lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: OESYXUMUXSLZBH-KQBMMHAASA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Displacement of N-Flu-DOT1L from MBP-tagged AF9 (unknown origin) (487 to 568 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 821.07, ALogP 0.68, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3cccc4cccnc34)c12
InChIKey: FDDPCWXTGMYWOD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 435.49, ALogP 5.92, HBA 6, HBD 1, PSA 89.72, QED 0.37
Compound (SMILES): N#Cc1ccccc1Cc1c(Cl)nc2ccnn2c1N1CCC[C@@H](N)C1
InChIKey: VZYIKZNLPOGQBQ-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human DPP4 using A-P-7-amido-4-trifluoromethylcoumarin as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 366.86, ALogP 2.77, HBA 6, HBD 1, PSA 83.24, QED 0.72
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(-c4cnc(N)nc4)c(Cl)n3n2)CC1
InChIKey: IZSUSVHQPBIXPL-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of p110beta/85alpha (unknown origin) using PIP2 as substrate by HTRF assay
Measurement: Ki = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 509, ALogP -0.27, HBA 12, HBD 1, PSA 147.97, QED 0.49
Compound (SMILES): COc1cccc(C(=O)c2ccc3c(ccn3S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)c2)c1
InChIKey: MPHCHZFSBARRJN-DHZHZOJOSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using RHKKAc peptide as substrate
Measurement: IC50 = 323 nM (pChEMBL 6.489999771118164)
Descriptors: MW 476.51, ALogP 3.64, HBA 7, HBD 2, PSA 114.7, QED 0.18
Compound (SMILES): CN(C)C(=O)c1ccc(OCCCCC[C@H]2CC[C@]3(CC2)COC(C)(C)C3)cc1
InChIKey: NOJGRWVDPKFOQU-IHRKKFBRSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 401.59, ALogP 5.7, HBA 3, HBD 0, PSA 38.77, QED 0.52
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(OCC(=O)NCCC4=C5C(C)=CC(C)=[N+]5[B-](F)(F)n5c(C)cc(C)c54)cc3)[nH]c2c1=O
InChIKey: XIMHBHBACDXPTB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from recombinant rat adenosine A2B receptor expressed in CHO cell membranes after 75 mins by liquid scintillation counting method
Measurement: Ki = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 617.47
Compound (SMILES): CC(=O)N1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)C[C@@H]1C
InChIKey: XKTLMQFXVCRIDS-LIRRHRJNSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Human AMCase Activity Assay: An enzymatic assay with recombinant human AMCase was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-Methylumbelliferyl B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of hAMCase recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Buffer (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 55000 nM (pChEMBL 4.260000228881836)
Descriptors: MW 431.97, ALogP 2.17, HBA 6, HBD 2, PSA 94.38, QED 0.77
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3nccc(-c4cc(F)c5nc6n(c5c4)C(C)(C)CC6)n3)nc2)CC1
InChIKey: YPNMKTIHYIVLEE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of recombinant human full length CDK6 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 17.4 nM (pChEMBL 7.760000228881836)
Descriptors: MW 500.63, ALogP 4.59, HBA 8, HBD 1, PSA 75, QED 0.42
Compound (SMILES): COc1ccc(-c2ccccc2)cc1S(=O)(=O)Nc1cccnc1
InChIKey: YJDKKDFKUBEGRD-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Enzyme Kinetic Assay: To determine the inhibition selectivity for inhibitor candidates, human TNAP, PLAP or IAP were added to microtiter plates followed by addition of the substrate pNPP (0.5 mM) and activity was measured in 1 M DEA-HCl buffer, pH 9.8 or in 1 M Tris-HCl buffer, pH 7.5, containing 1 mM MgCl2 and 20 μM ZnCl2, in the presence of potential inhibitors (0-30 μM). TNAP, PLAP and IAP activities were adjusted to an approximate λA405 nm, equivalent to 1, measured after 30 min. Residual AP activity in the presence of inhibitors was expressed as percentage of the control activity. To investigate the mechanism of inhibition, double reciprocal plots of enzyme activity (expressed as mA405 nm min−1) vs. substrate concentration were constructed, in the presence of various concentrations of added inhibitors (0-30 μM). The y-axis intercepts of the 1/v vs. 1/[S] plots, were then plotted vs. [I] to graphically extract Ki values as the x-intercept in this plot. The numerical values from y- and x-intercepts were derived via linear regression analysis, using software Prism 3.02 (GraphPad Software, CA). These analyses were performed, using pNPP as a substrate in 1 M DEA-HCl buffer, pH 9.8, as well as in 1 M Tris-HCl buffer, pH 7.5, to determine Ki at optimal and physiological pH respectively. Inhibitors were further tested and sorted based on their kinetic properties at pH 7.4 using PPi, the relevant natural substrate of TNAP. In this part of the study, pyrophosphate sodium salt (99% ACS reagent, Sigma-Aldrich, St Louis, Mo.) was used as a substrate. Amounts of released phosphate were measured using the Biomol Green Reagent (Biomol Research Laboratories, Inc., Plymouth Meeting, Pa.). Finally, to document the potency of selected inhibitors in physiological media, TNAP inhibition by compounds of Formula I-IV (0-30 μM) was studied at pH 7.4, during catalysis of 0.1 mM pNPP, in the presence of increasing concentrations of Na2HPO4 (0-10 mM) and pyrophosphate (0-40 mM).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 340.4, ALogP 3.56, HBA 4, HBD 1, PSA 68.29, QED 0.77
Compound (SMILES): O=C1/C(=C/c2ccc(OCCCN3CCCCC3)cc2)Cc2cc(OCc3ccc(Br)cc3)ccc21
InChIKey: JJPGVZOMHHYPJU-LGUFXXKBSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected insect cell membranes using kynuramine as substrate after 15 to 20 mins by discontinuous fluorimetric method
Measurement: IC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 546.51, ALogP 7.11, HBA 4, HBD 0, PSA 38.77, QED 0.21
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=[Se])Nc2ccccc2)cc1
InChIKey: OYTLEMICGIEKBU-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 8627 nM (pChEMBL 5.059999942779541)
Descriptors: MW 354.29
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: CDVPARPTSXWSQA-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase-4 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 8654 nM (pChEMBL 5.059999942779541)
Descriptors: MW 478.4, ALogP 4.29, HBA 4, HBD 3, PSA 101.29, QED 0.45
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(P(=O)(O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: FGXIOOMXSBYXDY-RTBURBONSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 553.55, ALogP 2.77, HBA 7, HBD 5, PSA 178.64, QED 0.05
Compound (SMILES): Cl.O=C(O)CCN1CCC2(CC1)COc1cc(OCc3cc(Cl)ccc3Cl)ccc12
InChIKey: UYLWSLDRYJFERA-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay
Measurement: EC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 436.33, ALogP 4.77, HBA 4, HBD 1, PSA 59, QED 0.71
Compound (SMILES): COc1cncc(NC(C(=O)c2c[nH]c3ccccc23)c2ccccc2)c1
InChIKey: FHGKXWSNTAZCCJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 357.41, ALogP 4.61, HBA 4, HBD 2, PSA 67.01, QED 0.49
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1)C(F)(F)F
InChIKey: DMRVMJNKRAGVQH-LBPRGKRZSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Inhibition of recombinant human GlyT1c expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 445.38, ALogP 3.76, HBA 6, HBD 0, PSA 84.04, QED 0.57
Compound (SMILES): CCOc1ccc(-c2c(C#N)c(N)nc(SCC(=O)NC)c2C#N)cc1
InChIKey: CLAMMXDRXFDLCJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as induction of cAMP accumulation by AlphaScreen assay
Measurement: EC50 = 211 nM (pChEMBL 6.679999828338623)
Descriptors: MW 367.43, ALogP 2.31, HBA 7, HBD 2, PSA 124.82, QED 0.75
Compound (SMILES): CC1(C)CCC(C)(C)c2cc(-c3cc(-c4ccc(C(=O)O)cc4)ccc3OCCCCO)ccc21
InChIKey: RGKOTQUMRCWTMY-UHFFFAOYSA-N
Target: Retinoic acid receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10826
Assay: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 472.63, ALogP 7.22, HBA 3, HBD 2, PSA 66.76, QED 0.34
Compound (SMILES): COc1ccc2cc(-c3cn(C[C@H]4NC[C@@H](O)[C@H]4O)nn3)ccc2c1
InChIKey: ZOOUMQYUSBXRNQ-KURKYZTESA-N
Target: Beta-galactosidase (SINGLE PROTEIN), Bos taurus
UniProt: Q58D55
Assay: Inhibition of bovine liver beta-galactosidase using p-nitrophenyl glycopyranoside preincubated for 5 mins followed by substrate addition measured after 20 mins by visible absorption spectroscopic method
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 340.38, ALogP 0.8, HBA 7, HBD 3, PSA 92.43, QED 0.65
Compound (SMILES): Cl.O=S1(=O)CCC(NCCOc2cc(F)ccc2Cl)c2ccccc21
InChIKey: PNVCUCKAMHNRBR-UHFFFAOYSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Displacement of 7-methoxy-[3H]-prazosin from human alpha1D-adrenoreceptor expressed in CHOK1 cell membranes after 60 mins by TopCount liquid scintillation counting method
Measurement: Ki = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 369.85, ALogP 3.37, HBA 4, HBD 1, PSA 55.4, QED 0.82
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1cc(N2CCOCC2)nc(N2CCN(S(C)(=O)=O)CC2)n1
InChIKey: BSBZBFWQLKXCBH-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His-tagged human PI3K p110delta/p85alpha expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 523.57, ALogP 1.68, HBA 10, HBD 0, PSA 105.92, QED 0.48
Compound (SMILES): Cl.O=P(O)(O)OCCN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3Cl)ccc12
InChIKey: LCAOMYPZOURCEH-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay
Measurement: EC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 488.3, ALogP 4.41, HBA 5, HBD 2, PSA 88.46, QED 0.56
Compound (SMILES): CC(C)(C)c1ccc(CC(=O)Nc2ncn(Cc3ccc(F)c(F)c3)n2)cc1
InChIKey: AVPUDFIGAQYICF-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1G (SINGLE PROTEIN), Homo sapiens
UniProt: O43497
Assay: Inhibition of recombinant Cav3.1 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 384.43, ALogP 4.08, HBA 4, HBD 1, PSA 59.81, QED 0.72
Compound (SMILES): COc1ccc2cc(C(C)C(=O)NCCCOc3ccc(S(N)(=O)=O)cc3)ccc2c1
InChIKey: IHKYZJVXRBQNME-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase-4 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 219.8 nM (pChEMBL 6.659999847412109)
Descriptors: MW 442.54, ALogP 3.18, HBA 5, HBD 2, PSA 107.72, QED 0.5
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3cc[n+](Cc4ccccc4F)cc3)ccc12.[Br-]
InChIKey: DMGKKGXQFVPDLI-UHFFFAOYSA-M
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using p-tyramine as substrate after 15 mins by Amplex Red dye-based fluorometric method
Measurement: IC50 = 4210 nM (pChEMBL 5.380000114440918)
Descriptors: MW 376.41, ALogP 4.16, HBA 3, HBD 0, PSA 43.32, QED 0.39
Compound (SMILES): CNC(=O)c1cccc(OCCCCN2CCC(c3noc4cc(F)ccc34)CC2)n1
InChIKey: XDVASEGAPAKNCG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonistic activity at human 5-HT2A receptor assessed as calcium flux after 10 mins by FLIPR assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 426.49, ALogP 3.76, HBA 6, HBD 1, PSA 80.49, QED 0.55
Compound (SMILES): Clc1ccc(-c2nn(Cc3ccccc3)c3c2CCNCC3)cc1
InChIKey: UKJPMZGILXATGT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]5-CT from rat 5-HT7 receptor expressed in HEK293 cell membranes by radioligand binding assay
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 337.85, ALogP 3.94, HBA 3, HBD 1, PSA 29.85, QED 0.78
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(C4CCC(C(=O)NO)CC4)ccc3OCC)nc12
InChIKey: OLKDVNRJRHYWKX-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 = 3110 nM (pChEMBL 5.510000228881836)
Descriptors: MW 453.54, ALogP 3.45, HBA 7, HBD 3, PSA 122.13, QED 0.37
Compound (SMILES): Cc1csc(NC(=O)c2cc(C(F)(F)c3cncnc3)cc3cccnc23)n1
InChIKey: WMANVHZDYKNLDT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 397.41, ALogP 4.18, HBA 6, HBD 1, PSA 80.66, QED 0.56
Compound (SMILES): O=C(CCCCCCC(=O)Nc1ccc(N(CCCl)CCCl)cc1)NO
InChIKey: YKRPYLZHNJSUEJ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human His-tagged HDAC6 expressed in baculovirus infected insect cells preincubated with enzyme followed by flour de lys-green substrate addition measured after 1 hr by fluorescence assay
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 404.34, ALogP 3.76, HBA 4, HBD 3, PSA 81.67, QED 0.2
Compound (SMILES): CCCCNc1nc(N)nc2cccc(OCc3nccc(OC)c3OC)c12
InChIKey: GCJNNJZLCNTFBD-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 383.45, ALogP 3.42, HBA 8, HBD 2, PSA 104.41, QED 0.54
Compound (SMILES): S=C(Nc1ccc2[nH]ccc2c1)Nc1cccc2cnccc12
InChIKey: ZXIUXFLRNUUQPL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human membrane bound MAO-B expressed in insect cell membranes assessed as reduction in conversion of kynuramine to 4-hydroxyquinoline by spectrophotometric assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 318.41, ALogP 4.53, HBA 2, HBD 3, PSA 52.74, QED 0.48
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc([N+](=O)[O-])c2)n1
InChIKey: AIZZLOYYBMQNTD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR in human NCI-H460 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 23570 nM (pChEMBL 4.630000114440918)
Descriptors: MW 470.92, ALogP 4.33, HBA 9, HBD 1, PSA 105.89, QED 0.4
Compound (SMILES): CC(=O)N1c2ccc(-c3cccs3)cc2[C@H](NC(=O)OC(C)C)C[C@@H]1C
InChIKey: CMAUHLPZEGZJFI-SUMWQHHRSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to His-tagged BRD2 bromodomain 1 (unknown origin) by SPR assay
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 372.49, ALogP 4.74, HBA 4, HBD 1, PSA 58.64, QED 0.85
Compound (SMILES): CCCc1cccc(Cl)c1COc1ccc2c(c1)OCC21CCN(CCC(=O)O)CC1.Cl
InChIKey: SQORTZUCYVJUBR-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay
Measurement: EC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 443.97, ALogP 5.07, HBA 4, HBD 1, PSA 59, QED 0.62
Compound (SMILES): Nc1nc2[nH]c(CCC#Cc3cccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)n3)cc2c(=O)[nH]1
InChIKey: XOTHLEQQKQOJFM-HNNXBMFYSA-N
Target: Folate receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P15328
Assay: Binding affinity to human FR-alpha receptor expressed in Chinese hamster RT16 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs in presence of folic acid by Cell-Titer Blue assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 452.43, ALogP 0.26, HBA 7, HBD 6, PSA 204.15, QED 0.26
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCCCCCC[C@](C)(N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: FCGIKWSCRARHTA-JKRYBRSWSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Agonist activity at GFP10/beta-arrestin1-Rluc2 fused human NTS1 expressed in CHO-K1 cell membranes assessed as beta-arrestin1 recruitment after 20 mins by BRET assay
Measurement: EC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 826.09, ALogP 3.34, HBA 9, HBD 8, PSA 246.28, QED 0.11
Compound (SMILES): COc1ccc(Cn2cc(C(=O)NCCCCCCNc3c4c(nc5ccc(OC)cc35)CCCC4)c(=O)c3ccccc32)cc1
InChIKey: XKEZTSHHHMECRM-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human M1 mAChR expressed in CHO cells assessed as inhibition of oxotremorine M-stimulated calcium influx preincubated for 10 mins followed by oxotremorine M addition by Fluo-4 NW dye based fluorescence assay
Measurement: IC50 = 8610 nM (pChEMBL 5.070000171661377)
Descriptors: MW 618.78, ALogP 6.9, HBA 7, HBD 2, PSA 94.48, QED 0.14
Compound (SMILES): NC1=N[C@@]2(c3cc(NC(=O)c4ccc(F)cn4)ccc3F)CCC[C@H]2CS1
InChIKey: UIAVKAKVAXWNHJ-WLRWDXFRSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2 using biotin-GLTNIKTEEISEISYEVEFR-C[Oregon green]KK-OH as substrate after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 42.9 nM (pChEMBL 7.369999885559082)
Descriptors: MW 388.44, ALogP 3.67, HBA 5, HBD 2, PSA 80.37, QED 0.84
Compound (SMILES): CC(C)c1cc2cccc(-c3nnc(C4CCN(CC5CCOCC5)CC4)o3)n2n1
InChIKey: ZFHAKBSSOYHMLY-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate after 12 mins in presence of NADPH-regeneration system by LC-MS/MS method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 409.53, ALogP 4.11, HBA 7, HBD 0, PSA 68.69, QED 0.63
Compound (SMILES): O=c1ccc2cccc(F)c2[nH]1
InChIKey: OGPLOEMLZOLURH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated 15 mins prior to testing by CO2 hydration based stopped-flow assay
Measurement: Ki = 58.8 nM (pChEMBL 7.230000019073486)
Descriptors: MW 163.15, ALogP 1.67, HBA 1, HBD 1, PSA 32.86, QED 0.63
Compound (SMILES): O=C(c1ccc(-c2cccnc2)cc1)N1CCCCc2ccccc21
InChIKey: XITWQTPPESBTKN-UHFFFAOYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of [3H]-AVP from human OXR receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 328.42, ALogP 4.73, HBA 2, HBD 0, PSA 33.2, QED 0.68
Compound (SMILES): O=C(NCc1ccc(N2CCCC2)nc1)c1coc(Cc2ccc(OC(F)(F)F)cc2)n1
InChIKey: GGLRFXACWCOWSX-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1G (SINGLE PROTEIN), Homo sapiens
UniProt: O43497
Assay: Inhibition of recombinant Cav3.1 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 446.43, ALogP 4.09, HBA 6, HBD 1, PSA 80.49, QED 0.59
Compound (SMILES): Cc1cccc(-c2nc(Nc3ccnc4ccccc34)c3cccn3n2)n1
InChIKey: POBTWEXPMBRQFA-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Biological Assays: Assays are conducted in 1536-well plates and 2 mL reactions are prepared from addition of HIS-TGFβR1 T204D or HIS-TGFβR2 WT, anti-HIS detection antibody, a labeled small molecule probe (Kd=<100 nM; koff=<0.001 s−1.) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35, 4 mM DTT, and 0.05 mg/ml BSA). The reaction is incubated for 1 hour at room temperature and the HTRF signal was measured on an Envision plate reader (Ex: 340 nm; Em: 520 nm/495 nm). Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assay are 1 nM HIS-TGFβR1 T204D or HIS-TGFβR2 WT, 0.2 nM anti-HIS detection antibody, labeled small molecule prode (at Kd) and 0.5% DMSO. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 352.4, ALogP 4.39, HBA 6, HBD 1, PSA 68, QED 0.52
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: LEGQBTRPHGOTTN-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28572
Assay: Inhibition of GlyT1 in primary rat cortical neurons assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 479.51, ALogP 4.38, HBA 5, HBD 0, PSA 72.27, QED 0.44
Compound (SMILES): COCCOc1cc2ncnc(N3CCN(c4ncc(Cc5ccccc5)cn4)CC3)c2cc1OCCOC
InChIKey: GWVUCXTYNJIWGK-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Binding affinity to KIT (unknown origin)
Measurement: Kd = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 530.63, ALogP 3.39, HBA 10, HBD 0, PSA 94.96, QED 0.25
Compound (SMILES): CC(=O)NCCN(C)c1cccc(OCCCCCCOc2cccc(OC(=O)NC3CCCCC3)c2)c1
InChIKey: KCUHFUCEFBESAA-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of FAAH1 in Wistar rat brain homogenates using [3H]anandamide as substrate incubated for 30 mins by liquid scintillation counting method
Measurement: IC50 = 197 nM (pChEMBL 6.710000038146973)
Descriptors: MW 525.69, ALogP 5.7, HBA 6, HBD 2, PSA 89.13, QED 0.29
Compound (SMILES): COCCN(C1(C(=O)NO)CN(C(=O)C(C)C)C1)S(=O)(=O)c1ccc(OCc2cc(C)nc3ccccc23)cc1
InChIKey: RASNTKQSEAFGRK-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition Assay: The enzymatic reaction was performed in 384-well microplates with a final volume of 10 ��L containing 1% DMSO. Recombinant Human catalytic domains of MMP1 were assayed with the substrate according to supplier recommendation (ENZO life sciences) and after a preincubation with serial dilutions of tested inhibitors (from 10000 nM to 0.04 nM). After 10 minutes of incubation at room temperature, the fluorescence was measured using a microplate reader (320/425 nm). Data were normalized using the average of positive controls (enzyme with no inhibitor) and negative controls (no enzyme). IC50 were calculated using a four-parameters logistic model.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 570.67, ALogP 2.5, HBA 8, HBD 2, PSA 138.37, QED 0.26
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3Cc3ccc(C(=O)NO)cc3)c2)cc1OC
InChIKey: HQTJYLZBKXSBEN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using RHKKAc peptide as substrate
Measurement: IC50 = 6050 nM (pChEMBL 5.21999979019165)
Descriptors: MW 430.46, ALogP 4.06, HBA 6, HBD 2, PSA 89.79, QED 0.26
Compound (SMILES): COc1cc2c(cc1-c1cnc3ccc(-c4ccnc5[nH]ccc45)cn13)CNC2
InChIKey: IQTLSOGTQGJADC-UHFFFAOYSA-N
Target: Protein kinase C epsilon type (SINGLE PROTEIN), Homo sapiens
UniProt: Q02156
Assay: Inhibition of full-length N-terminal GST-fused human PKC-epsilon expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 381.44, ALogP 4.16, HBA 5, HBD 2, PSA 67.24, QED 0.49
Compound (SMILES): CC(=O)N1CCc2c(c(-c3ccnc4ccccc34)nn2C2CCOCC2)C1
InChIKey: BGBBSIXSMDQYCB-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: TR-FRET Binding Assay: His/Flag epitope tagged CBP was cloned, expressed, and purified to homogeneity. CBP binding and inhibition was assessed by monitoring the engagement of a biotinylated small molecule compound with the target using the TR-FRET assay technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate CBP (4 nM final) was combined with biotin-ligand (60 nM final) in 50 mM HEPES (pH 7.5), 50 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.2% DMSO) or compound dilution series in DMSO. After 10 minutes incubation at room temperature, a mixture Eu-W1024 Anti-6xHis antibody (6xHis is disclosed as SEQ ID NO: 3) (Perkin Elmer ADO 110) and SureLight Allophycocyanin-Streptavidin (APC-SA, Perkin Elmer CR130-100) were added to a final concentrations of 0.2 nMolar antibody and 50 nMolar APC-SA, respectively. After twenty minutes of equilibration, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit.
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 376.46, ALogP 3.35, HBA 5, HBD 0, PSA 60.25, QED 0.69
Compound (SMILES): C[C@H]1C[C@@H](n2c(Nc3ccc(OC(F)(F)F)cc3)nc3cc(CCC(=O)O)ccc32)CC(C)(C)C1
InChIKey: RNMAUIMMNAHKQR-QFBILLFUSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of recombinant wildtype IDH1 (unknown origin) expressed in Escherichia coli BL21(DE3) pLysS cells using DL-isocitrste as substrate assessed as DL-isocitrate conversion to 2OG incubated for 60 mins in presence of NADPH by spectrophotometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 489.54, ALogP 7.08, HBA 5, HBD 2, PSA 76.38, QED 0.37
Compound (SMILES): COc1cc2c(NC3CC4(CCN(C)CC4)C3)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: UDDYBHJZHUMVFR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of Tracer Red binding to human ERG in membranes after 2 hrs by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.7, ALogP 5.96, HBA 7, HBD 1, PSA 63, QED 0.35
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccc(O)cc2)C(N)=O)C(C)C)c1
InChIKey: NKKOQEOUJLZLJY-AOVMBRBZSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 1155.54
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3cc[n+](Cc4cccc(F)c4)cc3)ccc12.[Br-]
InChIKey: UXMYNPRPWZGKKW-UHFFFAOYSA-M
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using p-tyramine as substrate after 15 mins by Amplex Red dye-based fluorometric method
Measurement: IC50 = 2870 nM (pChEMBL 5.539999961853027)
Descriptors: MW 376.41, ALogP 4.16, HBA 3, HBD 0, PSA 43.32, QED 0.39
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc2c(n1)N(C(C)C)[C@H](C)C(=O)N2C
InChIKey: XWNHXTVCPNRSTM-MRXNPFEDSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of BRDT-BD1 (unknown origin) incubated for 1 hr by AlphaScreen biotin-JQ1 competition assay
Measurement: IC50 = 978 nM (pChEMBL 6.010000228881836)
Descriptors: MW 481.6, ALogP 2.63, HBA 8, HBD 2, PSA 102.93, QED 0.65
Compound (SMILES): O=C(CN1CCc2ccccc2C1c1ccccc1)NO
InChIKey: HXOSUHJCHXFHKI-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of recombinant human full-length C-terminal His-tagged HDAC3 (395 to 489 residues)/human NCOR2 expressed in baculovirus infected Sf9 insect cells using Boc-L-Lys(Ac)-AMC as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 282.34, ALogP 2.14, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)C(C)OCC(CS(C)(=O)=O)N3S(C)(=O)=O
InChIKey: KSUXXBLOPRDREE-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 524.59, ALogP 2.87, HBA 7, HBD 1, PSA 122.99, QED 0.54
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN4CCN(C)CC4)C5)ncc3F)cc2n1C(C)C
InChIKey: KZZDDXBCJROTIP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100×, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1×reaction buffer to prepare 5×compound for use; 2 μL 5×compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1×reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1× reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5×enzyme/substrate mixture and 2.5×ATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 80 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50 μM; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 15 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20 μM; 2.5×enzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5×ATP solution, reacted at room temperature for 30 minutes.3. LANCE® Detection Buffer was used, 1× to prepare 2×LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM×10000 was used as the final data for analysis.
Measurement: IC50 = 2.88 nM (pChEMBL 8.539999961853027)
Descriptors: MW 575.67, ALogP 3.93, HBA 9, HBD 1, PSA 95.31, QED 0.37
Compound (SMILES): CCCCC/C=C\[C@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NC1CCC1
InChIKey: QXWVFTRKMJOUAI-HKNKBGDBSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: P47936
Assay: Displacement of [3H]CP-55,940 from mouse CB2 receptor expressed in HEK293 cell membranes in absence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 371.61, ALogP 7.05, HBA 1, HBD 1, PSA 29.1, QED 0.24
Compound (SMILES): COc1cc2c(cc1-c1cnn3ccc(-c4ccnc5[nH]ccc45)cc13)CN(C)C2
InChIKey: DRTOCQUQJDNMBT-UHFFFAOYSA-N
Target: Protein kinase C epsilon type (SINGLE PROTEIN), Homo sapiens
UniProt: Q02156
Assay: Inhibition of full-length N-terminal GST-fused human PKC-epsilon expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 395.47, ALogP 4.5, HBA 5, HBD 1, PSA 58.45, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C)C1CCCCC1
InChIKey: NMCVPEJUMMHCIJ-YADAZJFLSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Displacement of N-Flu-DOT1L from MBP-tagged AF9 (unknown origin) (487 to 568 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 847.11, ALogP 1.21, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): O=S(=O)(Nc1ncns1)c1cc(F)c(OC2OCCNC2c2ccc(Cl)c(Cl)c2)cc1F
InChIKey: HZXKYOMFVBZNGK-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Antagonist activity at recombinant human Nav1.5 expressed in HEK293 cells assessed as reduction in channel current at -50 mV holding potential after 600 secs by barracuda automated electrophysiology method
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 523.37, ALogP 3.99, HBA 8, HBD 2, PSA 102.44, QED 0.5
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CN(Cc3ccccc3)CC(N3CCCC3)C21
InChIKey: QXOWFZHOOCQUMY-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U-69,593 from kappa opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 912 nM (pChEMBL 6.039999961853027)
Descriptors: MW 488.46, ALogP 4.11, HBA 4, HBD 0, PSA 36.02, QED 0.64
Compound (SMILES): Cl.O=C(NCCCN1CCN(C(c2ccccc2)c2ccc(Cl)cc2)CC1)c1ccccn1
InChIKey: YVZBVFNCBJPUOO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08909
Assay: Displacement of [3H]mesulergine from serotonin 5-HT2C receptor in Sprague-Dawley rat brain cortex homogenates incubated for 15 mins by liquid scintillation spectrometry
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 449, ALogP 4.26, HBA 4, HBD 1, PSA 48.47, QED 0.52
Compound (SMILES): Cc1cccc(-n2cc3c(n2)CN(C(=O)c2cc(S(C)(=O)=O)ccc2O[C@@H](C)C(F)(F)F)C3)c1
InChIKey: IAIFDVUVYFIYKI-HNNXBMFYSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28572
Assay: Inhibition of GlyT1 in primary rat cortical neurons assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 493.51, ALogP 4.07, HBA 6, HBD 0, PSA 81.5, QED 0.54
Compound (SMILES): FC(F)(F)CCc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: ZLOMTQBPDHCEQU-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-DOI from recombinant human 5HT2AR transfected in human HEK293 cells incubated for 45 mins by radioligand binding assay
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 285.31, ALogP 2.3, HBA 3, HBD 1, PSA 28.16, QED 0.9
Compound (SMILES): NC(=O)c1cc2ccc(OC(F)(F)F)cc2n1-c1ccnc(CCC(=O)O)c1
InChIKey: YTJFXONMFGIZSP-UHFFFAOYSA-N
Target: Phospholipase A2 group V (SINGLE PROTEIN), Homo sapiens
UniProt: P39877
Assay: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 393.32, ALogP 3.04, HBA 5, HBD 2, PSA 107.44, QED 0.67
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3cc4c(N5CCC(CO)CC5)nc(Nc5ccccc5)nc4cn3)nc2)CC1
InChIKey: LDVFMOHDVNOHBT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR L858R/T790M double mutant (unknown origin) using Poly (Glu, Tyr) as substrate after 40 mins by kinase-Glo luminescence assay
Measurement: IC50 = 44.1 nM (pChEMBL 7.360000133514404)
Descriptors: MW 553.72, ALogP 4.65, HBA 10, HBD 3, PSA 105.57, QED 0.29
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: YCYOWXTYVQGGHS-XKGNXMRFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Binding affinity to recombinant human flag/His-tagged IL-23R (1 to 353 residues) expressed in HEK293F cells assessed as disruption of biotinylated IL-23 binding to receptor preincubated for 1 hr followed by biotinylated IL-23 addition measured after over night incubation by AlphaLISA assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 1623.82
Compound (SMILES): CCC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)nc2N1C1CCCC1
InChIKey: ZUJOXCIHOKDDRE-HSZRJFAPSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of BRDT-BD1 (unknown origin) incubated for 1 hr by AlphaScreen biotin-JQ1 competition assay
Measurement: IC50 = 8468 nM (pChEMBL 5.070000171661377)
Descriptors: MW 535.69, ALogP 3.95, HBA 8, HBD 2, PSA 102.93, QED 0.52
Compound (SMILES): Cc1cc(-c2cccc(-c3c(C(=O)O)noc3-c3ccccc3)c2)cc(C)c1O
InChIKey: YJWODEWDNRBMBA-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB R136A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 385.42, ALogP 5.7, HBA 4, HBD 2, PSA 83.56, QED 0.47
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC1=O
InChIKey: FNFABWIIQJFQLF-IVXOOQPNSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method
Measurement: Kd = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 1564.84
Compound (SMILES): CC1(COc2ccc(CC(=O)Nc3ccn(Cc4ccc(F)c(F)c4)n3)cc2)COC1
InChIKey: ITUMLSDPGXHKCM-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1G (SINGLE PROTEIN), Homo sapiens
UniProt: O43497
Assay: Inhibition of recombinant Cav3.1 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 427.45, ALogP 3.81, HBA 5, HBD 1, PSA 65.38, QED 0.59
Compound (SMILES): N[C@H]1CCN(Cc2ccn3nc(-c4ccccn4)nc(Nc4ccncc4F)c23)C[C@@H]1O
InChIKey: HUEXJRRSSHIGFJ-LPHOPBHVSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Biological Assays: Assays are conducted in 1536-well plates and 2 mL reactions are prepared from addition of HIS-TGFβR1 T204D or HIS-TGFβR2 WT, anti-HIS detection antibody, a labeled small molecule probe (Kd=<100 nM; koff=<0.001 s−1.) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35, 4 mM DTT, and 0.05 mg/ml BSA). The reaction is incubated for 1 hour at room temperature and the HTRF signal was measured on an Envision plate reader (Ex: 340 nm; Em: 520 nm/495 nm). Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assay are 1 nM HIS-TGFβR1 T204D or HIS-TGFβR2 WT, 0.2 nM anti-HIS detection antibody, labeled small molecule probe (at Kd) and 0.5% DMSO. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 434.48, ALogP 1.96, HBA 9, HBD 3, PSA 117.49, QED 0.44
Compound (SMILES): Cc1ccn(-c2ccc(C(=O)N3CCCCc4ccccc43)cc2)n1
InChIKey: UVTTVOUSHGWOND-UHFFFAOYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of [3H]-AVP from human OXR receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 331.42, ALogP 4.16, HBA 3, HBD 0, PSA 38.13, QED 0.71
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)cc2)cc1-c1ccc2c(c1)C(C)(C)CCC2(C)C
InChIKey: HBNBYJCDYSPKDL-UHFFFAOYSA-N
Target: Retinoic acid receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10826
Assay: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 414.55, ALogP 7.08, HBA 2, HBD 1, PSA 46.53, QED 0.5
Compound (SMILES): COc1ccc(-c2ccc(S(=O)(=O)c3ccccc3C(=O)CS(C)(=O)=O)cc2)cc1
InChIKey: SLZVJQPKZGCZCI-UHFFFAOYSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of recombinant human MMP-12 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition measured every 10 secs for 15 mins by fluorometric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.53, ALogP 3.42, HBA 6, HBD 0, PSA 94.58, QED 0.52
Compound (SMILES): COC(=O)Cc1ccc(OC[C@H](O)CN2CCN(c3cc(C)ccc3C)CC2)cc1
InChIKey: OANREMIQEOYENB-OAQYLSRUSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23944
Assay: Antagonist activity at alpha1D-adrenoreceptor in Sprague-Dawley rat thoracic aorta assessed as relaxation of (-)-noradrenaline-induced contractile response
Measurement: Kd = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 412.53, ALogP 2.58, HBA 6, HBD 1, PSA 62.24, QED 0.67
Compound (SMILES): Cn1c(C#N)c2c(c1C(=O)NCc1cccnc1OCC(F)(F)F)CCC(C)(C)C2
InChIKey: FGOMAEMCCGRKRQ-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of recombinant human Cav3.3 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 420.44, ALogP 3.68, HBA 5, HBD 1, PSA 79.94, QED 0.8
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2-c2ccc(C3(C#N)CC3)cc2)CC1
InChIKey: WIXZFNIBMHEUJH-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Stabilization of ALDH1A1 in human OV90 cells assessed as increase in melting temperature at 70 degC after 1 hr by CETSA
Measurement: EC50 = 5590 nM (pChEMBL 5.25)
Descriptors: MW 478.55, ALogP 3.31, HBA 5, HBD 0, PSA 94.37, QED 0.57
Compound (SMILES): COc1cc(/C=C/c2ccc(OS(=O)(=O)C3CC4OC3C(c3ccc(O)cc3)=C4c3ccc(O)cc3)cc2)cc(OC)c1
InChIKey: XHKLZVBLMBBATN-ONEGZZNKSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at human ERbeta expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 598.67, ALogP 6.14, HBA 8, HBD 2, PSA 111.52, QED 0.17
Compound (SMILES): CN1CCN(c2ccc(Nc3cc4c(N5CCOCC5)nc(Nc5ccccc5)nc4cn3)nc2)CC1
InChIKey: NZHWCKUCRNYHBJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR L858R/T790M double mutant (unknown origin) using Poly (Glu, Tyr) as substrate after 40 mins by kinase-Glo luminescence assay
Measurement: IC50 = 53.2 nM (pChEMBL 7.269999980926514)
Descriptors: MW 497.61, ALogP 3.5, HBA 10, HBD 2, PSA 94.57, QED 0.41