lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)CCc1nc(-c2ccccc2)c(-c2cccc(Cl)c2Cl)o1
InChIKey: LLKOESCDAUXPJB-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Agonist activity at human RXRbeta transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 362.21, ALogP 5.33, HBA 3, HBD 1, PSA 63.33, QED 0.67
Compound (SMILES): C#CCN1CC(C(N)=O)Oc2ccccc21
InChIKey: MLYFLGGMOAMHEG-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 216.24, ALogP 0.37, HBA 3, HBD 1, PSA 55.56, QED 0.73
Compound (SMILES): CCC(=O)CCCCC[C@H]1NC(=O)[C@H]2CCCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](Cc2cn(OC)c3ccccc23)NC1=O
InChIKey: JWOGUUIOCYMBPV-SGTPJKRGSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human FLAG-tagged HDAC3 expressed in human HEK293F cells co-expressing His6-tagged SMRT (1 to 899 residues) using Fluor-de-lys substrate as substrate incubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 623.8, ALogP 3.07, HBA 7, HBD 3, PSA 138.84, QED 0.31
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2cc(C(=O)O)ccc2Br)c1=O
InChIKey: RUFVCBKABZGJLK-MRXNPFEDSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human recombinant DPP4 using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by fluorescence based microplate reader assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 475.34, ALogP 1.47, HBA 7, HBD 2, PSA 110.56, QED 0.63
Compound (SMILES): CN1CCN(c2cccc(Nc3nccc(-c4c[nH]c5cccnc45)n3)c2)CC1
InChIKey: IPFHPUNNVNIMJV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1/cyclin B (unknown origin) using histone 1 protein substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.48, ALogP 3.52, HBA 6, HBD 2, PSA 72.97, QED 0.56
Compound (SMILES): CCOCc1nc(O)c(-c2nnc(Cc3ccc(Cl)cn3)o2)c(O)c1-c1c(OC)cccc1OC
InChIKey: AGZKELPIAJYRDT-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 1 hr by TR-FRET assay
Measurement: EC50 = 0.023 nM (pChEMBL 10.640000343322754)
Descriptors: MW 498.92, ALogP 4.4, HBA 10, HBD 2, PSA 132.85, QED 0.34
Compound (SMILES): CN(CCC=C1c2ccccc2CCc2ccccc21)C(CCN)C(=O)NCc1ccc(Cl)cc1
InChIKey: MEYQZEAPWOENKX-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 5128.61 nM (pChEMBL 5.289999961853027)
Descriptors: MW 488.08, ALogP 5.23, HBA 3, HBD 2, PSA 58.36, QED 0.43
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(Oc4[nH]nnc4C(=O)O)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: DBJCYAKNWIURTJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Mus musculus
UniProt: P06151
Assay: Inhibition of recombinant mouse LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 657.64, ALogP 3.77, HBA 11, HBD 4, PSA 216.27, QED 0.16
Compound (SMILES): NS(=O)(=O)c1ccc(NC2CCN(c3ccccc3)C2=O)cc1
InChIKey: GMEWFLAMITTXEF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 331.4, ALogP 1.55, HBA 4, HBD 2, PSA 92.5, QED 0.89
Compound (SMILES): CCCNNC(=O)N[C@H]1CC(C(=O)O)=C[C@@H](OC(CC)CC)[C@@H]1NC(C)=O
InChIKey: GDCXEZBHTKSNCZ-ARFHVFGLSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (strain A/USSR/90/1977 H1N1)
UniProt: P03469
Assay: Inhibition of Influenza A virus (A/California/04/2009 (H1N1)) Neuraminidase H274Y mutant using MUNANA as substrate preincubated for 5 to 15 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometric method
Measurement: IC50 = 384 nM (pChEMBL 6.420000076293945)
Descriptors: MW 384.48, ALogP 1.06, HBA 5, HBD 5, PSA 128.79, QED 0.28
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@@H]1[C@@H]2C[C@H](Oc3ccnc4cccnc34)C[C@@H]21
InChIKey: QWHNGHDNBOPCLG-STJUPPKHSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse Panc02 cells incubated for 48 hrs by RFMS method
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 421.93, ALogP 4.9, HBA 4, HBD 1, PSA 64.11, QED 0.61
Compound (SMILES): Cc1ccc(COC2CN(C(=O)[C@H]3C[C@]4(COC(=O)N4)C3)C2)cc1Cl
InChIKey: AKBHYCHPWZPGAH-QGGXVJLZSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in Expi293 cells using p-nitrophenyl acetate as substrate incubated for 30 mins by spectrophotometry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.83, ALogP 2.26, HBA 4, HBD 1, PSA 67.87, QED 0.89
Compound (SMILES): COc1nc2ccc3c(c2n1CCNC(C)=O)CCO3
InChIKey: HIZPNVPXLSHAHA-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cells assessed as increase in forskolin induced cAMP production incubated at 37 degreeC by HitHunter-cAMP assay
Measurement: EC50 = 0.042 nM (pChEMBL 10.380000114440918)
Descriptors: MW 275.31, ALogP 1.12, HBA 5, HBD 1, PSA 65.38, QED 0.91
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]c(C(=O)N5CCN(C)CC5)cc4c3N(C)C2=O)c1F
InChIKey: XNSPFEJRLDJPIA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) 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 for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 500.51, ALogP 2.82, HBA 6, HBD 1, PSA 94.24, QED 0.59
Compound (SMILES): Cc1c(O)ccc2c(O)c(NC(=O)c3ccc(O)c(CCC(C)C)c3)c(=O)oc12
InChIKey: JJEYPKKXPKNPIS-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ8
Assay: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3B by time-resolved FRET assay
Measurement: Ki = 28100 nM (pChEMBL 4.550000190734863)
Descriptors: MW 397.43, ALogP 4.06, HBA 6, HBD 4, PSA 120, QED 0.48
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3S(=O)(=O)c2ccc(C(F)(F)F)cc2)nc1-c1cnn(CCC#N)c1
InChIKey: BNXOIVMMIFOVPX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 (866 to end residues) using GEEPLYWSFPAKKK as substrate after 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 553.57, ALogP 5.08, HBA 8, HBD 1, PSA 116.8, QED 0.34
Compound (SMILES): CNC(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: PKHDPGAMOUIIJK-QKNQBKEWSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 570.5, ALogP 5.44, HBA 3, HBD 2, PSA 75.27, QED 0.38
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3ccc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: GEZPDKBNSBNCLH-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase assessed as reduction in relaxation of supercoiled pNO1 DNA measured after 30 mins by fluorescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 370.22, ALogP 4.19, HBA 4, HBD 3, PSA 95.08, QED 0.64
Compound (SMILES): COc1ccc(C)cc1-n1nnc(S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1N
InChIKey: PIUANHUFEHCJIG-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs in presence of 5 uM rifampicin by luciferase reporter assay
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 400.5, ALogP 3.3, HBA 7, HBD 1, PSA 100.1, QED 0.72
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc(C3NCCc4ccc(Cl)cc43)c(Cl)s2)C[C@@H]1O
InChIKey: WJVMLOURSYSAQY-BNSLVSHRSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBE0
Assay: Inhibition of SAE in human HCT116 cells assessed as reduction in redistribution of SUMO2/3 proteins from nucleus to cytosol incubated for 4 hrs by immunofluorescence assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 598.53, ALogP 3.08, HBA 10, HBD 4, PSA 156.53, QED 0.29
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3ccnc(NC(=O)CN(C)C)c3)cc2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: NCYONVSVKQVALR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of recombinant human Axl expressed in mouse BaF3 cells assessed as reduction in cell viability incubated for 2 days by cell titer glo assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 560.59, ALogP 3.66, HBA 9, HBD 2, PSA 127.56, QED 0.32
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)N2C[C@H](O)CC2C(=O)[C@H](NC(=O)C2(F)CC2)C(C)(C)C)c(OCCOCc2cn(CCOc3ccc(Cn4c(-c5ccc(O)cc5)c(C)c5cc(O)ccc54)cc3)nn2)c1
InChIKey: VYYKTWKDERPACN-FFDUFJBXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha S463P mutant (unknown origin) expressed in Escherichia coli preincubated for 15 mins followed by ligand addition and measured after 1 hr by fluorescent polarization assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 1029.2
Compound (SMILES): Cc1c(COc2cc(OCc3cncc(C#N)c3)c(CN(CCCN(C)C)CCS(=O)(=O)O)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: QJSJWFVBDAPNAE-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PD-L1 interaction (unknown origin) by AlphaLISA assay relative to control
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 721.28, ALogP 6.15, HBA 10, HBD 1, PSA 134.45, QED 0.13
Compound (SMILES): CCOc1cccnc1Oc1cncc(-c2ncc(C(=O)N[C@@H]3CNCC(F)(F)C3)cn2)c1
InChIKey: STEOFTXCZZHZJZ-INIZCTEOSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro Assay: For determination of IC50 values, the reactions were carried out in 384-well white polypropylene plates (Nunc) in a total volume of 20 μL. To 1 μL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 μL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 15 minutes. hDGAT2 membrane fractions were diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical, dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock). 10 μL of this enzyme working solution was added to the plates and incubation continued for 2 hours at room temperature. DGAT2 reactions were initiated by the addition of 4 μL of substrates containing 30 μM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 μM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 μL of 1% H3PO4. After the addition of 45 μL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 minute in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 456.45, ALogP 2.85, HBA 8, HBD 2, PSA 111.15, QED 0.56
Compound (SMILES): CCc1cnc(NC(=O)c2cc3c(nc2OC)nc(C(O)(c2ccccc2)c2ccccc2)n3CC)o1
InChIKey: HSHKHTIZIQXZAX-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into histones by microbeta scintillation counting analysis
Measurement: IC50 = 0.01 nM (pChEMBL 11)
Descriptors: MW 497.56, ALogP 4.55, HBA 8, HBD 2, PSA 115.3, QED 0.32
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NCCN1CCN(C(=O)CCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ODEXJVNPPCASDJ-PHRONXMNSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from human muscarinic M4 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 588.84 nM (pChEMBL 6.230000019073486)
Descriptors: MW 859.09, ALogP 1.44, HBA 11, HBD 8, PSA 251.42, QED 0.05
Compound (SMILES): C#CC(=O)N1CCC(c2cnn3c(C(N)=O)c(-c4ccc(Oc5ccccc5OC)cc4)[nH]c23)C1
InChIKey: BAYUMEAMGPZXKA-UHFFFAOYSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of N-terminal GST-tagged BMX (1 to 675 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 469.5, ALogP 3.18, HBA 6, HBD 2, PSA 114.95, QED 0.42
Compound (SMILES): COc1ccc(F)cc1C1CC1CNCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: GZSCSKUGXORHGO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 4.21 nM (pChEMBL 8.380000114440918)
Descriptors: MW 396.46, ALogP 3.84, HBA 4, HBD 2, PSA 63.35, QED 0.54
Compound (SMILES): C[C@@H](C[C@@]1(C2CC2)NC(=O)NC1=O)C(=O)N1CCN(c2ccc(F)c(F)c2)[C@@H](C)C1
InChIKey: RKYYWBHSYPIJKC-BYVOGVQKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 420.46, ALogP 2.02, HBA 4, HBD 2, PSA 81.75, QED 0.71
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccccc3OC)n2)cc1
InChIKey: MZKCTWNUCVKGCB-UHFFFAOYSA-N
Target: Protein-tyrosine kinase 2-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q14289
Assay: Inhibition of Pyk2 (unknown origin) measured after 40 mins by HTRF
Measurement: IC50 = 24.47 nM (pChEMBL 7.610000133514404)
Descriptors: MW 417.39, ALogP 4.35, HBA 6, HBD 3, PSA 88.17, QED 0.55
Compound (SMILES): CN(CCC=C1c2ccccc2-c2ccccc21)C(CCO)C(=O)NCc1ccccc1Cl
InChIKey: QAJPGPJUFIXPGH-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 16218.1 nM (pChEMBL 4.789999961853027)
Descriptors: MW 461.01, ALogP 5.14, HBA 3, HBD 2, PSA 52.57, QED 0.36
Compound (SMILES): CCCCCCCCCCCCCCOCC(CNC(=O)[C@H](CCCCN)NC(C)=O)OCCCCCCCCCCCCCC.Cl
InChIKey: LXNYLOWTXJFIKY-NSWCCMNESA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Inhibition of TNFalpha (unknown origin) in HEK-Blue-hTLR2 cells assessed as inhibition of TNFalpha-induced NFkappaB activation pretreated for 2 hrs followed by incubation with TNFalpha for 18 hrs by SEAP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 654.08, ALogP 9.54, HBA 5, HBD 3, PSA 102.68, QED 0.06
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6ccc(O)cc6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: CGKGFXLBGZLTOO-BNZUBNTLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 16.1 nM (pChEMBL 7.789999961853027)
Descriptors: MW 578.75, ALogP 6.41, HBA 6, HBD 2, PSA 63.19, QED 0.32
Compound (SMILES): O=C(CCCN1CCN(c2ccccn2)CC1)c1ccc2c(c1)CCC2
InChIKey: OJFGNESHNMETMU-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human dopamine D3 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 349.48, ALogP 3.36, HBA 4, HBD 0, PSA 36.44, QED 0.75
Compound (SMILES): COc1cccc2cc(S(N)(=O)=O)c(=O)oc12
InChIKey: FAYOQNPFCPWXBX-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 prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 87.9 nM (pChEMBL 7.059999942779541)
Descriptors: MW 255.25, ALogP 0.45, HBA 5, HBD 1, PSA 99.6, QED 0.79
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]cnc4c3N(C)C2=O)c1F
InChIKey: TZMMPGOEQVZVGB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) 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 for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 375.34, ALogP 2.83, HBA 5, HBD 1, PSA 83.58, QED 0.76
Compound (SMILES): CCCCc1nc(=O)c(C(=O)N2CCC(c3ccccn3)C2)c(O)n1-c1c(OC)cccc1OC
InChIKey: ATBDLSRTTBGEPS-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JHG3
Assay: Agonist activity at rat APJ receptor expressed in HEK293T cells assessed as compound stimulated inhibition of forskolin stimulated cAMP production incubated for 30 mins by HTRF assay
Measurement: EC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 478.55, ALogP 3.32, HBA 8, HBD 1, PSA 106.78, QED 0.53
Compound (SMILES): Nc1nc(Cl)c2c(n1)N(Cc1ccc(C(F)(F)F)cc1)C(=O)C2
InChIKey: RFNSMFOUHVZBMK-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal Grp94 (unknown origin) incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 342.71, ALogP 2.82, HBA 4, HBD 1, PSA 72.11, QED 0.85
Compound (SMILES): C[n+]1ccc2c(c1)c1cc(F)ccc1n2CCC(=O)N1c2ccccc2Sc2ccccc21.[I-]
InChIKey: UFUNJAXKRQLFJP-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of recombinant equine BChE by Ellman's method
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 454.55, ALogP 5.98, HBA 3, HBD 0, PSA 29.12, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C(/CS(=O)(=O)c2ccccc2)c2ccc(Br)cc2)cc1
InChIKey: KQXLDCJHTCXEGO-GFMRDNFCSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 by stopped-flow CO2 hydration assay
Measurement: Ki = 8167 nM (pChEMBL 5.090000152587891)
Descriptors: MW 508.42, ALogP 3.39, HBA 6, HBD 2, PSA 118.69, QED 0.37
Compound (SMILES): CNC(=O)c1cc(-n2ncc3cc(Nc4ccccc4Cl)c(F)cc32)cs1
InChIKey: XMMMCYBZGARUKP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of JNK2 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 400.87, ALogP 4.98, HBA 5, HBD 2, PSA 58.95, QED 0.51
Compound (SMILES): Cc1ccn(-c2ccc(N3CCN(CCCCCc4c[nH]c5ccc(C#N)cc45)CC3)cc2)c(=O)c1
InChIKey: JIQDQLNNYZEFOF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Human 5-HT1A Receptor Binding Assay: Human HEK-293 cell homogenates (36 μg protein) were incubated at 22° C. for 60 minutes with 0.3 nM [3H]8-0H-DPAT (Perkin-Elmer) in the absence or presence of the test compound in a buffer solution containing 50 mM Tris-HCl (pH 7.4), 10 mM MgSO4, 0.5 mM EDTA and 2 μg/ml aprotinine.The non-specific binding value was determined by incubating the same mixture in the presence of 10 μM 8-OH-DPAT, which was used as the standard reference compound and tested in each experiment at several concentrations to obtain a competition curve.Following the incubation, the samples were filtered rapidly under vacuum through glass fiber filter (GF/B, Packard) presoaked with 0.3% PEI and rinsed several times with ice-cold 50 mM Tris-HCl using a 96-sample cell harvester (Unifilter, Packard). The filters were dried and the retained radioactivity was measured in a scintillation counter (Topcount, Packard) using a scintillation cocktail (Microscint 0, Packard). The experimental results were expressed as a percent inhibition of the control radioligand specific binding.Data AnalysisBinding assay of [3H] 8-OH-DPAT (0.3 nM) with 5-HT1A receptor in human HEK-293 cell was tested by scintillation proximity assay of membrane. The test compounds were required to be tested at least three times in the case of the concentration thereof being greater than 6 log, and the obtained data were subjected to a nonlinear regression analysis via a curve of Hill equation, to obtain IC50 value, and then calculated by ChengPrusoff equation to obtain Ki value, and Ki was the inhibition constant.
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 479.63, ALogP 5.03, HBA 5, HBD 1, PSA 68.06, QED 0.36
Compound (SMILES): Cc1cc(CNC(=O)c2cc3c(Cl)nc(Cl)cc3[nH]2)ncc1-c1cn(C)nc1C
InChIKey: RAAZRTAWLIDXSI-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 429.31, ALogP 4.21, HBA 5, HBD 2, PSA 88.49, QED 0.48
Compound (SMILES): CCOC(=O)N1CCN(c2nccc(OCc3cn(-c4ccc(S(N)(=O)=O)cc4)nn3)n2)CC1
InChIKey: WNYZMUAMUDIOAK-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 measured by stopped flow CO2 hydrase assay
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 488.53, ALogP 0.56, HBA 11, HBD 1, PSA 158.66, QED 0.5
Compound (SMILES): Cc1cc2c(C3=CCOCC3)cnc(NC3CCN(CC(F)(F)CN)CC3)c2[nH]c1=O
InChIKey: CSLBGKLETZVQLB-UHFFFAOYSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of Halo-tagged histone H4 from NanoLuc-tagged TAF1 bromodomain 2 (unknown origin) expressed in HEK293 cells measured after 4 to 6 hrs by NanoBRET assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 433.5, ALogP 2.51, HBA 6, HBD 3, PSA 96.27, QED 0.65
Compound (SMILES): CCN(c1ccc(C)cc1)S(=O)(=O)C1CC2OC1C(c1ccc(NC(=O)CCCCCCC(=O)O)cc1)=C2c1ccc(O)cc1
InChIKey: DAKDMEGAKNIPPP-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha (unknown origin) expressed in human HEK293T cells assessed as inhibition of 17beta-estradiol-induced transcriptional activities by measuring ERE driven reporter gene expression measured after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 2080 nM (pChEMBL 5.679999828338623)
Descriptors: MW 632.78, ALogP 6.37, HBA 6, HBD 3, PSA 133.24, QED 0.18
Compound (SMILES): Cn1ccc(-n2nc(CCC(=O)O)cc2-c2cc(Cl)cc(Cl)c2)n1
InChIKey: LAWBOFSGWMPKIF-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Agonist activity at human RXRgamma transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 365.22, ALogP 3.6, HBA 5, HBD 1, PSA 72.94, QED 0.75
Compound (SMILES): C=CCN(c1ccnc(Nc2ccc(C#N)cc2)n1)c1c(F)cc(-c2ccc(C#N)cc2)cc1F
InChIKey: LPSFBHDXKYGKNM-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 p66/p51 reverse transcriptase Y181C mutant incubated for 40 mins by picogreen dye-based spectrofluorometric analysis
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 464.48, ALogP 6.23, HBA 6, HBD 1, PSA 88.63, QED 0.33
Compound (SMILES): O=C(O)CCc1nc(-c2ccccc2)c(-c2cc(Cl)cc(Cl)c2)o1
InChIKey: MNBKLGOJIXFSTI-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Agonist activity at human RXRgamma transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 362.21, ALogP 5.33, HBA 3, HBD 1, PSA 63.33, QED 0.67
Compound (SMILES): O=C1NC(=O)C(CCC(=O)N2CCN(c3cc(Cl)cc(Cl)c3)CC2)(c2ccccn2)N1
InChIKey: ZAZABNIPHQNPKB-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of human recombinant TACE (AA34 to 660) assessed as cleavage of fluorescent substrate using 5FAM-LAQAVRSSSRK-5TAMRA as substrate by biochemical assay
Measurement: IC50 = 2709 nM (pChEMBL 5.570000171661377)
Descriptors: MW 462.34, ALogP 2.55, HBA 5, HBD 2, PSA 94.64, QED 0.67
Compound (SMILES): COc1ncc(-c2cc(OC3CN(C(=O)C4CC4)C3)cc3c2CNC3=O)cc1NS(C)(=O)=O
InChIKey: MYGOQAOTLYDFSH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by HTRF assay
Measurement: IC50 = 768 nM (pChEMBL 6.119999885559082)
Descriptors: MW 472.52, ALogP 1.37, HBA 7, HBD 2, PSA 126.93, QED 0.62
Compound (SMILES): O=C(O)CCCCCCC(=O)Nc1ccc(C2=C(c3ccc(O)cc3)C3CC(S(=O)(=O)N(CC(F)(F)F)c4ccccc4)C2O3)cc1
InChIKey: FBNIQANOMUQHTG-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha (unknown origin) expressed in human HEK293T cells assessed as inhibition of 17beta-estradiol-induced transcriptional activities by measuring ERE driven reporter gene expression measured after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 672.72, ALogP 6.61, HBA 6, HBD 3, PSA 133.24, QED 0.16
Compound (SMILES): CC1=CC2Cc3nc4cc(Cl)ccc4c(NCCCCCNC(=O)[C@@H](N)Cc4c[nH]c5ccccc45)c3C(C1)C2.Cl.Cl
InChIKey: OAOMAHMBSFTYHQ-XECVZFJYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of recombinant human nNOS
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 556.15, ALogP 6.63, HBA 4, HBD 4, PSA 95.83, QED 0.13
Compound (SMILES): CC(C)(C)c1cccc(CNC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)C(c2ccccc2)c2ccccc2)c1
InChIKey: FDZZTBAHBJUANF-AJQTZOPKSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 520.72, ALogP 5.99, HBA 3, HBD 3, PSA 61.36, QED 0.23
Compound (SMILES): COc1ccccc1C(C)Sc1nc2c(cnn2C)c(=O)n1-c1ccccc1
InChIKey: BYSOWZJJIJXMCF-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of human ALDH1A3 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 392.48, ALogP 3.98, HBA 7, HBD 0, PSA 61.94, QED 0.38
Compound (SMILES): O=S(=O)(N[C@H]1CCCC[C@@H]1N1CCC(c2ccccc2)CC1)c1ccccc1
InChIKey: WHCSPEJJPAHNND-GOTSBHOMSA-N
Target: Mucolipin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDD5
Assay: Activation of human TRPML3-YFP expressed in HEK293 cells incubated for 10 mins by Fluo-4 dye calcium imaging based FLIPR analysis
Measurement: EC50 = 20700 nM (pChEMBL 4.679999828338623)
Descriptors: MW 398.57, ALogP 4.16, HBA 3, HBD 1, PSA 49.41, QED 0.82
Compound (SMILES): Cc1cccc(C)c1-c1ccc2nc(NC(=O)[C@@H]3C[C@@H]3F)sc2c1.O=CO
InChIKey: WQXOMPNJSBHBJQ-DFQHDRSWSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of recombinant human c-Kit assessed as luminescence using poly (4:1 Glu, Tyr) peptide as substrate incubated for 2 hrs by ADP-Glo assay
Measurement: IC50 = 8405.03 nM (pChEMBL 5.079999923706055)
Descriptors: MW 340.42, ALogP 4.88, HBA 3, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): Cn1ncc2c(=O)n(-c3ccccc3)c(CNc3cccc(F)c3)nc21
InChIKey: ABEDOENBIFRRGQ-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of human ALDH1A3 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 349.37, ALogP 2.87, HBA 6, HBD 1, PSA 64.74, QED 0.62
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)ncc1nc(N(C)C)n(CC3CCOCC3)c12
InChIKey: HCEZPGCCFZDDQO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human whole blood assessed as reduction in LPS-induced IL-6 secretion preincubated for 30 mins followed by LPS stimulation and measured after 24 hrs by MSD assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 435.53, ALogP 4.36, HBA 8, HBD 0, PSA 78.44, QED 0.46
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(I)cc1)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: ZAXQEAJPJNIAPN-CUPIEXAXSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse MC4R expressed in HEK293 cells assessed as induction of cAMP level incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 958.64, ALogP 2.78, HBA 6, HBD 8, PSA 221.39, QED 0.03
Compound (SMILES): CN(Cc1ccc2nccn2c1)c1nnc(-c2ccc(C3CC3)cc2)o1
InChIKey: VUMTXYYRZQPYQS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by LC-MS analysis
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 345.41, ALogP 3.9, HBA 6, HBD 0, PSA 59.46, QED 0.55
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCN3CCN(c4ccc(-n5ccc6ccccc6c5=O)cc4)CC3)c2c1
InChIKey: HPAQZIMCOCMLHZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Human 5-HT1A Receptor Binding Assay: Human HEK-293 cell homogenates (36 μg protein) were incubated at 22° C. for 60 minutes with 0.3 nM [3H]8-0H-DPAT (Perkin-Elmer) in the absence or presence of the test compound in a buffer solution containing 50 mM Tris-HCl (pH 7.4), 10 mM MgSO4, 0.5 mM EDTA and 2 μg/ml aprotinine.The non-specific binding value was determined by incubating the same mixture in the presence of 10 μM 8-OH-DPAT, which was used as the standard reference compound and tested in each experiment at several concentrations to obtain a competition curve.Following the incubation, the samples were filtered rapidly under vacuum through glass fiber filter (GF/B, Packard) presoaked with 0.3% PEI and rinsed several times with ice-cold 50 mM Tris-HCl using a 96-sample cell harvester (Unifilter, Packard). The filters were dried and the retained radioactivity was measured in a scintillation counter (Topcount, Packard) using a scintillation cocktail (Microscint 0, Packard). The experimental results were expressed as a percent inhibition of the control radioligand specific binding.Data AnalysisBinding assay of [3H] 8-OH-DPAT (0.3 nM) with 5-HT1A receptor in human HEK-293 cell was tested by scintillation proximity assay of membrane. The test compounds were required to be tested at least three times in the case of the concentration thereof being greater than 6 log, and the obtained data were subjected to a nonlinear regression analysis via a curve of Hill equation, to obtain IC50 value, and then calculated by ChengPrusoff equation to obtain Ki value, and Ki was the inhibition constant.
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 487.61, ALogP 5.1, HBA 5, HBD 1, PSA 68.06, QED 0.36
Compound (SMILES): O=c1c2cc(F)ccc2nc([C@@H](Nc2ncnc3nc[nH]c23)C2CC2)n1-c1ccccc1
InChIKey: LMXZAHWOXLADSH-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human full length His-tagged p110gamma expressed in baculovirus expression system measured after 60 mins in presence of ATP by ATP-competitive binding assay
Measurement: IC50 = 29.2 nM (pChEMBL 7.539999961853027)
Descriptors: MW 427.44, ALogP 3.75, HBA 7, HBD 2, PSA 101.38, QED 0.44
Compound (SMILES): CCN(CCCCCCOc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1)Cc1ccc(N(C)C)cc1
InChIKey: BGGZRXBHDUAVMK-PXLXIMEGSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 7950 nM (pChEMBL 5.099999904632568)
Descriptors: MW 543.75, ALogP 6.88, HBA 6, HBD 1, PSA 56.25, QED 0.12
Compound (SMILES): NCCN1CCN(C(=O)CCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WLEBHKBPXJIRBW-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from human muscarinic M4 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1513.56 nM (pChEMBL 5.820000171661377)
Descriptors: MW 532.69, ALogP 2.9, HBA 6, HBD 2, PSA 102.22, QED 0.54
Compound (SMILES): CC(C)Nc1nc(N[C@H]2CC[C@H](O)CC2)ncc1C(N)=O
InChIKey: NSPCSJPGLMJDCZ-MGCOHNPYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of JNK2 (unknown origin) assessed as reduction in phosphorylated ULight-labeled 4EBP1 peptide measured after 1 hr by time-resolved fluorescence assay
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 293.37, ALogP 1.11, HBA 6, HBD 4, PSA 113.16, QED 0.65
Compound (SMILES): CCc1cc(Nc2nc(NCc3ccc(Cl)cc3)nc3cccc(OC)c23)n[nH]1
InChIKey: GHDFCDSHKKEZJV-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of recombinant human IGF-1R (959 to end residues) using KKKSPGEYVNIEF as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.89, ALogP 4.93, HBA 6, HBD 3, PSA 87.75, QED 0.4
Compound (SMILES): Cc1ncc([N+](=O)[O-])n1CCS(N)(=O)=O
InChIKey: HPDMRPQONKGFDR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 = 642.6 nM (pChEMBL 6.190000057220459)
Descriptors: MW 234.24, ALogP -0.61, HBA 6, HBD 1, PSA 121.12, QED 0.55
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)N1CCc3ccc(cc3C1)-c1ccnc3ccc-2cc13
InChIKey: AZNXDDUMHYOLFX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 548.62, ALogP 5.29, HBA 6, HBD 1, PSA 101.49, QED 0.31
Compound (SMILES): Fc1ccc(-c2n[nH]cc2N2CCNCC2)cc1
InChIKey: KJWRYKGBTQVLKK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as reduction in cAMP accumulation incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 246.29, ALogP 1.63, HBA 3, HBD 2, PSA 43.95, QED 0.85
Compound (SMILES): CC1(C)CCN(Cc2ccc(C(=O)NO)cc2)c2ccc(F)cc21
InChIKey: MLSIYEUXIKUUSS-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human HDAC6 expressed in baculovirus infected Sf9 insect cells using RHKKAc fluorogenic peptide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence assay
Measurement: IC50 = 21100 nM (pChEMBL 4.679999828338623)
Descriptors: MW 328.39, ALogP 3.63, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): FC(F)c1cncc(-c2ccc3ncc4nnc([C@H]5[C@@H]6CCC[C@@H]65)n4c3c2)c1
InChIKey: MQXVMMLHAWPDPI-QWHZDKJVSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI-amide as substrate incubated for 60 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 377.4, ALogP 4.79, HBA 5, HBD 0, PSA 55.97, QED 0.52
Compound (SMILES): Cn1nccc1-c1c(-c2cccc(C#N)c2F)nc(N)c2nn(Cc3ccccn3)nc12
InChIKey: WDIMPXNTABEEDG-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Adenosine A2B Receptor Cyclic AMP GS Assay: Stably transfected HEK-293 cells expressing the human adenosine A2B receptor (Perkin Elmer) were maintained in MEM culture medium with 10% FBS and 100 μg/mL Geneticin (Life Technologies). 18 to 24 hours prior to assay, geneticin was removed from culture. The cisbio cAMP-GS Dynamic kit utilizing the FRET (Fluorescence Resonance Energy Transfer) technology was used to measure cAMP accumulation in the cells. Compounds of the present disclosure at an appropriate concentration were mixed with 10000 cells/well in white 96 well half area plates (Perkin Elmer) for 30 min at room temperature gently shaking. Agonist, NECA (R&D Technologies) at 12 nM was added to each well for 60 min at room temperature gently shaking. Detection reagents, d2-labeled cAMP (acceptor) and anti-cAMP cryptate (donor) were added to each well for 60 min at RT gently shaking. Plates were read on Pherastar (BMG Labtech), fluorescence ratio 665/620 was calculated and EC50 determination was performed by fitting the curve of percent of control versus the log of the compound concentration using GraphPad Prism.
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 425.43, ALogP 2.93, HBA 9, HBD 1, PSA 124.12, QED 0.47
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3ncnc4c3CN(C)C4)c(F)c2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: VPIBZEMGXNTWKR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Mus musculus
UniProt: Q60805
Assay: Inhibition of Mer in mouse BaF3 cells
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 534.52, ALogP 3.64, HBA 9, HBD 1, PSA 111.35, QED 0.4
Compound (SMILES): Cc1c(NC(=O)c2ccc(C(C)(C)C)cc2)cccc1-c1ccnc2[nH]c(-c3ccc(C(=O)N4CCOCC4)cc3)nc12
InChIKey: CMNOPGSZOYYDCD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Microfluidic Off-Chip Mobility Shift Assay Protocol for Potency Assessment Against BTK C481S Enzyme: The protocol below describes a microfluidic, off-chip mobility shift kinase assay to measure inherent potency of compounds against BTK C481S enzyme. The mechanics of the assay platform are described by the vendor (PerkinElmer, Hopkinton, Mass.) on their website at the following URL: http://caliperls.com.Briefly, 2.5× stocks of His-TEV-hsBTK(328-659)(C481S) from the Merck Serono Protein Purification Laboratory in Darmstadt, Germany (PCS, Q27/234), 1.6×ATP and appropriate KinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2; Tufts University Core Facility custom synthesis) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM HEPES, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/KinKDR peptide substrate mix were added to Matrix (#4315) 384-well, sterile, flat-bottom polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 25° C. Following the incubation period, reactions were terminated by adding 65 uL quench buffer consisting of 100 mM HEPES, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (PerkinElmer, Mountain View, Calif.), 5% DMSO. Terminated reactions were monitored at −2 PSI, −3000 V/−700 Volts in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was quantified by laser-induced fluorescence measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 573.7, ALogP 6.62, HBA 5, HBD 2, PSA 100.21, QED 0.25
Compound (SMILES): COc1cc(-c2c(C)nn(C)c2C)ccc1-c1nnc(N(C)Cc2ccc3nccn3c2)o1
InChIKey: POLOQBZTXAWWJT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLAG-tagged MER (unknown origin) transfected in Cos-7cells assessed as phosphorylation level incubated for 1 hr by ELISA
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 443.51, ALogP 4.05, HBA 9, HBD 0, PSA 86.51, QED 0.39
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OC/C=C\COc3cccc2c3)cc1OC
InChIKey: QGOZUOJTJYDDMS-LMRHAXCESA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1B (SINGLE PROTEIN), Homo sapiens
UniProt: P68106
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay
Measurement: Kd = 658 nM (pChEMBL 6.179999828338623)
Descriptors: MW 727.9, ALogP 8.01, HBA 9, HBD 0, PSA 101.99, QED 0.17