.270000457763672)
Descriptors: MW 484.51, ALogP 0.23, HBA 11, HBD 5, PSA 163.88, QED 0.3
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCNCC4)c3)n2)c1Cl
InChIKey: YYCRQWMDRNTZLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 V561M mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 542.43, ALogP 4.87, HBA 11, HBD 3, PSA 123.93, QED 0.28
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc3sc4ccccc4c3c2)[C@H]1NC(C)=O
InChIKey: HLHDCHXBXBBXLH-PPJWLVRDSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes incubated for 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 58900 nM (pChEMBL 4.230000019073486)
Descriptors: MW 480.63, ALogP 5.01, HBA 5, HBD 3, PSA 87.66, QED 0.4
Compound (SMILES): NS(=O)(=O)NCCCCCCN1CCN(c2cccc(Cl)c2)CC1
InChIKey: SDQKPNOVKCPNRQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human full length 5HT7BR expressed in HEK293 cells by radioligand binding assay
Measurement: Ki = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 374.94, ALogP 1.82, HBA 4, HBD 2, PSA 78.67, QED 0.65
Compound (SMILES): COC(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN(C)CC5)c(F)c4)c3n2)[C@@H](C)C1
InChIKey: CXZJXVJPISUKMR-IYBDPMFKSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 482.56, ALogP 2.58, HBA 8, HBD 1, PSA 93.72, QED 0.61
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1ccccc1
InChIKey: CFSRLUGJCGONGU-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Thr412Asn mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 353 nM (pChEMBL 6.449999809265137)
Descriptors: MW 244.25, ALogP 2.81, HBA 3, HBD 2, PSA 66.76, QED 0.87
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCCC3)ccc12
InChIKey: PCAWJIMDNGAMRA-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Inhibition of human PARP14 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 274.32, ALogP 2.18, HBA 3, HBD 2, PSA 74.95, QED 0.9
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2cccnc21
InChIKey: UXPONYQLKCUMSK-CQSZACIVSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in mouse AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 87.1 nM (pChEMBL 7.059999942779541)
Descriptors: MW 330.43, ALogP 2.47, HBA 4, HBD 2, PSA 90.01, QED 0.85
Compound (SMILES): N.O=C(O)c1cc(-c2ccc(CNc3ccc(Br)cc3)o2)ccc1O
InChIKey: MVHXINROGSSELN-UHFFFAOYSA-N
Target: 2-Hydroxyacid oxidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UJM8
Assay: Non-competitive mixed inhibition of N-terminal His-tagged human recombinant glycolate oxidase expressed in Escherichia coli BL21 (DE3) cells assessed as inhibition constant using varying concentration of glycolate as substrate measured every 60 sec for 15 mins by Amplex red and horseradish peroxidase based fluorescence assay
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 388.22, ALogP 4.73, HBA 4, HBD 3, PSA 82.7, QED 0.59
Compound (SMILES): Cc1nc([C@@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(Br)c(F)c4)nn3)[C@H]2O)n(-c2cc(Cl)ccc2C(F)(F)F)n1
InChIKey: GGYZEYHYWHBAKR-WHCFWRGISA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Biological Assay: The Gal-3 assays were performed in 384 white Opti plates in three replicates at room temperature with gentle shaking at 250-300 rpmFrom the original stocks, 2.525× working stock concentrations of His-tagged recombinant human Gal-3 (hGal-3) and that of B-ASF were prepared. From the working stock, 20 μl of hGal-3 (15 nM) and 20 μl B-ASF (15 nM) were added to the plates. In Negative Control, only hGal-3 was added. A concentration range of 50× working stocks were prepared for the compounds in 100% DMSO. Aliquots of 1 uL of the compounds were added to the wells and pre-incubated with 20 μl hGal-3 per well for 30 minutes Then 20 μl B-ASF wereadded and incubated for another 1 hour. To detect the signal, 5 μL (final conc. of 1.0 nM) terbium labelled Anti-His antibody was added and incubated for 30 min followed by adding 5 μL (final conc. of 20 nM) Streptavidin d2 and incubation for another 1 hour. The assay signal was detected using HTRF screen protocol (Excitation wavelength=340 nm, emission wavelength=615 nm/665 nm) on Envision 2104 Multilabel Reader. Data analysed using Toolset and Curve Master. Results are reported in the experimental section (IC50 in μM).
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 665.8, ALogP 3.94, HBA 10, HBD 3, PSA 131.34, QED 0.22
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4OCc4ccc(Br)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: ZIQMWXSNQCJESQ-NKYRPOHVSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells assessed as kinetic dissociation constant by NanoBRET competition binding assay
Measurement: Kd = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 520.38, ALogP 1.75, HBA 10, HBD 4, PSA 134.78, QED 0.37
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C
InChIKey: BOHGAMFJXLBMRS-YOBLAHPSSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as increase in beta arrestin-2 recruitment incubated for 1 hr by chemiluminescence based pathHunter assay
Measurement: EC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 3267.66
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc(SCc3cnc4nc(N)nc(N)c4n3)nc2)CC1
InChIKey: WSVXHZUMXANBHW-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 89000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 454.52, ALogP 1.3, HBA 11, HBD 2, PSA 163.1, QED 0.42
Compound (SMILES): Cc1cc(-c2[nH]c3cc(F)c(C4CCNCC4)cc3c2C(C)C)ccn1
InChIKey: MFBSGNLSOOTPMO-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Inhibition Reporter Assay: HEK-Blue-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9 receptors were used for screening inhibitors of these receptors using an inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene under the control of the IFN-β minimal promoter fused to five NF-κB and AP-1-binding sites. Briefly, cells are seeded into Greiner 384 well plates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 for TLR9) and then treated with test compounds in DMSO to yield a final dose response concentration range of 0.05 nM-50 μM. After a 30 minute compound pre-treatment at room temperature, the cells are then stimulated with a TLR7 ligand (gardiquimod at a final concentration of 7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9 ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB and AP-1 which induce the production of SEAP. After a 22 hour incubation at 37° C., 5% CO2, SEAP levels are determined with the addition of HEK-Blue Detection reagent (Invivogen), a cell culture medium that allows for detection of SEAP, according to manufacturer's specifications.
Measurement: IC50 = 4720 nM (pChEMBL 5.329999923706055)
Descriptors: MW 351.47, ALogP 5.27, HBA 2, HBD 2, PSA 40.71, QED 0.67
Compound (SMILES): COc1cc(/C=C/c2cc(=O)oc3c2ccc2oc(-c4cc(OC)cc(OC)c4)cc23)cc(OC)c1
InChIKey: DXJLEIVEYFLNDY-AATRIKPKSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human LOX-5 in presence of LOX substrate solution incubated for 10 mins by Varioskan-flash microplate spectrophotometer reader
Measurement: IC50 = 13900 nM (pChEMBL 4.860000133514404)
Descriptors: MW 484.5, ALogP 6.41, HBA 7, HBD 0, PSA 80.27, QED 0.25
Compound (SMILES): COc1ccc(NC(=O)N2CCc3c(sc(NC(=O)c4cnn(C)c4)c3C#N)C2)cc1
InChIKey: WVYHDFDOBCBKGI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin)
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 436.5, ALogP 3.2, HBA 7, HBD 2, PSA 112.28, QED 0.65
Compound (SMILES): COc1ccc(CN2CCC[C@H](OCc3ccc(F)c(C)c3)C2)cc1F
InChIKey: DICPGMOKBHQFRK-SFHVURJKSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 361.43, ALogP 4.46, HBA 3, HBD 0, PSA 21.7, QED 0.76
Compound (SMILES): CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1CC(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1
InChIKey: HUAZIQKZKFNJLA-YSEMLTDISA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of recombinant human MMP3 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-N2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 986.16, ALogP 0.63, HBA 12, HBD 8, PSA 335.9, QED 0.05
Compound (SMILES): C#CCN(C)CCCOc1ccc(NC(=O)CCCCCCC(=O)NO)cc1Cl
InChIKey: YZQSYKHLPBHLSR-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8 (379 to 382 residues) using RHKKAcKAc-AMC fluorogenic peptide as substrate by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 423.94, ALogP 3.46, HBA 5, HBD 3, PSA 90.9, QED 0.18
Compound (SMILES): OC[C@H]1O[C@H](Sc2cncc(Br)c2)[C@H](O)[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@H]1O
InChIKey: FNCLKJPMEFPXOR-QFACEVIFSA-N
Target: Galectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56470
Assay: Binding affinity to C-terminal domain of human Galectin-4 assessed as dissociation constant by fluorescence polarization
Measurement: Kd = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 533.33, ALogP 2.29, HBA 9, HBD 3, PSA 113.52, QED 0.43
Compound (SMILES): CN(C1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1)c1ccccc1
InChIKey: NAYXGFSGXGZZCZ-ZROIWOOFSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-fused human recombinant DYRK1A expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 321.34, ALogP 2.38, HBA 5, HBD 1, PSA 63.16, QED 0.86
Compound (SMILES): COc1ccc(CN(C)CCCNC(=O)c2cc3ccccc3o2)cc1OC
InChIKey: PHCDGYQTXVZSOO-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Binding affinity to KOR (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 382.46, ALogP 3.7, HBA 5, HBD 1, PSA 63.94, QED 0.57
Compound (SMILES): COCCN1CCN(CCn2ccc(Nc3ncc4c(n3)C(C)Cc3nn(C)c(-c5ccccc5)c3-4)n2)CC1
InChIKey: KUQOZTZPJMJBMT-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Binding affinity to human InsR expressed in mouse IGF1R knockout MEF cells assessed as dissociation constant
Measurement: Kd = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 527.68, ALogP 3.41, HBA 10, HBD 1, PSA 89.16, QED 0.35
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](NC(C)=O)CCSSCC[C@H](C(N)=O)NC1=O
InChIKey: MWUXCBIVLGSGOO-INFFCAIZSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 1243.53
Compound (SMILES): S=c1n(CCCCCCN2CCN(c3cccc(Cl)c3)CC2)c2cccc3c2n1CCC3
InChIKey: SBPCXDBPVMPZQE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human full length 5HT7BR expressed in HEK293 cells by radioligand binding assay
Measurement: Ki = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 469.1, ALogP 6.15, HBA 5, HBD 0, PSA 16.34, QED 0.29
Compound (SMILES): Cn1c(CN2CCC(c3cccc(OCc4ccc(Cl)cc4F)n3)CC2)nc2ccc(C(=O)O)nc21
InChIKey: ZFDHZDONBOMVLZ-UHFFFAOYSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in PathHunter CHO-K1 GLP1R beta-arrestin-2 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins in absence of BETP by PathHunter assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 509.97, ALogP 4.81, HBA 7, HBD 1, PSA 93.37, QED 0.38
Compound (SMILES): CC(C)n1c(=O)n(C)c2cnc3ccc(-c4ccc(OCCCN(C)C)nc4)cc3c21
InChIKey: FBYDIXCPNMJMEZ-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay
Measurement: IC50 = 0.3981 nM (pChEMBL 9.399999618530273)
Descriptors: MW 419.53, ALogP 3.86, HBA 7, HBD 0, PSA 65.18, QED 0.43
Compound (SMILES): COc1cc(-c2cn(C)c(=O)c3cnccc23)cc(OC)c1CN1CCN(CCCCCOc2cc(-c3scnc3C)ccc2CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)CC1
InChIKey: ZAGCLFXBHOXXEN-JPTLTNPLSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15369
Assay: Co-operative binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant in the presence of BRD9-BD as complex with compound using FAM-DEALAHypYIPMDDDFQLRSF peptide as substrate by fluorescence polarization assay
Measurement: Kd = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 995.23, ALogP 6.03, HBA 14, HBD 3, PSA 180.69, QED 0.08
Compound (SMILES): C[C@@H]1CC(=O)Nc2ncnc(N3CCN(C(=O)[C@H](CNC4CC4)c4ccc(Cl)cc4)[C@@H]4C[C@@H]43)c21
InChIKey: DOJSODPNZWPNBR-PPRPKMEESA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 481, ALogP 2.9, HBA 6, HBD 2, PSA 90.46, QED 0.66
Compound (SMILES): C=CC(=O)N1CCC(C(=O)O)(c2ccc(OC)cc2)CC1
InChIKey: WZFZVGUXQHXMTJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of GST-tagged human KDM2B (604 to 660 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 289.33, ALogP 1.83, HBA 3, HBD 1, PSA 66.84, QED 0.86
Compound (SMILES): CC(C)(O)c1ccc(-c2cccc(N(CC34CCC(c5noc(C(C)(C)F)n5)(CC3)CC4)C(=O)[C@H]3C[C@](O)(C(F)(F)F)C3)c2)cc1
InChIKey: AEMZJBZKICOPPC-RNMMDBENSA-N
Target: RNA-binding protein FXR2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51116
Assay: Agonist activity at human FXR2 expressed in HEK293 cells coexpressing human FGF19 incubated for 24 hrs by ELISA analysis
Measurement: EC50 = 191 nM (pChEMBL 6.71999979019165)
Descriptors: MW 643.72, ALogP 7.5, HBA 6, HBD 2, PSA 99.69, QED 0.25
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2csc3ccccc23)C(=O)c2ccc(-c3cssc3=S)cc2)cc1
InChIKey: ZMSGRMUQJXTESS-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 582.82, ALogP 6.95, HBA 7, HBD 1, PSA 80.47, QED 0.16
Compound (SMILES): C=CC(=O)Nc1ccc2ncnc(Nc3ccc4[nH]cc(Br)c4c3)c2c1
InChIKey: ATUXFPJRTSKHFB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human EGFR L858R/T790M double mutant using GGMEDIYFEFMGG as substrate in presence of ATP by radiometric assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 408.26, ALogP 4.74, HBA 4, HBD 3, PSA 82.7, QED 0.43
Compound (SMILES): Cc1cc(NC(=O)COc2ccc(Cl)cc2Cl)n(C2CCS(=O)(=O)C2)n1
InChIKey: NVBSEMQBJVQXCV-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14654
Assay: Activation of Kir6.2 channel (unknown origin) by thallium flux assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 418.3, ALogP 2.88, HBA 6, HBD 1, PSA 90.29, QED 0.81
Compound (SMILES): FC(F)(F)c1cccc(COC2CCN(Cc3ccc4[nH]cnc4c3)CC2)c1
InChIKey: YFPRVZQGLGSZKO-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 389.42, ALogP 4.76, HBA 3, HBD 1, PSA 41.15, QED 0.68
Compound (SMILES): Cc1cc(N2CCN(C)CC2)ccc1Nc1nc(N)c(C(=O)c2c(Cl)cccc2Cl)s1
InChIKey: JDWXSDWMRKCGRC-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant full length His-tagged CDK9/Cyclin T1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 317 nM (pChEMBL 6.5)
Descriptors: MW 476.43, ALogP 5.07, HBA 7, HBD 2, PSA 74.49, QED 0.5
Compound (SMILES): O=C(NO)C(Cc1ccccc1)NS(=O)(=O)c1ccc(-c2cn(-c3ccc(-c4ccccc4)cc3)nn2)cc1
InChIKey: OTCQKJMDFJEBFM-UHFFFAOYSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP-12 (unknown origin)
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 539.62, ALogP 4, HBA 7, HBD 3, PSA 126.21, QED 0.19