lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC(=O)[C@H](Cc1c[nH]c2ccccc12)n1cc(COc2nc(Cl)nc(N3CCCCC3)n2)nn1
InChIKey: HNEPTWGLGJYBQA-IBGZPJMESA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.96, ALogP 3.12, HBA 10, HBD 1, PSA 123.94, QED 0.37
Compound (SMILES): COc1cccc(CN2CCc3cc(-c4ccc5[nH]ncc5c4)ccc3C2=O)c1
InChIKey: XTPHWCDWCWGAAN-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 40 mins in presence of [gamma-33P]ATP by radiometric scintillation assay
Measurement: IC50 = 632 nM (pChEMBL 6.199999809265137)
Descriptors: MW 383.45, ALogP 4.44, HBA 3, HBD 1, PSA 58.22, QED 0.57
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3cccc(C)c3C)CC2)c(=O)c2c(F)cccc12
InChIKey: IGSJDSBITWLUTD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 327 nM (pChEMBL 6.489999771118164)
Descriptors: MW 523.61, ALogP 2.54, HBA 8, HBD 1, PSA 96.77, QED 0.43
Compound (SMILES): Nc1nc2[nH]c(CCCSc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1
InChIKey: AVVUJZMZPKPMOO-HNNXBMFYSA-N
Target: Trifunctional purine biosynthetic protein adenosine-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22102
Assay: Inhibition of GARFTase in human KB cells expressing RFC/FRalpha/PCFT assessed as reduction in cell growth after 96 hrs in presence of folic acid by Cell-Titer Blue assay
Measurement: IC50 = 757 nM (pChEMBL 6.119999885559082)
Descriptors: MW 473.51, ALogP 1.61, HBA 7, HBD 6, PSA 191.26, QED 0.18
Compound (SMILES): CC(=O)N1CCC(c2nsc(Nc3ncc(Sc4ccccn4)cc3Oc3cccc4ncccc34)n2)CC1
InChIKey: JNDNJMYZHYPZGD-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of glucokinase (unknown origin) in presence of 4% human serum albumin
Measurement: EC50 = 504 nM (pChEMBL 6.300000190734863)
Descriptors: MW 555.69, ALogP 6.29, HBA 10, HBD 1, PSA 106.02, QED 0.25
Compound (SMILES): O=C(CC1c2ccccc2N=C(SCCCCCN2CCCC2)N1c1ccc(-c2ccccc2)cc1)NCc1ccccc1
InChIKey: NGUAIHUUBCVZQW-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human Cav3.2 expressed in tsA-201 cells by patch clamp electrophysiology
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 602.85, ALogP 8.61, HBA 5, HBD 1, PSA 47.94, QED 0.17
Compound (SMILES): CCN1C(=O)c2ccccc2N(C)c2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)ncc21
InChIKey: DDJBEYRDSUCNLT-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate measured after 1 hr by Alexa fluor-647 ADP tracer-based ADAPTA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 515.62, ALogP 3.8, HBA 8, HBD 2, PSA 102.93, QED 0.51
Compound (SMILES): CCCN1CCc2cccc3c2C1Cc1ccc(NS(C)(=O)=O)cc1-3
InChIKey: AMDADTMHUSETIS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7A receptor expresssed in stable HEK cell membrane incubated for 90 mins by microbeta counting method
Measurement: Ki = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 356.49, ALogP 3.59, HBA 3, HBD 1, PSA 49.41, QED 0.91
Compound (SMILES): CN1[C@@H]2CC[C@H]1C[C@H](OC(=O)Nc1ccc(F)cc1-c1ccccc1)C2
InChIKey: VMRVZDOCRVNUDB-BCDXTJNWSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 354.43, ALogP 4.67, HBA 3, HBD 1, PSA 41.57, QED 0.87
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3ccccc3Cl)CC2)c(=O)c2ccccc12
InChIKey: YTCWCXBDZAGXAX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 6180 nM (pChEMBL 5.210000038146973)
Descriptors: MW 512.01, ALogP 2.44, HBA 8, HBD 1, PSA 96.77, QED 0.44
Compound (SMILES): O=C(N[C@@H]1CCCc2c1cnn2-c1ccccc1F)c1cc(Br)ccn1
InChIKey: CPQPLJPWRQGPBK-OAHLLOKOSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of recombinant human DHODH using dihydroorotic acid as substrate measured for 68 mins by DCIP based colorimetric assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 415.27, ALogP 3.98, HBA 4, HBD 1, PSA 59.81, QED 0.7
Compound (SMILES): CCNS(=O)(=O)c1ccccc1Nc1ncnc(Nc2ccc(N3CCN(C)CC3)c(OCC(=O)O)c2)n1
InChIKey: HDDJGLQYFZACAI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of N-terminal GST-tagged human VEGFR2 cytoplasmic domain (790-1356 end amino acid residue) expressed in baculovirus expression system preincubated for 30 to 120 mins followed by incubation with substrate and ATP for 30 mins by off-chip mobility shift assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 542.62, ALogP 1.87, HBA 11, HBD 4, PSA 161.91, QED 0.28
Compound (SMILES): O=C1C=C(c2cccnc2)C(=O)c2c(CCNS(=O)(=O)c3ccccc3)c[nH]c21
InChIKey: IQMCEENRPYLSKQ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IFNgamma-stimulated IDO1 in human HeLa cells
Measurement: EC50 = 4920 nM (pChEMBL 5.309999942779541)
Descriptors: MW 407.45, ALogP 2.39, HBA 5, HBD 2, PSA 108.99, QED 0.65
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cc2c1O[C@H](C)[C@H]2c1ccccc1
InChIKey: OZYUZRYSLNMCRL-XIKOKIGWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 350.42, ALogP 2.85, HBA 3, HBD 2, PSA 67.43, QED 0.89
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc([N+](=O)[O-])c3)CC2)cc1
InChIKey: KHRJNSMYBNDMTF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 28.6 nM (pChEMBL 7.539999961853027)
Descriptors: MW 418.43, ALogP 0.84, HBA 6, HBD 1, PSA 143.92, QED 0.58
Compound (SMILES): COc1ccc(C(=O)CSc2nccc(Nc3ccc(S(=O)(=O)Nc4ccccn4)cc3)n2)cc1
InChIKey: LRWGLPDQVPGIPV-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 507.6, ALogP 4.4, HBA 9, HBD 2, PSA 123.17, QED 0.18
Compound (SMILES): O=C(CCc1ccc(Cl)cc1)C(=O)NCCc1ccccc1
InChIKey: QGGUZCHPVXJPCP-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 315.8, ALogP 3.2, HBA 2, HBD 1, PSA 46.17, QED 0.8
Compound (SMILES): COc1ccc(C(=O)CSc2nccc(Nc3ccc(S(N)(=O)=O)cc3)n2)cc1
InChIKey: HAIDQSKDSFANTR-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 430.51, ALogP 2.85, HBA 8, HBD 2, PSA 124.27, QED 0.32
Compound (SMILES): N#CN1CC[C@H](OCc2ccc(-c3ccccc3)cc2)C1
InChIKey: KIUBKYHEXRZYKC-SFHVURJKSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 278.36, ALogP 3.43, HBA 3, HBD 0, PSA 36.26, QED 0.8
Compound (SMILES): CNC(=O)c1cc(C(=O)NC)c(=O)n(Cc2ccccc2)c1
InChIKey: DANLNXYNIAMHCE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 299.33, ALogP 0.62, HBA 4, HBD 2, PSA 80.2, QED 0.87
Compound (SMILES): CC(C)N(C(=O)c1cccc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: CLEDVPXGVTYVTP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 366.34, ALogP 3.88, HBA 3, HBD 2, PSA 69.64, QED 0.64
Compound (SMILES): N#Cc1cnc(-c2cnc3[nH]ccc3c2)nc1N1C[C@@H]2C[C@H]1CN2c1cccc(F)c1
InChIKey: WHKNAESTUDYHFE-PMACEKPBSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: This assay was developed and further optimized from a kit produced by Upstate (Millipore catalog #33-047) (Millipore Sigma, Billerica Mass., USA) and has been configured for high throughput screening (HTS) and structure-activity relationship (SAR) screening. Briefly, this procedure exploits the exquisite specificity and high affinity binding of enzyme reaction substrate phosphatidyl(3,4,5)triphosphate (PIP3) to the GRP1 pleckstrin homology (PH) domain to generate the signal. In the absence of PIP3, an HTRF (Homogeneous Time-Resolved Fluorescence energy transfer) complex is formed consisting of europium (u)-labeled anti-GST, GST tagged GRP1-PH domain, biotin-PIP3 (biotinylated-PIP3) and streptavidin conjugated APC (Allophycocyanin). The native PIP3 produced by PI3-Kinase activity disrupts in a competitive manner the biotin-PIP3 from the pleckstrin homology (PH) domain, resulting in the loss of energy transfer (HTRF complex) and a decrease in the signal. The format of this assay is the same for all 4 isoforms of PI3K; the differences lie in the concentration of enzyme used to achieve robust assay window. The alpha, beta, and delta assays are run at 0.5, 1, and 0.3 nM enzymes and the gamma assay is run at 5 nM enzyme. The ATP concentration is 100 uM in the alpha, beta, and delta assays and 50 uM adenosine triphosphate (ATP) in the gamma assay. All reactions are run at 5 uM PIP2.
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 411.44, ALogP 3.5, HBA 6, HBD 1, PSA 84.73, QED 0.56
Compound (SMILES): COc1ccc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccc(Cl)cc2)cc1OC
InChIKey: QXGBJJBYBGQCBO-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 471.99, ALogP 4.11, HBA 5, HBD 2, PSA 79.9, QED 0.63
Compound (SMILES): CCN(C(=O)N1CCC(C(=O)c2ccc3ncn(C)c3c2)CC1)c1ccc(C(=O)O)cc1
InChIKey: RGDWKTYYFMMDGT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human GST-tagged tankyrase 2 autophosphorylation
Measurement: IC50 = 0.27 nM (pChEMBL 9.569999694824219)
Descriptors: MW 434.5, ALogP 3.81, HBA 5, HBD 1, PSA 95.74, QED 0.62
Compound (SMILES): c1cn2cc(-c3cnc4cc[nH]c4n3)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: YOPSHVHBLGMPGU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 467.54, ALogP 2.93, HBA 9, HBD 2, PSA 99.5, QED 0.41
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N(CC)CC)c(C(F)F)c1F)C(F)(F)F
InChIKey: JNEUDLAVCJEDDA-AWEZNQCLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 632.65, ALogP 4.49, HBA 7, HBD 3, PSA 128.7, QED 0.3
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CC[C@@H](F)C[C@@H]2C)c(Cl)c1Cl)C(F)(F)F
InChIKey: USDMFVQYIFPILC-RWMBFGLXSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 663.54, ALogP 4.81, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc(Br)c3)CC2)cc1
InChIKey: ODJZGQFXLXQHJA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 452.33, ALogP 1.69, HBA 4, HBD 1, PSA 100.78, QED 0.77
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc5c(c4)OCO5)c(C)c3c2)CC1
InChIKey: KHPAKZBEZQECBS-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 391.52, ALogP 4.27, HBA 4, HBD 2, PSA 49.52, QED 0.68
Compound (SMILES): O=C(O)c1ccccc1Nc1cccc(Cl)c1-c1ccc2nonc2c1
InChIKey: SSJWKWGQPFJSSE-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Displacement of 1,8-ANS from recombinant human 6His-tagged FABP3 expressed in Escherichia coli BL21 DE3 incubated for 15 mins followed by 1,8-ANS addition and measured after 3 mins by fluorescence based assay
Measurement: Ki = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 365.78, ALogP 4.99, HBA 5, HBD 2, PSA 88.25, QED 0.53
Compound (SMILES): Cc1noc(C)c1-c1cc2ncc3c(c2cc1OCCCN(C)C)n([C@H](C)c1ccccn1)c(=O)n3C
InChIKey: MBTGLUILOPYDGX-GOSISDBHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged human BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant expressed in Escherichia coli after 1 hr by TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 500.6, ALogP 4.49, HBA 9, HBD 0, PSA 91.21, QED 0.29
Compound (SMILES): CN(C)C1CCc2c(cccc2-c2cncc3ccccc23)C1
InChIKey: FXINCGSMEJQTMY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT7A receptor expressed in HEK293 cell membranes incubated for 90 mins by scintillation counting method
Measurement: Ki = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 302.42, ALogP 4.32, HBA 2, HBD 0, PSA 16.13, QED 0.7
Compound (SMILES): C[C@@H]1C[C@H]1CNC(=O)[C@@H]1C[C@H]1[C@]12CN(c3ncccn3)C[C@H]1CSC(N)=N2
InChIKey: UKXLLHCQBVONES-MPDRSUQMSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 (1 to 460 residues) expressed in HEK293 cells using mcaFRET peptide as substrate after 20 hrs by FRET assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 386.52, ALogP 1.12, HBA 7, HBD 2, PSA 96.5, QED 0.79
Compound (SMILES): COC(=O)C1CCCN(Cc2ccc3nc4n(c(=O)c3c2)-c2ccc(F)cc2C4=O)C1
InChIKey: KIGHWMYCRYPNLO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 421.43, ALogP 2.45, HBA 7, HBD 0, PSA 81.5, QED 0.47
Compound (SMILES): O=C(On1nnc2ccccc21)c1c[nH]c2ccccc12
InChIKey: ZUICDDCLDBHMCH-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of SIRT2 deacetylation activity (unknown origin) using H4K8Ac (3 to 13 residues) as substrate by HPLC analysis
Measurement: IC50 = 22100 nM (pChEMBL 4.659999847412109)
Descriptors: MW 278.27, ALogP 2.18, HBA 5, HBD 1, PSA 72.8, QED 0.57
Compound (SMILES): CCN(CC)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: OZWVOBLSVPGTGH-NSHDSACASA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 619.51, ALogP 4.33, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): CCCCc1c(Nc2cccc3c2CCN(C)C3)cnn(C)c1=O
InChIKey: SIDLAJMJLFGVGU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to human partial length BRD9 (R130 to V259 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 326.44, ALogP 2.85, HBA 5, HBD 1, PSA 50.16, QED 0.92
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)cs1)c1ccc(C(=O)c2ccccc2)cc1
InChIKey: ARPJLXJZGILMIN-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 384.46, ALogP 5.29, HBA 4, HBD 1, PSA 59.06, QED 0.48
Compound (SMILES): CC(C)n1c(=O)sn(CCc2ccccc2)c1=O
InChIKey: YWDUHMQLSBNQFA-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) assessed as reduction in IsdA (64 to 323 residues) transpeptidation incubated for 20 mins by SDS-PAGE analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 264.35, ALogP 1.9, HBA 5, HBD 0, PSA 44, QED 0.85
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCC4CCOCC4)s3)C2)cc1
InChIKey: XPTUNGFRXJHQJG-HXUWFJFHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.66, ALogP 4.5, HBA 7, HBD 2, PSA 83.56, QED 0.42
Compound (SMILES): C/C=C/C[C@@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C)NC(=O)[C@H](Cc2ccc(O)c([N+](=O)[O-])c2)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](Cc2cn(C(C)(C)[C@H](O)CCl)c3ccccc23)NC1=O
InChIKey: DFIBTJXEVPMOBW-CFTAYRILSA-N
Target: ATP-dependent Clp protease ATP-binding subunit ClpC1 (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WPC9
Assay: Binding affinity to recombinant full length Mycobacterium tuberculosis H37Rv ClpC1 (1 to 842 residues) expressed in Escherichia coli BL21 cells by surface plasmon resonance analysis
Measurement: Kd = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 1064.72
Compound (SMILES): CC(C)=CC[C@]12Oc3cc(O)c([C@H]4C=C(C)C[C@H](c5ccc(O)cc5O)C4C(=O)c4ccc(O)cc4O)c(O)c3C(=O)[C@@]1(O)Oc1cc(O)ccc12
InChIKey: XETHJOZXBVWLLM-OEMJFCHDSA-N
Target: Beta-glucuronidase (SINGLE PROTEIN), Homo sapiens
UniProt: P08236
Assay: Inhibition of whole human gut bacterial beta-glucuronidase
Measurement: IC50 = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 708.72, ALogP 6.25, HBA 12, HBD 8, PSA 214.44, QED 0.08
Compound (SMILES): N#CCC(=O)N1CC=C(c2cccc3nc(NC(=O)C4CC4)nn23)CC1
InChIKey: IOEFLIHBEXZAFY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) in presence of ATP at Km concentration by caliper assay
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 350.38, ALogP 1.61, HBA 6, HBD 1, PSA 103.39, QED 0.9
Compound (SMILES): O=C(Nc1ncc(-c2ccccc2)s1)c1ccc(C(=O)c2ccccc2)cc1
InChIKey: FLTDSTBWKYBFSI-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 384.46, ALogP 5.29, HBA 4, HBD 1, PSA 59.06, QED 0.48
Compound (SMILES): c1cn2cc(-c3ccc4cn[nH]c4c3)nc(Nc3ccc(N4CC5(CCOCC5)C4)cc3)c2n1
InChIKey: QWDPLTNITSUDPA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 451.53, ALogP 4.63, HBA 7, HBD 2, PSA 83.37, QED 0.41
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)C#N)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: YIJASKHSLJFFRO-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 658.53, ALogP 5.2, HBA 7, HBD 2, PSA 132.26, QED 0.38
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Oc2ccccc2)cc1
InChIKey: YWYSSOKJGYXYIM-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 387.48, ALogP 4.73, HBA 3, HBD 1, PSA 55.4, QED 0.51
Compound (SMILES): CNC(=O)c1cc(C(=O)NCCOC)cc2c1O[C@H](C)[C@H]2c1ccccc1
InChIKey: GZJPFVGFRGYSAO-ACJLOTCBSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 368.43, ALogP 2.34, HBA 4, HBD 2, PSA 76.66, QED 0.77
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCC2CCCCC2)CC(=O)NC2CCC2)nn1-c1ccc(F)cc1
InChIKey: QVGYRVJMENXXAI-VWLOTQADSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 576.71, ALogP 6.21, HBA 6, HBD 2, PSA 94.48, QED 0.27
Compound (SMILES): CCN(c1ccc(C(=O)NO)cc1)S(=O)(=O)c1cccc(C(F)(F)F)c1
InChIKey: QDLQWVBUGGQYHL-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 = 712 nM (pChEMBL 6.150000095367432)
Descriptors: MW 388.37, ALogP 3.04, HBA 4, HBD 2, PSA 86.71, QED 0.61
Compound (SMILES): COc1cc(C(=O)NOCCCCCC(=O)NO)cc(OC)c1OC
InChIKey: WSFZAZKSARVIJQ-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4
Measurement: Ki = 93100 nM (pChEMBL 4.03000020980835)
Descriptors: MW 356.38, ALogP 1.44, HBA 7, HBD 3, PSA 115.35, QED 0.31
Compound (SMILES): O=C([C@H]1Cc2cc(Cl)cc(-c3ccnc4cc(CO)sc34)c2O1)N1CCNCC1
InChIKey: YCGQVRKPSRARFT-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94782
Assay: Inhibition of His6-tagged human USP1 expressed in insect Sf21 cells coexpressing untagged UAF1 assessed as cleavage of Ubiquitin-Rhodamine110-glycine to Ubiquitin and Rhodamine110-glycine using Ubiquitin-Rhodamine110-glycine as substrate by fluorescence based analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 429.93, ALogP 2.84, HBA 6, HBD 2, PSA 74.69, QED 0.67
Compound (SMILES): C[C@]1(C(=O)O)CC[C@H](CC(=O)N2CCc3c(n(Cc4ccc(F)cc4F)c4ncccc34)C2)CC1
InChIKey: ITUYIHBIYFMSGB-KJGDFQNHSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of LysoPLD activity of ATX in human plasma assessed as reduction in choline release using LPC(16:0) as substrate incubated for 15 hrs
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 481.54, ALogP 4.92, HBA 4, HBD 1, PSA 75.43, QED 0.56
Compound (SMILES): Cc1ccc(CN2CCCN(C(=O)c3cc4ccccc4o3)CC2)c(C)c1
InChIKey: NPKJCPIQHPJRBY-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-Di-o-tolylguanidine from sigma-2 receptor in rat liver membranes after 120 mins by scintillation counting method
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 362.47, ALogP 4.4, HBA 3, HBD 0, PSA 36.69, QED 0.69
Compound (SMILES): C=CC(=O)N1CC(Oc2cccc3[nH]c(-c4n[nH]c5cc(C(F)F)ccc45)cc23)C1
InChIKey: ONAWENGDNSLLBY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 408.41, ALogP 4.42, HBA 3, HBD 2, PSA 74.01, QED 0.48
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3ccc(C(=N)N)cc3Cl)c2O)cc1
InChIKey: SNGWZJUYWHIFIM-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor X (unknown origin) using CH3O-CO-D-CHG-Gly-Arg-pNA-AcOH as substrate by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 353.81, ALogP 3.84, HBA 5, HBD 4, PSA 107.91, QED 0.42
Compound (SMILES): Cc1c(-c2cc(-c3nnc[nH]3)c3nc(C)n(-c4ccnc5c(F)ccc(F)c45)c3c2)ccnc1N
InChIKey: FQHVIORVLAQSKW-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 468.47, ALogP 4.9, HBA 7, HBD 2, PSA 111.19, QED 0.38
Compound (SMILES): Cn1cc(-c2ccc3c(c2)CCN3C(=O)[C@H](NCCc2ccc(C#N)cc2)c2ccccc2)cn1
InChIKey: PLIOUZZJBKYIKV-MUUNZHRXSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Biochemical Assay: The full length p300 SPA assay was run following the same protocol as p300 HAT SPA assay, but used 6 nM purified full length p300 (purchased from Active Motif) in place of the purified p300-HAT domain.Select compounds were also evaluated in a H3K18Ac MSD cellular assay that measures the ability of compounds to inhibit the the acetylation of chromatin at H3K18, a process catalyzed by p300 and CBP. In a typical experiment the p300 HAT inhibitory activity inside cells of the compounds described herein was determined in accordance with the following experimental method. 20 k HCT-116 cells per well are plated in 75 μL RPMI+10% FBS media the night before treatment. Compounds plated in DMSO at 4× final concentration are resuspended in 30 μL RPMI+10% FBS, then 25 μL is combined with corresponding wells containing cells. Treated cells are incubated for 2 hr at 37° C., then lysed in 500 μL final volume and frozen at −80° C. MSD plates (Meso Scale Discovery) are coated overnight at 4° C. with 60 μL 1:500 α-total histone antibody (Millipore MAB3422) in PBS. Plates are then blocked with 5% BSA in TBST shaking at RT for 1 hr, washed, and 30 μL lysate added to each well for 2 hr shaking at RT. Plates are washed and 25 μL 1:216 α-H3K18ac antibody (CST 9675) in PBS added, then incubated for 1 hr shaking at RT. Plates are washed again, then 25 μL 1:1000 Sulfo-Tag goat α-rabbit antibody (Meso Scale Discovery R32Ab-1) in PBS is added for 1 hr shaking at RT. Plates are washed once more, then 150 μL 1× Read Buffer (MSD #R92TD-3) is added to all wells and read on MSD SECTOR Imager 2400 using the conventional read setup.
Measurement: IC50 = 31.8 nM (pChEMBL 7.5)
Descriptors: MW 461.57, ALogP 4.42, HBA 5, HBD 1, PSA 73.95, QED 0.44
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)N3CC4(C3)CS(=O)(=O)C4)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: IMEJKVUKSAQCKI-INIZCTEOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 721.6, ALogP 4.18, HBA 8, HBD 1, PSA 133.82, QED 0.42
Compound (SMILES): Cc1c(N2CCCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: YQOLEILXOBUDMU-KRWDZBQOSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate incubated for 15 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 544.88, ALogP 5.94, HBA 4, HBD 2, PSA 82.53, QED 0.37
Compound (SMILES): Cc1nn(-c2ccccn2)c2ncc(C(=O)c3ccccc3O)cc12
InChIKey: LFBMVPHWBALPPW-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of sepiapterin reductase (unknown origin)
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 330.35, ALogP 3.06, HBA 6, HBD 1, PSA 80.9, QED 0.58
Compound (SMILES): Fc1ccc(C(SCCCN2CCN(CCCc3ccccc3)CC2)c2ccc(F)cc2)cc1
InChIKey: ODAMMHVGHBSSJU-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 480.67, ALogP 6.43, HBA 3, HBD 0, PSA 6.48, QED 0.29
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GKYDUZGIMDOXEK-CVUOCSEZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 1800 nM (pChEMBL 5.75)
Descriptors: MW 951.1, ALogP -3.41, HBA 12, HBD 17, PSA 435.06, QED 0.02
Compound (SMILES): N#Cc1cnc(N2Cc3cn[nH]c3C2)nc1N1C[C@@H]2C[C@H]1CN2c1cccc(F)c1
InChIKey: SKNVDLZUZJXRRZ-ROUUACIJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K delta in human whole blood assessed as inhibition of anti-IgE-stimulated CysLt release in basophils preincubated for 30 mins followed by anti-IgE stimulation and measured after 20 mins
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 402.44, ALogP 2.2, HBA 7, HBD 1, PSA 87.97, QED 0.72
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1ccc(Cl)c(Cl)c1)O[C@H]1CN2CCC1CC2
InChIKey: LVPIEYVPDBYBIT-IBGZPJMESA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 409.29, ALogP 5.44, HBA 3, HBD 1, PSA 41.57, QED 0.73
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2ccnc(SCC(=O)c3ccc(Cl)cc3)n2)cc1
InChIKey: HERBPJQZNGCUMI-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 434.93, ALogP 3.5, HBA 7, HBD 2, PSA 115.04, QED 0.33
Compound (SMILES): CC(C)Nc1cc(Nc2ccc3ncsc3c2)ncc1C(=O)NC[C@@H](F)C(C)(C)O
InChIKey: PXWXZTKRZLFCJV-GOSISDBHSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human PBMC assessed as inhibition of LTA-induced IL-6 production preincubated for 30 mins followed by LTA-stimulation and measured after 5 hrs by ELISA
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 431.54, ALogP 4.09, HBA 7, HBD 4, PSA 99.17, QED 0.43
Compound (SMILES): Cc1c(N2CC[C@@H]([C@H](C)N)C2)c(F)cc2cc(C(=O)O)c(=O)n(C3CC3)c12
InChIKey: WDEFFRJHKJGSLD-NWDGAFQWSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks patch clamp electrophysiology method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 373.43, ALogP 2.66, HBA 5, HBD 2, PSA 88.56, QED 0.86
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cc5OC)c(=O)c4c3)cc12
InChIKey: BASMYKLUFZUQTO-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 1b by Taqman probe based RT-PCR analysis
Measurement: EC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 672.71, ALogP 5.88, HBA 8, HBD 1, PSA 123.74, QED 0.21
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3ccc(C)c(C)c3)CC2)c(=O)c2cc(F)ccc12
InChIKey: LWVZTCUPQKWJND-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]imipramine from SERT receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 278 nM (pChEMBL 6.559999942779541)
Descriptors: MW 523.61, ALogP 2.54, HBA 8, HBD 1, PSA 96.77, QED 0.43
Compound (SMILES): C=CCN1CCc2cc(OC)c(O)cc2C(c2ccccc2Cl)C1
InChIKey: GSYJGVACPBIRCA-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 264.4 nM (pChEMBL 6.579999923706055)
Descriptors: MW 343.85, ALogP 4.23, HBA 3, HBD 1, PSA 32.7, QED 0.84
Compound (SMILES): Nc1nc(NCc2ccc(S(N)(=O)=O)cc2)nc2sc(-c3ccco3)nc12
InChIKey: GGBHOXXNFSSUEW-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241383 from human A2AR expressed in CHO cells by competitive binding assay
Measurement: Ki = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 402.46, ALogP 2.19, HBA 9, HBD 3, PSA 150.02, QED 0.46
Compound (SMILES): N#C[C@]1(C2CC2)C(=O)N2C[C@H]1COC/C=C\COCc1cccc(n1)Nc1cc2ccn1
InChIKey: HTEKLZHVQBWTOT-WDPAYFAUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 431.5, ALogP 3.21, HBA 7, HBD 1, PSA 100.37, QED 0.69
Compound (SMILES): Cc1cc(-c2cnc3c(NCCC(F)(F)F)nccn23)ccc1C(=O)NC1CC1
InChIKey: MSHWBGIAMYRZSO-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 667 nM (pChEMBL 6.179999828338623)
Descriptors: MW 403.41, ALogP 3.96, HBA 5, HBD 2, PSA 71.32, QED 0.65
Compound (SMILES): CCC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: CZPFBLHFGKUTTQ-TXVKUACNSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 492.6, ALogP 6.49, HBA 5, HBD 0, PSA 79.53, QED 0.41
Compound (SMILES): COc1ccc(CCNC(=O)C(=O)CCCc2ccccc2)cc1OC
InChIKey: NNBYHRRMRFFJJK-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 355.43, ALogP 2.95, HBA 4, HBD 1, PSA 64.63, QED 0.67
Compound (SMILES): NS(=O)(=O)c1ccc(Oc2ccc(F)c(Cl)c2)c(CN2CCN(C3COC3)CC2)c1
InChIKey: UFMSOOQAFBHAJW-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Agonist activity at His6-tagged-human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli BL21-CodonPlus-RIPL cells assessed as increase in SOS1-mediated GDP/GTP nucleotide exchange upon K-Ras G12D mutant (1 to 169 residues) by BODIPY-GDP assay
Measurement: EC50 = 7880 nM (pChEMBL 5.099999904632568)
Descriptors: MW 455.94, ALogP 2.44, HBA 6, HBD 1, PSA 85.1, QED 0.72
Compound (SMILES): COCc1cncc(-c2ccc3[nH]nc(C(=O)NCC4CCOCC4)c3c2)c1
InChIKey: JWQMLWIDIFDPFG-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in tail current by measuring tail current amplitude measured after deploarization to +20 mV for 2s followed by 1s pulse to -40 mV by whole cell patch clamp assay
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 380.45, ALogP 2.93, HBA 5, HBD 2, PSA 89.13, QED 0.69
Compound (SMILES): O=C(Nc1ccc(-c2nc3ccccc3[nH]2)cc1)c1ccc(Br)cc1
InChIKey: DYLDUUQPDPOLLA-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 55000 nM (pChEMBL 4.260000228881836)
Descriptors: MW 392.26, ALogP 5.24, HBA 2, HBD 2, PSA 57.78, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3ccccc3F)CC2)cc1
InChIKey: NXIFLMUSIPVLEA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 28.4 nM (pChEMBL 7.550000190734863)
Descriptors: MW 391.42, ALogP 1.07, HBA 4, HBD 1, PSA 100.78, QED 0.85
Compound (SMILES): Cc1cccc(N2CCN(CCCC(=O)NCn3nc(CC(N)=O)c4cccc(F)c4c3=O)CC2)c1C
InChIKey: CHTMCSSVDNUSJB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 2014 nM (pChEMBL 5.699999809265137)
Descriptors: MW 508.6, ALogP 1.86, HBA 7, HBD 2, PSA 113.56, QED 0.46
Compound (SMILES): COc1ccccc1SC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: HLUJXEXDDSDFKA-QATBIIFWSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: [35S] GTPgammaS Binding Assays: Compounds were loaded in a 384 Falcon v-bottom plate (0.5 ul/well in a 11 point, 3-fold dilution). Membranes prepared from S1P1/CHO cells or EDG3-Gal5-bla HEK293T cells (EDG3 equivalent S1P3) were added to the compound plate (40 ul/well, final protein 3 ug/well) with MULTIDROP. [35S] GTP (1250 Ci/mmol, Perkin Elmer) was diluted in assay buffer: 20 mM HEPES, pH7.5, 10 mM MgCl2, 150 mM NaCl, 1 mM EGTA (ethylene glycol tetraacetic acid), 1 mM DTT (Dithiothreitol), 10 uM GDP, 0.1% fatty acid free BSA, and 10 ug/ml Saponin to 0.4 nM. 40 ul of the [35S] GTP solution was added to the compound plate with a final concentration of 0.2 nM. The reaction was kept at room temperature for 45 min. At the end of incubation, all the mixtures in the compound plate were transferred to Millipore 384-well FB filter plates via the VELOCITY11 Vprep liquid handler. The filter plate was washed with water 4 times by using the manifold Embla plate washer and dried at 60° C. for 45 min. MicroScint 20 scintillation fluid (30 ul) was added to each well for counting on the Packard TOPCOUNT. EC50 is defined as the agonist concentration that corresponds to 50% of the Ymax (maximal response) obtained for each individual compound tested.
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 477.56, ALogP 4.67, HBA 5, HBD 3, PSA 102.01, QED 0.38
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)CC2(CCCCC2)CNC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC1=O.O=C(O)C(F)(F)F
InChIKey: MSIIVKDPQBOVIB-JDCPXUKWSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of vitronectin binding to recombinant human integrin alphaV (Phe31 to Val992 residues) beta5 (Gly24 to Asn719 residues) expressed in CHO cells by ELISA based solid phase binding assay
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 628.73, ALogP -0.99, HBA 7, HBD 9, PSA 244.7, QED 0.1
Compound (SMILES): Cl.c1cncc(OC[C@@H]2C[C@H]3C[C@H]3N2)c1
InChIKey: ZBPJOTASPXCCCA-WUKJGCQFSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in IMR32 cell membrane by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 190.25, ALogP 1.21, HBA 3, HBD 1, PSA 34.15, QED 0.78
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CCC(F)(F)F)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: BPEYOXRKPSHIFR-VPUSJEBWSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 613.73, ALogP 6.77, HBA 6, HBD 2, PSA 100.21, QED 0.19
Compound (SMILES): Cc1ccnc(C(=O)N[C@@H]2CCCc3c2cnn3-c2cc(C)ccc2F)c1
InChIKey: JGJXMQVCWASLHC-QGZVFWFLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition Assay: Assay B: Example compounds as described herein were dispensed with an acoustic liquid handler, Echo 550 (Labcyte) to a maximum volume of 50 nl per well in a 384 well plate. DHODH enzyme assays were performed with 4 nM recombinant human DHODH (purified essentially as described by Walse et. al., Biochemistry, 47, 8929-8936 (2008)). The reaction mixture consisted of 2 mM DL-dihydroorotic acid (#D7003, Sigma-Aldrich), 100 μM 3,4-dimethoxy-5-methyl-p-benzoquinone (#D9150, Sigma-Aldrich), and 200 μM 2,6-dichlorophenolindophenol sodium salt (DCIP) (#D1878, Sigma-Aldrich) in enzyme buffer (50 mM Tris-HCl pH 8.0, 0.1% Triton X-100, 150 mM KCl) in a final volume of 50 μl per well. A stock solution of 80 mM DCIP was prepared in DMSO just before use. Loss in absorbance by chromogen DCIP was measured at 595 nm at RT every 2 min for an hour with a plate reader (Envision, Perkin Elmer).
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 364.42, ALogP 3.83, HBA 4, HBD 1, PSA 59.81, QED 0.77
Compound (SMILES): O[C@H](Cc1ccccc1)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: KQCSWOPIWOIUQE-HHHXNRCGSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 813 nM (pChEMBL 6.090000152587891)
Descriptors: MW 482.64, ALogP 5.01, HBA 4, HBD 1, PSA 26.71, QED 0.44