lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C#CCCCCN1CCC(c2ccc(-c3cc(C(=O)O)cc4cc(-c5ccc(C(F)(F)F)cc5)ccc34)cc2)CC1
InChIKey: XNUCWDPJVQRZKC-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Mus musculus
UniProt: Q9ESG6
Assay: Inhibition of MRS4174 binding to mouse P2Y14R expressed in HEK293 cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 555.64, ALogP 8.87, HBA 2, HBD 1, PSA 40.54, QED 0.17
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(C(O)c4ccc(C(=O)NO)cc4)ccc3OCC)nc12
InChIKey: IUQUWTOVRNIGDN-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 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 477.52, ALogP 2.88, HBA 8, HBD 4, PSA 142.36, QED 0.23
Compound (SMILES): O=S(=O)(Oc1ccccc1Cl)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: CQDCBCLWITTXGG-AATRIKPKSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at human ERalpha expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: EC50 = 273 nM (pChEMBL 6.559999942779541)
Descriptors: MW 589.07, ALogP 6.49, HBA 7, HBD 3, PSA 113.29, QED 0.17
Compound (SMILES): CC(C)c1cc2c(cc1S(=O)(=O)N[C@H](Cc1ccccc1)C(=O)Nc1ccccc1F)[C@@]1(C)CCC[C@@](C)(C(=O)N[C@H](Cc3ccccc3)C(=O)Nc3ccccc3F)[C@@H]1CC2
InChIKey: KTGRBNDUSNDAMR-BEFHDJFHSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 (Ala20 to Asp707 residues) expressed in CHO cells using Mca-Pro-LeuGly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 66600 nM (pChEMBL 4.179999828338623)
Descriptors: MW 861.07, ALogP 8.99, HBA 5, HBD 4, PSA 133.47, QED 0.09
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)CO)n1
InChIKey: BQBNPQXFWWIVER-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 = 2010 nM (pChEMBL 5.699999809265137)
Descriptors: MW 498.97, ALogP 3.36, HBA 9, HBD 3, PSA 112.08, QED 0.43
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cccc(O)c2)c1
InChIKey: HDBQZCCNZOGXEE-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB E129A 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 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 357.37, ALogP 5.08, HBA 4, HBD 2, PSA 83.56, QED 0.53
Compound (SMILES): CCC(SC1=Nc2ccccc2C2=NC(C(C)CC)C(=O)N12)C(=O)Nc1ccccc1C
InChIKey: HTFJGDBBWXQQCN-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 after 1 hr by CETSA
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 448.59, ALogP 5.15, HBA 5, HBD 1, PSA 74.13, QED 0.66
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N1CCCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
InChIKey: VDGMDLWYOUANBX-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at GAL4-tagged human LXRalpha assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 457.37, ALogP 4.28, HBA 3, HBD 1, PSA 57.61, QED 0.7
Compound (SMILES): CC1(C)CCSc2ccc(C#Cc3cccc(C(=O)O)n3)cc21
InChIKey: GTCFCUSLARKKEK-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 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 323.42, ALogP 3.95, HBA 3, HBD 1, PSA 50.19, QED 0.81
Compound (SMILES): Cl.Cl.FCCOc1ccccc1CCN1CCN(CCc2ccccc2)CC1
InChIKey: ZMAVQUKGEDDCHL-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]dopamine uptake at VMAT2 in rat striatal synaptic vesicles by scintillation spectrometry
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 356.49, ALogP 3.44, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): NC(=O)c1ccc(-c2cn3c(-c4ccc(O)cc4)cnc3cn2)cc1
InChIKey: LKFLRBIQIXBCCO-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of GST-tagged MNK2 (72 to 385 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 330.35, ALogP 2.87, HBA 5, HBD 2, PSA 93.51, QED 0.6
Compound (SMILES): COc1ccccc1CCN1CCC(CCc2ccccc2OCCF)CC1.Cl
InChIKey: YFHDJRXKUBGRGA-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Inhibition of [3H]dopamine uptake at dopamine transporter in rat striatal synaptosomes preincubated for 5 mins followed by radioligand addition measured after 10 mins by scintillation spectrometry
Measurement: Ki = 2310 nM (pChEMBL 5.639999866485596)
Descriptors: MW 385.52, ALogP 4.93, HBA 3, HBD 0, PSA 21.7, QED 0.58
Compound (SMILES): O=c1ccc2ccccc2[te]1
InChIKey: XKISACYHJSOTET-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 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 257.75
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCCCOc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: UBWFOFQYWMLOHJ-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 = 63.7 nM (pChEMBL 7.199999809265137)
Descriptors: MW 418.56, ALogP 3.22, HBA 4, HBD 2, PSA 98.49, QED 0.58
Compound (SMILES): CCOc1cc(=O)[nH]cc1-c1ccc(CC(=O)Nc2cc(-c3nnc(C)o3)cc(C(F)(F)F)c2)c(F)c1
InChIKey: QGWFBTCMBJQAGH-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET phosphorylation in human TT cells after 2 hrs by ELISA
Measurement: IC50 = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 516.45, ALogP 5.14, HBA 6, HBD 2, PSA 110.11, QED 0.33
Compound (SMILES): CCOC(=O)c1c(C)oc2cc(OCc3ccccc3)c(OCc3oc4cc(OCC5CCCCC5)c(OS(=O)(=O)[O-])cc4c3C(=O)OCC)cc12.[Na+]
InChIKey: RVIRXUKDYXNKEW-UHFFFAOYSA-M
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using spectrozyme TH as substrate pretreated for 10 mins followed by substrate addition measured in absence of exosite 1 competitor hirudine peptide by spectrophotometric method
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 736.79, ALogP 8.14, HBA 12, HBD 1, PSA 170.17, QED 0.08
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-n3cnc4ccccc43)c12
InChIKey: XAHJWGOHTQLOMU-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 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 410.44, ALogP 4.73, HBA 7, HBD 1, PSA 94.65, QED 0.45
Compound (SMILES): COC(=O)Cc1ccc(OCC(O)CN2CCN(c3cc(C)ccc3C)CC2)cc1
InChIKey: OANREMIQEOYENB-UHFFFAOYSA-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 = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 412.53, ALogP 2.58, HBA 6, HBD 1, PSA 62.24, QED 0.67
Compound (SMILES): CC(C)(CO)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cn3)c2)c2cnc(N)nc21
InChIKey: BPIWZDNVMQQBQX-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of human TrkC expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 479.93, ALogP 2.6, HBA 9, HBD 3, PSA 148.91, QED 0.34
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN(C)C)C5)ncc3F)cc2n1C(C)C
InChIKey: SSVSKCKWUAPYHI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: LANCE Ultra ULight 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 100x, 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 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE 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 x10000 was used as the final data for analysis.
Measurement: IC50 = 33.7 nM (pChEMBL 7.46999979019165)
Descriptors: MW 520.59, ALogP 4.25, HBA 8, HBD 1, PSA 92.07, QED 0.41
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)CC6)n3)nc2)CC1
InChIKey: YCANTYAOGZQCIG-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 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 504.59, ALogP 4.55, HBA 8, HBD 1, PSA 75, QED 0.41
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2C(=O)N(c2cccc(F)c2)[C@@]2(C(=O)NC3CC(F)(F)C3)CCc3cc(Cl)ccc32)c1
InChIKey: BZJCZDVCLIWRFK-FKAPRUDGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 (unknown origin) using isocitrate as substrate after 60 mins by resazurin dye based fluorescence assay
Measurement: IC50 = 1780 nM (pChEMBL 5.75)
Descriptors: MW 608.02, ALogP 5.03, HBA 5, HBD 1, PSA 106.4, QED 0.42
Compound (SMILES): NCCCCNc1nc(Nc2ccc(CN3CCOCC3)cc2)c2ncn(C3CCCC3)c2n1
InChIKey: SBLIKFBWCULFJM-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST/His6-fused recombinant human FLT3 (R571 to S993 residues) D835Y mutant expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 464.62, ALogP 3.67, HBA 9, HBD 3, PSA 106.15, QED 0.39
Compound (SMILES): CCOc1ccccc1N1CCN(CCNC(=O)c2ccccn2)CC1
InChIKey: MGEBVTZNSCZOCM-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 354.45, ALogP 2.03, HBA 5, HBD 1, PSA 57.7, QED 0.82
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CNCC(N3CCCC3)C21
InChIKey: JMSHYBARLFGBPR-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P97266
Assay: Displacement of [3H]DAMGO from mu opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 398.33, ALogP 2.2, HBA 4, HBD 1, PSA 44.81, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(OCCNC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: VNIROKIVWRXGRV-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 = 5483 nM (pChEMBL 5.260000228881836)
Descriptors: MW 494.4, ALogP 4.12, HBA 5, HBD 3, PSA 110.52, QED 0.39
Compound (SMILES): CCC1(OC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)C[C@@H]2CCNC2=O)CCN(C(=O)OC(C)(C)C)CC1
InChIKey: HTGYFQGYLZPRLD-UFYCRDLUSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Feline coronavirus (strain FIPV WSU-79/1146) (FCoV)
UniProt: Q98VG9
Assay: Inhibition of Feline infectious peritonitis virus 3CL protease using Dabcyl-KTSAVLQ/SGFRKME-Edans as substrate incubated for 30 mins followed by substrate addition measured after 1 hr by FRET assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 524.66, ALogP 2.52, HBA 7, HBD 3, PSA 143.14, QED 0.37
Compound (SMILES): O=C(NC1CC1)c1cc(OCCCCN2CCC(c3noc4cc(F)ccc34)CC2)ccn1
InChIKey: MGMRTFVVFOMBEF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonistic activity at human 5-HT1A receptor measured after 60 mins by Ultra Lance cAMP assay
Measurement: EC50 = 28.1 nM (pChEMBL 7.550000190734863)
Descriptors: MW 452.53, ALogP 4.29, HBA 6, HBD 1, PSA 80.49, QED 0.49
Compound (SMILES): COc1cc(C)ccc1S(=O)(=O)Nc1cccnc1
InChIKey: LZWDXCJPPLHLQH-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 < 100 nM (pChEMBL 7)
Descriptors: MW 278.33, ALogP 2.2, HBA 4, HBD 1, PSA 68.29, QED 0.93
Compound (SMILES): CC1(C)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: QEQUHVRIJFFOKD-LMOJIFKQSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins
Measurement: EC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 875.99, ALogP -0.46, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1ccc(-c2ccccc2)cc1
InChIKey: FHKFHTMCQMFFEY-AOYPEHQESA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q05940
Assay: Displacement of [3H](+)-syn-Ethyl 1-(2-(2,4-Dioxo-1,2-dihydroquinazolin-3(4H)-yl)ethyl)-4-(4-fluorophenyl)piperidine-3-carboxylate from human VMAT2 expressed in HEK293 cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki = 3770 nM (pChEMBL 5.420000076293945)
Descriptors: MW 497.6, ALogP 4.03, HBA 6, HBD 1, PSA 84.4, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-n3ccnc3)c12
InChIKey: RIDMLRBIZLZHIF-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 = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 360.38, ALogP 3.58, HBA 7, HBD 1, PSA 94.65, QED 0.53
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cscn2)c1)c1ccccc1
InChIKey: UTRPLZGACFVGID-FCHUYYIVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of dexamethasone induced transactivation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 470.55, ALogP 5.4, HBA 6, HBD 1, PSA 69.04, QED 0.37
Compound (SMILES): CCc1nn2c(C)cc(C)nc2c1Cc1ccc(CCC(=O)N2CCNCC2)cc1
InChIKey: NACVEUIUKZPVQS-UHFFFAOYSA-N
Target: G-prodeshotein coupled receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P46093
Assay: Antagonist activity at human GPR4 expressed in human HeLa cells assessed as inhibition of IBMX-induced cAMP accumulation after 15 mins by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 405.55, ALogP 2.86, HBA 5, HBD 1, PSA 62.53, QED 0.69
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(-n2cc(-c3cncnc3)c3nc(N(C)C4CCN(CC)CC4)ccc32)c1F
InChIKey: AEJACXAFHXBVHF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation after 2 hrs by ELISA
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 569.68, ALogP 4.83, HBA 8, HBD 1, PSA 96.25, QED 0.31
Compound (SMILES): Cc1ncncc1-c1cc(Cl)cc2c1nc(N1CC3(CNC3)C1)n2Cc1ccc(F)cc1
InChIKey: AYHMANSGNZEDBM-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Activation of SOS1 in human NCI-H727 cells expressing KRAS G12V mutant assessed as induction of ERK1/2 T202/Y204 phosphorylation incubated for 30 mins by In-cell Western assay
Measurement: EC50 = 42500 nM (pChEMBL 4.369999885559082)
Descriptors: MW 448.93, ALogP 4.05, HBA 6, HBD 1, PSA 58.87, QED 0.51
Compound (SMILES): NCCCNC(=O)c1ccc(-c2cc(C(=O)O)cc(-n3cc(-c4ccc(C(F)(F)F)cc4)nn3)c2)s1
InChIKey: VYXSDIPOJBFWHQ-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Mus musculus
UniProt: Q9ESG6
Assay: Inhibition of MRS4174 binding to mouse P2Y14R expressed in HEK293 cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 384 nM (pChEMBL 6.420000076293945)
Descriptors: MW 515.52, ALogP 4.46, HBA 7, HBD 3, PSA 123.13, QED 0.3
Compound (SMILES): COc1cccc(/C=C/C(=O)c2ccncc2)c1
InChIKey: SMEDYRIIZMHYEO-AATRIKPKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in yeast microsomal membranes using dibenzylfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 239.27, ALogP 2.99, HBA 3, HBD 0, PSA 39.19, QED 0.61
Compound (SMILES): COC(=O)c1cc(-c2cn(C(C)C)c3ccccc23)n[nH]1
InChIKey: TUZFGQFWBUTVGZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 catalytic domain preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7360 nM (pChEMBL 5.130000114440918)
Descriptors: MW 283.33, ALogP 3.4, HBA 4, HBD 1, PSA 59.91, QED 0.75
Compound (SMILES): Cn1c(Cl)c2c(c1C(=O)NCc1ccccc1OCC(F)(F)F)CCC(C)(C)C2
InChIKey: OWTDJGCKDWJAIU-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 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 428.88, ALogP 5.06, HBA 3, HBD 1, PSA 43.26, QED 0.72
Compound (SMILES): O=C(CCCCCCN(Cc1ccccc1)Cc1ccccc1)NO
InChIKey: DTZPKSVXYRJCGJ-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 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 340.47, ALogP 4.14, HBA 3, HBD 2, PSA 52.57, QED 0.37
Compound (SMILES): CN(Cc1ccccc1OCCCCC(C)(C)C(=O)O)C(=O)c1ccc(-c2ccco2)cc1
InChIKey: RDTZXAYSBVNVKN-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Activation of human PPARalpha LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.55, ALogP 5.88, HBA 4, HBD 1, PSA 79.98, QED 0.37
Compound (SMILES): CC(C)[C@@H]1N=C(c2ccccc2F)c2cc(Cl)ccc2NC1=S
InChIKey: IIYOCBNZOLLZCM-INIZCTEOSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Positive allosteric modulation of M5 receptor (unknown origin)
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 346.86, ALogP 5.09, HBA 2, HBD 1, PSA 24.39, QED 0.77
Compound (SMILES): CC1(C)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: YSZTVMQFORZYJG-LUKCZKMGSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 839.96, ALogP -1.22, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): O=C1C(c2ccccc2)N(S(=O)(=O)c2ccc(Br)cc2)C(=O)C(c2ccccc2)N1S(=O)(=O)c1ccc(Br)cc1
InChIKey: PFDDVBQKOQRERD-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH as substrate preincubated for 60 mins followed by substrate addition by fluorescence analysis
Measurement: IC50 = 32.71 nM (pChEMBL 7.489999771118164)
Descriptors: MW 704.42, ALogP 5.44, HBA 6, HBD 0, PSA 108.9, QED 0.26
Compound (SMILES): C[C@@](O)(C/C=C/[C@H]1CCC(=O)[C@@H]1CCSc1nc(C(=O)O)cs1)CCC(F)(F)F
InChIKey: WQXORXCPXXDTAR-CMPKWODGSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at recombinant human EP2 receptor expressed in CHO cells assessed as increase in intracellular cAMP level by EIA
Measurement: EC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 451.53, ALogP 4.96, HBA 6, HBD 2, PSA 87.49, QED 0.39
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]nc(-c4ccncc4)c3c2)cnc1Cl)c1ccccc1
InChIKey: JNQFWBSHMGXTQX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 1.17 nM (pChEMBL 8.930000305175781)
Descriptors: MW 462.92, ALogP 4.54, HBA 6, HBD 2, PSA 113.52, QED 0.37
Compound (SMILES): O=C(Nc1ccn(Cc2ccccc2)n1)c1ccccc1
InChIKey: CSTXSHCPJGEVDX-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 277.33, ALogP 3.18, HBA 3, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): O=C(CSc1nc2c(c(=O)n1Cc1ccccc1)SCC2)Nc1nc2ccc(C(F)(F)F)cc2s1
InChIKey: AKDORUDVYNLYEP-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q06486
Assay: Inhibition of rat GST-tagged CK1delta M82F mutant at 10 uM using alpha-casein as substrate after 30 mins in presence of [gamma-32P]-ATP by Cherenkov counting method
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 534.61, ALogP 5.3, HBA 8, HBD 1, PSA 76.88, QED 0.27
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCN(S(C)(=O)=O)CC2)n1
InChIKey: ONOXYKBOLXDGLJ-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 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 524.55, ALogP 1.07, HBA 11, HBD 0, PSA 118.81, QED 0.46
Compound (SMILES): Cc1cc(OCCCN2CCN(c3ccccc3)CC2)ccc1Cl.Cl.Cl
InChIKey: RTHQQMXOILOELC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 344.89, ALogP 4.24, HBA 3, HBD 0, PSA 15.71, QED 0.73
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2ccccn12)c1ccc(Cl)cc1
InChIKey: AZKMWHRDICVYEI-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P63079
Assay: Modulation of rat eGFP-fused GABA-A receptor alpha6beta3 expressed in HEK293 cells in presence of GABA by patch-clamp assay
Measurement: EC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 353.83, ALogP 4.97, HBA 4, HBD 1, PSA 46.4, QED 0.56
Compound (SMILES): Fc1ccc(Cc2ccnc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: PUZQIEAXLJCDIM-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 2.15 nM (pChEMBL 8.670000076293945)
Descriptors: MW 297.38, ALogP 2.54, HBA 3, HBD 1, PSA 28.16, QED 0.92
Compound (SMILES): CN(Cc1ccccc1OCCC/C=C/C(=O)O)C(=O)c1ccc(-c2ccco2)cc1
InChIKey: PRLUQZAEJIZRCO-QDEBKDIKSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human PPARgamma LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.48, ALogP 5.02, HBA 4, HBD 1, PSA 79.98, QED 0.37
Compound (SMILES): O=C(O)CCC(=O)N(C1CC1)[C@H]1c2ccc(Cl)cc2N(C(=O)c2ccc(OC(F)(F)F)cc2)[C@H]2CCC[C@H]21
InChIKey: VXPZDNJSQWTDNN-FZOAFFARSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity at human CRTh2 expressed in CHOK1 cells assessed as inhibition of PGD2-induced beta-arrestin recruitment incubated for 30 mins followed by PGD2 stimulation measured after 60 mins by PathHunter based chemiluminescence assay
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 550.96, ALogP 5.96, HBA 4, HBD 1, PSA 87.15, QED 0.46
Compound (SMILES): O=C1C(c2ccccc2)N(S(=O)(=O)c2ccc([N+](=O)[O-])cc2)C(=O)C(c2ccccc2)N1S(=O)(=O)c1ccc([N+](=O)[O-])cc1
InChIKey: JREVZBFUZBCAHI-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH as substrate preincubated for 60 mins followed by substrate addition by fluorescence analysis
Measurement: IC50 = 33.47 nM (pChEMBL 7.46999979019165)
Descriptors: MW 636.62, ALogP 3.73, HBA 10, HBD 0, PSA 195.18, QED 0.2
Compound (SMILES): CCc1cccc(-c2c(F)cccc2C(O)(CCCNC(=O)OC)[C@@H]2CCCN(C(=O)CC(O)CNC)C2)c1
InChIKey: FWSYQZYECHPKKP-QFYHAUMRSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in Escherichia coli co-expressing CYP-reductase using diethoxyfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 543.68, ALogP 3.59, HBA 6, HBD 4, PSA 111.13, QED 0.3
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(CC(=O)NO)cc4)ccc3OCC)nc12
InChIKey: AFVWNFJXGSIJSF-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of full length human recombinant C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 (95 to 489 residues) expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 475.55, ALogP 3.31, HBA 7, HBD 3, PSA 122.13, QED 0.25
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2ccc(O)cc2)c1
InChIKey: QSBOZQWNPQOIPA-UHFFFAOYSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB 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 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 357.37, ALogP 5.08, HBA 4, HBD 2, PSA 83.56, QED 0.53
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3cc4c(N5CCCC5)nc(Nc5ccccc5)nc4cn3)nc2)CC1
InChIKey: LGMJCNIZSXOQFC-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 = 65.6 nM (pChEMBL 7.179999828338623)
Descriptors: MW 509.66, ALogP 5.04, HBA 9, HBD 2, PSA 85.34, QED 0.36
Compound (SMILES): Cc1ccc(Cn2c(N3CCNCC3)cc(=O)n3nccc23)cc1
InChIKey: ZEXSKJJPYRSRAY-UHFFFAOYSA-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 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 323.4, ALogP 1.26, HBA 6, HBD 1, PSA 54.57, QED 0.79
Compound (SMILES): CCc1ccc(-c2cc(NCC3CCN(C)CC3)c3cc(OC)c(OCCCN4CCCC4)cc3n2)o1
InChIKey: PQJVPCANHLGIOZ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of GLP (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 506.69, ALogP 5.68, HBA 7, HBD 1, PSA 63, QED 0.34
Compound (SMILES): CN(C)C[C@H]1C2CCC(c3ccccc3)(C2)[C@H]1O
InChIKey: HGNFUCJMHJYHIN-ZTTSNEECSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Binding affinity to 6His-tagged and human KDM4C tandem TUDOR domain (874 to 990 residues) expressed in Escherichia coli BL21(DE3)-T1R by ITC method
Measurement: Kd = 129000 nM (pChEMBL 3.890000104904175)
Descriptors: MW 245.37, ALogP 2.28, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O
InChIKey: VPDBSKOWEPRFMT-DZCXQCEKSA-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 > 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 1366.62
Compound (SMILES): COC(=O)CNC(=O)NCc1ccc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)cc1C
InChIKey: XOYDUGXEXIVUAJ-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of DY647 from SNAP-tagged V2 receptor (unknown origin) expressed in HEK293 cells by TR-FRET assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 462.51, ALogP 2.6, HBA 7, HBD 3, PSA 117.59, QED 0.5
Compound (SMILES): COc1cc2c(cc1-n1cnc3ccc(-c4ccnc5[nH]ccc45)nc31)CNC2
InChIKey: VKQMYKOSLRYFTF-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 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 382.43, ALogP 3.58, HBA 6, HBD 2, PSA 80.65, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=[Se])Nc2ccc(F)cc2)cc1
InChIKey: WEUISFFZQUMPMK-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 = 7557 nM (pChEMBL 5.119999885559082)
Descriptors: MW 372.28
Compound (SMILES): CC(C)C[C@H]1CN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)CN1C
InChIKey: RCGRIXXPKNDBJW-SFTDATJTSA-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 < 100 nM (pChEMBL 7)
Descriptors: MW 446.04, ALogP 3.28, HBA 6, HBD 2, PSA 77.31, QED 0.71
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](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: UZHRVXRQUPFWLS-RPXHOIECSA-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 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 855.09, ALogP 0.87, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4cnc(N)nc4)c(Cl)n3n2)CC1
InChIKey: NOCRVEDBMWCMTR-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 = 71.9 nM (pChEMBL 7.139999866485596)
Descriptors: MW 508.01, ALogP 0.34, HBA 11, HBD 1, PSA 135.08, QED 0.51
Compound (SMILES): CC(C)(O)[C@H](F)CNC(=O)C[C@@H]1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: FQWMGYJHFABALZ-FXAWDEMLSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at GAL4-tagged human LXRalpha assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 618.54, ALogP 4.26, HBA 5, HBD 3, PSA 106.94, QED 0.38
Compound (SMILES): O=S(=O)(Oc1ccccc1)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: ZAZMBTKOZBHDGU-VOTSOKGWSA-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 = 658 nM (pChEMBL 6.179999828338623)
Descriptors: MW 554.62, ALogP 5.83, HBA 7, HBD 3, PSA 113.29, QED 0.19
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N1CCOc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
InChIKey: REOZCXVKAAJOFL-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 459.34, ALogP 3.73, HBA 4, HBD 1, PSA 66.84, QED 0.71
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)nc3)nn(CC3CCCC3)c2n1
InChIKey: MMJWZGGVKOHMPQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of wild-type human partial length MTOR (L1382 to W2549 residues) expressed in mammalian expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 392.51, ALogP 2.53, HBA 8, HBD 2, PSA 83.79, QED 0.69
Compound (SMILES): Cc1cc(Cn2c(N3CC4(CNC4)C3)nc3c(N4CCN(C)CC4)cc(Cl)cc32)cc(C)c1F
InChIKey: JWZAQUXBYYOGFA-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Activation of SOS1 in human NCI-H727 cells expressing KRAS G12V mutant assessed as induction of ERK1/2 T202/Y204 phosphorylation incubated for 30 mins by In-cell Western assay
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 483.04, ALogP 3.66, HBA 6, HBD 1, PSA 39.57, QED 0.61
Compound (SMILES): c1ccc2c(NCCCCC[Se]CCCCCNc3c4c(nc5ccccc35)CCCC4)c3c(nc2c1)CCCC3
InChIKey: RFJOKGIIFYOSLX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Mixed-type inhibition of equine serum BuChE assessed as enzyme-inhibitor complex using p-nitrophenyl butyrate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 613.75
Compound (SMILES): COc1cccc(Cn2c(SCC(=O)Nc3nc4ccc(C(F)(F)F)cc4s3)nc3c(c2=O)SCC3)c1OC
InChIKey: ASNBCMDJKIZLOU-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q06486
Assay: Inhibition of rat GST-tagged CK1delta M82F mutant at 10 uM using alpha-casein as substrate after 30 mins in presence of [gamma-32P]-ATP by Cherenkov counting method
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 594.66, ALogP 5.32, HBA 10, HBD 1, PSA 95.34, QED 0.22
Compound (SMILES): C=CC(=O)Nc1ccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ncc2Cl)cc1
InChIKey: JPEBHFDPUUEBJJ-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 = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 494.98, ALogP 4.55, HBA 8, HBD 2, PSA 91.85, QED 0.44
Compound (SMILES): NC(=O)c1cc2ccc(OC(F)(F)F)cc2n1-c1cc(CCC(=O)O)ccn1
InChIKey: KEQSTBYHFUWBLB-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 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 393.32, ALogP 3.04, HBA 5, HBD 2, PSA 107.44, QED 0.67
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](Cc2ccc(C#Cc3ccccc3)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)O
InChIKey: LWPABDJNWSXGPM-HZWOCANUSA-N
Target: Urotensin-2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKP6
Assay: Displacement of [Na125I]-synthetic URP from human UT receptor expressed in HEK293 cell membranes incubated for 2 hrs by gamma-counting
Measurement: IC50 = 26.92 nM (pChEMBL 7.570000171661377)
Descriptors: MW 1117.36
Compound (SMILES): NCCCCCNc1nc(Nc2ccc(CN3CCOCC3)cc2)c2ncn(C3CCCC3)c2n1
InChIKey: UDOUBBQTHDACPD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST/His6-fused recombinant human FLT3 (R571 to S993 residues) D835Y mutant expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 478.65, ALogP 4.06, HBA 9, HBD 3, PSA 106.15, QED 0.35
Compound (SMILES): CCC1Cc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(CC)CC6)cn5)ncc4F)cc3n2C1
InChIKey: UGRAFLUUHGUBAR-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 = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 518.62, ALogP 4.63, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): COc1ccc(-c2cncc(NS(=O)(=O)c3cc(Cl)ccc3OC)c2)cc1
InChIKey: GSJUYLFAODJCMV-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 404.88, ALogP 4.22, HBA 5, HBD 1, PSA 77.52, QED 0.67