lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)c(F)c1)c1cc(C#N)ccc1F
InChIKey: MULKIBHRPCRKGZ-JTQLQIEISA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 10727 nM (pChEMBL 4.96999979019165)
Descriptors: MW 438.46, ALogP 4.41, HBA 6, HBD 2, PSA 94.88, QED 0.59
Compound (SMILES): C[C@@H]1CC(c2cnc3c(C#N)nn([C@H](C)c4ccc(Cl)cc4Cl)c3n2)=CC[C@@H]1N1CCC[C@H]1CO
InChIKey: KQZLRWGGWXJPOS-NLFPWZOASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.46, ALogP 5.25, HBA 7, HBD 1, PSA 90.86, QED 0.5
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@@H]1CCN(S(C)(=O)=O)c2ccc(Cc3cc4ccccc4o3)cc21.O=C(O)C(F)(F)F
InChIKey: FBHHVOGHYMRVBB-MFHXMFJOSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 1 hr
Measurement: EC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 547.68, ALogP 4.24, HBA 6, HBD 3, PSA 125.87, QED 0.32
Compound (SMILES): CCOC1Cc2ccccc2[C@]2(CC[C@H](N(C)CC3CCCCC3)CC2)O1
InChIKey: IKMGBUAQTLFZNA-IQEXNZJNSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in human RT4 cell membranes incubated for 120 mins in the presence of sigma1 receptor ligand (+)-pentazocine by scintillation counting method
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 371.57, ALogP 5.27, HBA 3, HBD 0, PSA 21.7, QED 0.7
Compound (SMILES): O=C(O)CN1C(=O)/C(=C/c2cccc(OCCc3ccccc3)c2)SC1=S
InChIKey: STKZJPQZNBVHCZ-ATVHPVEESA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Non-competitive inhibition of human full-length GST-fused PTP1B expressed in bacterial expression system assessed as dissociation constant of enzyme-inhibitor-substrate complex using pNPP as substrate by Michaelis-Menten plot analysis
Measurement: Ki = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 399.49, ALogP 3.59, HBA 5, HBD 1, PSA 66.84, QED 0.57
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)C2CCCCC2)cc1Cl
InChIKey: XESFZDLAWXFOQS-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 424.93, ALogP 0.82, HBA 6, HBD 3, PSA 143.63, QED 0.62
Compound (SMILES): CS(=O)(=O)Nc1ccc2oc(-c3ccccc3)nc2c1
InChIKey: MEFGMEZNBFFZJC-UHFFFAOYSA-N
Target: Malate dehydrogenase, mitochondrial (SINGLE PROTEIN), Sus scrofa
UniProt: P00346
Assay: Inhibition of refolded pig heart mitochondrial MDH preincubated with Escherichia coli GroEL/GroES for 45 mins using sodium mesoxalate as substrate followed by compound addition and measured after 20 to 30 mins by spectrometric analysis
Measurement: IC50 > 63000 nM (pChEMBL 4.201000213623047)
Descriptors: MW 288.33, ALogP 2.87, HBA 4, HBD 1, PSA 72.2, QED 0.8
Compound (SMILES): C=CCCn1cc(-c2cncc(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: QAORWPLEPWLSPU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Inhibition of recombinant His-tagged BRD9 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 378.43, ALogP 2.44, HBA 5, HBD 1, PSA 80.22, QED 0.69
Compound (SMILES): CCc1cc(Cl)c(OC)c(N2CCN(CCCCNC(=O)c3cc4ccccc4o3)CC2)c1
InChIKey: NIENYVQCIJZKMD-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor expressed in CHO cells assessed as inhibition of quinpirole-stimulated mitogenesis incubated for 16 hrs in presence of [3H]thymidine by scintillation spectrometric analysis
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 470.01, ALogP 4.99, HBA 5, HBD 1, PSA 57.95, QED 0.45
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4C[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3F)c(=O)[nH]1
InChIKey: FSQBZPVQQBPKOW-FFNOWKGOSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 660.41, ALogP -0.34, HBA 18, HBD 5, PSA 289.19, QED 0.17
Compound (SMILES): Cn1cc(-c2cn3nccc3c(-c3cnn([C@]4(CC#N)C[C@@H](C#N)C4)c3)n2)cn1
InChIKey: XPLZTJWZDBFWDE-OYOVHJISSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK2/TYK2 signaling pathway in human whole blood lymphocytes assessed as reduction in IL-23 induced STAT3 phosphorylation preincubated for 45 mins followed by IL-23 addition and measured measured after 15 mins by immunostaining based FACS assay
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 383.42, ALogP 2.54, HBA 9, HBD 0, PSA 113.41, QED 0.53
Compound (SMILES): C=CCCn1cc(-c2cnc(C)c(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: KQBSVASSAQIRTH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Inhibition of recombinant His-tagged BRD9 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 392.46, ALogP 2.75, HBA 5, HBD 1, PSA 80.22, QED 0.68
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)NCc1ccc(F)cc1
InChIKey: MAZVIKQKJJSOBO-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 326.4, ALogP 4.19, HBA 3, HBD 1, PSA 41.99, QED 0.78
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1cc(Cl)ccc1Cl
InChIKey: HJHPMKAERBOCJC-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 4752.2 nM (pChEMBL 5.320000171661377)
Descriptors: MW 428.3, ALogP 3.27, HBA 5, HBD 1, PSA 102.06, QED 0.81
Compound (SMILES): Cc1ccc(C)c2oc(-c3nc(-c4ccc(C(=O)O)cc4)no3)cc12
InChIKey: AVCXUODHLRZJJP-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 334.33, ALogP 4.46, HBA 5, HBD 1, PSA 89.36, QED 0.59
Compound (SMILES): Cc1cccc(Nc2cc(Br)nc(SCC(=O)O)n2)c1C
InChIKey: OBSVFENGTCLUJY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human Gal4-fused PPARgamma LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 13200 nM (pChEMBL 4.880000114440918)
Descriptors: MW 368.26, ALogP 3.78, HBA 5, HBD 2, PSA 75.11, QED 0.48
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3)cc(NC[C@@H]3CCNC[C@H]3O)nc12
InChIKey: YCVGLKWJKIKVBI-PKOBYXMFSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 394.52, ALogP 2.85, HBA 7, HBD 4, PSA 86.51, QED 0.49
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)c2ccc(-c3ccnc(F)c3)cc2)c1
InChIKey: JEFRBITWIOXMNQ-CQSZACIVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of C-terminal 4His-tagged CYP3A4 (unknown origin) expressed in Escherichia coli by spectrophotometric analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 350.39, ALogP 4.39, HBA 3, HBD 1, PSA 51.22, QED 0.69
Compound (SMILES): Cn1cc(-c2ccc(N3CCC(C4c5c(F)cccc5-c5cncn54)CC3)cc2)cn1
InChIKey: UJGQDAMZVUNFBQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate measured after 10 mins in presence of NADPH by UHPLC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.5, ALogP 4.91, HBA 5, HBD 0, PSA 38.88, QED 0.48
Compound (SMILES): CCN(CC)CCNC(=O)Nc1nc2ccc(Sc3nnc4ccc(-c5ccc(F)cc5)nn34)cc2s1
InChIKey: KWWVEGSNWIJWMP-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of phosphorylated MET Y1230H mutant (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 = 864 nM (pChEMBL 6.059999942779541)
Descriptors: MW 536.66, ALogP 5.15, HBA 9, HBD 2, PSA 100.34, QED 0.27
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4ccnc(NCC5(F)CCNCC5)c4c3)nnc21
InChIKey: FDOTVWCTNRPFBV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 using EAIYAAPFAKKK as substrate incubated for 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.51, ALogP 2.67, HBA 9, HBD 2, PSA 92.5, QED 0.49
Compound (SMILES): CC1(C)CCN1Cc1cccc(F)c1CNc1cc(F)c(S(=O)(=O)Nc2cscn2)c(F)c1
InChIKey: GFSUVQOECDPIQJ-UHFFFAOYSA-N
Target: SCN9A/SCN1B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07699
Assay: Inhibition of recombinant human full length Nav1.7 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -60 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 664 nM (pChEMBL 6.179999828338623)
Descriptors: MW 496.58, ALogP 4.96, HBA 6, HBD 2, PSA 74.33, QED 0.46
Compound (SMILES): NS(=O)(=O)c1cccc(-c2nnc(-c3ccc(Cl)cc3)o2)c1
InChIKey: WSFBXXSBCRXLBR-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A expressed in insect cells microsomes assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence spectrophotometry analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 335.77, ALogP 2.7, HBA 5, HBD 1, PSA 99.08, QED 0.79
Compound (SMILES): O=Cc1ccccc1OCc1cn(CCCOc2ccc3ccc(=O)oc3c2)nn1
InChIKey: GWUGLVXCZLBLLW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow assay
Measurement: Ki = 60.9 nM (pChEMBL 7.210000038146973)
Descriptors: MW 405.41, ALogP 3.25, HBA 8, HBD 0, PSA 96.45, QED 0.24
Compound (SMILES): Nc1nc(NCc2ccccc2)nc(-c2cccc(CO)c2)n1
InChIKey: RVKAHYFWSKSSQQ-UHFFFAOYSA-N
Target: G-protein coupled receptor 68 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15743
Assay: Positive allosteric modulator activity at GPR68 expressed in human HEK293T cells assessed as cAMP production in presence of H+ proton by Split-luciferase based luminescence counter analysis (Rvb = 6.53 to 6.72 No_unit)
Measurement: EC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 307.36, ALogP 2.23, HBA 6, HBD 3, PSA 96.95, QED 0.67
Compound (SMILES): COc1ccccc1CCN1CCn2c(nc3c2c(=O)n(C)c(=O)n3C)C1
InChIKey: GGGDVUYICNEVIX-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human A3 receptor expressed in CHO cell membrane by liquid scintillation counting method relative to control
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 369.43, ALogP 0.5, HBA 8, HBD 0, PSA 74.29, QED 0.67
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cnc2[nH]ccc2c1
InChIKey: ZHODCCQNWOBJHY-ATVHPVEESA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 492.5, ALogP 6.53, HBA 4, HBD 2, PSA 79.9, QED 0.33
Compound (SMILES): COc1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: DYNWEDRLLZIBOF-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human recombinant N-terminal GST-tagged CDK6 (M1-A326 residues) and His6 tagged Cyclin D3 (M1-L292 residues) expressed in sf9 cells using histone H1 (GGGPATPKKAKKL) as substrate incubated for 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 255.32, ALogP 3.11, HBA 4, HBD 1, PSA 47.04, QED 0.92
Compound (SMILES): Cc1cccc2c1B(O)OC(c1ccc(C(=N)N)c(OCc3cccnc3)c1)C2.Cl
InChIKey: LQXAUZRGEUWLRB-UHFFFAOYSA-N
Target: Kallikrein-8 (SINGLE PROTEIN), Homo sapiens
UniProt: O60259
Assay: Inhibition of recombinant human C-terminal 10-His-tagged KLK8 (Gln29 to Gly260 residues) expressed in mouse NS0 cells using BOC-VPR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 387.25
Compound (SMILES): CC(CNC(=O)Nc1ccc(C(C)(C)C)cc1)CN(C)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: PFYPVZCYAJWGGR-QRQSEGCHSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of EHMT2 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 526.64, ALogP 1.71, HBA 10, HBD 5, PSA 163.68, QED 0.29
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1OC
InChIKey: RNFXHTFBTWGHHQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of [3H]cAMP binding to recombinant human His-Tb fused PDE4D2 (86 to 413 residues) expressed in Escherichia coli using [3H]cAMP as substrate preincubated for 10 mins followed by [3H]cAMP addition and measured after 1 hr by scintillation proximity assay
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 367.38, ALogP 3.47, HBA 6, HBD 3, PSA 88.17, QED 0.62
Compound (SMILES): C[C@]1(c2cc(NC(=O)c3ccc(Cl)cn3)cc(F)c2F)N=C(N)S[C@H]2C[C@H]21
InChIKey: GPAXGFDBMSTBMT-RHXQLXPWSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 408.86, ALogP 3.93, HBA 5, HBD 2, PSA 80.37, QED 0.81
Compound (SMILES): O=C(Cn1c(=O)[nH]c2ncc(-c3cccc(C(F)(F)F)c3)cc21)NC1CC1
InChIKey: HNKBEWDWWSYVSP-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Negative allosteric modulation of recombinant human GluN1a/GluN2B expressed in CHO-T-REx cells assessed as inhibition of glutamate/glycine-induced response preincubated for 5 mins followed by glutamate/glycine addition and measured after 5 mins by calcium 5 dye based FLIPR TETRA analysis
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 376.34, ALogP 2.69, HBA 4, HBD 2, PSA 79.78, QED 0.73
Compound (SMILES): CCNc1nc2ccc(Sc3nnc4ccc(-c5ccc(F)cc5)nn34)cc2s1
InChIKey: FXSAUUNZLUWLRE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of phosphorylated MET Y1230H mutant (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.51, ALogP 5.12, HBA 8, HBD 1, PSA 68, QED 0.42
Compound (SMILES): CC(C)S(=O)(=O)c1cc(C(C)(C)C)cc(S(=O)(=O)c2ccc(CN)s2)c1
InChIKey: CPPRLQCSUVFPST-UHFFFAOYSA-N
Target: Arachidonate 12-lipoxygenase (SINGLE PROTEIN), Sus scrofa
UniProt: P16469
Assay: LOX Enzyme Activity Assay: LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls:0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix:Volume Reagent 1 x plate 2 x plate Final ConcnAssay Buffer  2 ml    3 ml 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM20 mM Amplex Red 10 μl   15 μl 100 μM1000 U/ml HRP 10 μl   15 μl   35 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader:Excitation wavelength: 545 nmEmission wavelength: 585 nmHRP Counter Assay Protocol
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 415.6, ALogP 3.52, HBA 6, HBD 1, PSA 94.3, QED 0.81
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)C(C)C)[C@@H](C)O
InChIKey: UFUXIPADWDHAOE-JHKJEGEHSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha2beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 4360 nM (pChEMBL 5.360000133514404)
Descriptors: MW 3360.72
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(NCc3ccc(C(=O)NO)cc3)c2c(=O)n1-c1ccccc1
InChIKey: KMLOBYCAJVUHKQ-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 562.59, ALogP 3.12, HBA 12, HBD 6, PSA 209.89, QED 0.12
Compound (SMILES): Nc1nc2ccc(C(=O)NCc3ccccc3N)cc2s1
InChIKey: ZBSMRRNLVFVMSL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 298.37, ALogP 2.39, HBA 5, HBD 3, PSA 94.03, QED 0.65
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)c2ccc(-c3ccncn3)cc2)c1
InChIKey: MBRVCJRFWYHVHE-CQSZACIVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of C-terminal 4His-tagged CYP3A4 (unknown origin) expressed in Escherichia coli by spectrophotometric analysis
Measurement: IC50 = 19600 nM (pChEMBL 4.710000038146973)
Descriptors: MW 333.39, ALogP 3.64, HBA 4, HBD 1, PSA 64.11, QED 0.77
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4cccc(Br)c4)C3)cc2oc1=O
InChIKey: VMOZXXDRTUKKLO-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured for 5 mins by spectrophotometric Ellman's method
Measurement: IC50 = 3230 nM (pChEMBL 5.489999771118164)
Descriptors: MW 456.38, ALogP 5.46, HBA 4, HBD 0, PSA 42.68, QED 0.48
Compound (SMILES): C[C@H](NC(=O)c1nc(-c2ncc(-c3ccccc3)s2)sc1C1CC1)c1ccc(C(=O)NO)cc1
InChIKey: SELDFFFQCMDDJR-AWEZNQCLSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant N-terminal GST-tagged full length human HDAC5 expressed in baculovirus infected Sf9 cells using Ac-Leu-Gly-Lys(Tfa)-AMC as substrate after 24 hrs by fluorescence based assay
Measurement: IC50 = 16740 nM (pChEMBL 4.78000020980835)
Descriptors: MW 490.61, ALogP 5.42, HBA 7, HBD 3, PSA 104.21, QED 0.24
Compound (SMILES): C=CC(=O)N1CCCC(n2nc(-c3cc(N4CCOCC4)n(C)n3)c3c(N)ncnc32)C1
InChIKey: OSPBHLWSQHFCKU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 catalytic domain (809 to 1153+9 residues) expressed in baculovirus expression system using TK-biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 437.51, ALogP 1, HBA 10, HBD 1, PSA 120.22, QED 0.6
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C1CC1
InChIKey: HQAFQRVIFUNAKT-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of DYRK2 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 280.34, ALogP 2.3, HBA 6, HBD 2, PSA 95.64, QED 0.75
Compound (SMILES): N#Cc1ccc(C(=O)NCc2cccc(Cn3cnc4ccccc43)c2)cc1
InChIKey: LFSPEEMMTVMDAK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human DAN-G cells assessed as reduction in L-Kyn level measured after 48 hrs by HPLC analysis
Measurement: IC50 = 1940 nM (pChEMBL 5.710000038146973)
Descriptors: MW 366.42, ALogP 3.89, HBA 4, HBD 1, PSA 70.71, QED 0.58
Compound (SMILES): O=C(O)C[C@H]1CCCN(C[C@@H](O)c2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: YBQLZPRLWZZECJ-OXQOHEQNSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 542.51, ALogP 5.3, HBA 8, HBD 2, PSA 125.72, QED 0.31
Compound (SMILES): S=C(NCc1ccccc1)NNc1c2c(nc3ccccc13)CCCC2
InChIKey: GHGXCYPXBDQVRC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of recombinant human AChE assessed as dissociation constant using acetylthiocholine iodide as substrate incubated for 10 mins by Ellman's method
Measurement: Ki = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 362.5, ALogP 4.1, HBA 3, HBD 3, PSA 48.98, QED 0.48
Compound (SMILES): O=C(O)CC1CNC=N1
InChIKey: XXSINOSGBVIRNZ-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSD5
Assay: Inhibition of human GAT2 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 128.13, ALogP -0.54, HBA 3, HBD 2, PSA 61.69, QED 0.52
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)NC4CCCCC4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RAJUTZRXBLKGIB-JYFAEEROSA-N
Target: Trypsin (SINGLE PROTEIN), Sus scrofa
UniProt: P00761
Assay: Inhibition of porcine trypsin using Mes-DArg-Gly-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 829.04, ALogP 1.97, HBA 9, HBD 8, PSA 230.95, QED 0.12
Compound (SMILES): Cc1ccc(CSc2nnc(-c3ccccn3)n2Cc2ccco2)cc1C(F)(F)F
InChIKey: OQJGZGAYSCWFCK-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in human U2OS cells co-transfected with GFP and beta-arrestin-2 assessed as increase in beta-arrestin-2 recruitment after 20 mins by Hoechst staining-based assay
Measurement: EC50 = 3138 nM (pChEMBL 5.5)
Descriptors: MW 430.46, ALogP 5.6, HBA 6, HBD 0, PSA 56.74, QED 0.37
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)C(F)(F)F)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: XQSWNESGOFOJLG-HJJAOGADSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant human SIRT2 deacylation activity expressed in Escherichia coli Rosetta2 using Fluor-de-Lys-SIRT2 deacetylase substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 871.96, ALogP -1.71, HBA 10, HBD 14, PSA 361.72, QED 0.03
Compound (SMILES): Nc1nc2ccc(C(=O)NCc3ccc(Cl)c(Cl)c3)cc2s1
InChIKey: JOBYYAUGFMYSBN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 352.25, ALogP 4.12, HBA 4, HBD 2, PSA 68.01, QED 0.75
Compound (SMILES): Cc1ccc2nc(CSc3nnc(NC(=O)Nc4cccc(C(F)(F)F)c4)s3)cc(=O)n2c1
InChIKey: OQDBRNRNKHKMSL-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 9280 nM (pChEMBL 5.03000020980835)
Descriptors: MW 492.51, ALogP 4.81, HBA 8, HBD 2, PSA 101.28, QED 0.31
Compound (SMILES): Cc1cc(N2CC(C(=O)NN)CC2=O)c(Cl)c(C)c1S(N)(=O)=O
InChIKey: ZZBVZOGPOHYKDO-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human CA7 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 360.82, ALogP -0.05, HBA 5, HBD 3, PSA 135.59, QED 0.39
Compound (SMILES): C[C@@H]1CC(c2cnc3c(C#N)nn([C@H](C)c4ccc(Cl)cc4Cl)c3n2)=CC[C@@H]1N1CCC[C@H]1CO
InChIKey: KQZLRWGGWXJPOS-NLFPWZOASA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.46, ALogP 5.25, HBA 7, HBD 1, PSA 90.86, QED 0.5
Compound (SMILES): O=C(O)CN1C(=O)/C(=C/c2cccc(OCCc3ccccc3)c2)SC1=S
InChIKey: STKZJPQZNBVHCZ-ATVHPVEESA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15121
Assay: Uncompetitive inhibition of human recombinant aldose reductase expressed in Escherichia coli BL21(DE3)pLysS assessed as dissociation constant of enzyme-inhibitor-substrate complex using L-idose as substrate by Morrison's plot analysis
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 399.49, ALogP 3.59, HBA 5, HBD 1, PSA 66.84, QED 0.57
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)C2CCCCC2)cc1Cl
InChIKey: XESFZDLAWXFOQS-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 424.93, ALogP 0.82, HBA 6, HBD 3, PSA 143.63, QED 0.62
Compound (SMILES): CS(=O)(=O)Nc1ccc2oc(-c3ccccc3)nc2c1
InChIKey: MEFGMEZNBFFZJC-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 288.33, ALogP 2.87, HBA 4, HBD 1, PSA 72.2, QED 0.8
Compound (SMILES): C=CCCn1cc(-c2cncc(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: QAORWPLEPWLSPU-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Inhibition of recombinant His-tagged CECR2 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 378.43, ALogP 2.44, HBA 5, HBD 1, PSA 80.22, QED 0.69
Compound (SMILES): CCc1cc(Cl)c(OC)c(N2CCN(CCCCNC(=O)c3cc4ccccc4o3)CC2)c1
InChIKey: NIENYVQCIJZKMD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from 5-HT1A receptor (unknown origin)
Measurement: Ki = 560 nM (pChEMBL 6.25)
Descriptors: MW 470.01, ALogP 4.99, HBA 5, HBD 1, PSA 57.95, QED 0.45
Compound (SMILES): Cn1cc(-c2cn3nccc3c(-c3cnn([C@]4(CC#N)C[C@@H](C#N)C4)c3)n2)cn1
InChIKey: XPLZTJWZDBFWDE-OYOVHJISSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 signaling pathway in human whole blood lymphocytes assessed as reduction in IFN-alpha induced STAT3 phosphorylation preincubated for 45 mins followed by IFN-alpha addition and measured measured after 15 mins by FACS assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 383.42, ALogP 2.54, HBA 9, HBD 0, PSA 113.41, QED 0.53
Compound (SMILES): C=CCCn1cc(-c2cnc(C)c(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: KQBSVASSAQIRTH-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Inhibition of recombinant His-tagged CECR2 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 392.46, ALogP 2.75, HBA 5, HBD 1, PSA 80.22, QED 0.68
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)NCc1ccc(F)cc1
InChIKey: MAZVIKQKJJSOBO-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as decrease in CP55940-induced beta-arrestin recruitment pretreated with non-selective cannabinoid receptor agonist CP55940 for 30 mins and measured after 20 mins by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 326.4, ALogP 4.19, HBA 3, HBD 1, PSA 41.99, QED 0.78
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1cc(Cl)ccc1Cl
InChIKey: HJHPMKAERBOCJC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 12.4 nM (pChEMBL 7.909999847412109)
Descriptors: MW 428.3, ALogP 3.27, HBA 5, HBD 1, PSA 102.06, QED 0.81
Compound (SMILES): Cc1ccc(C)c2oc(-c3nc(-c4ccc(C(=O)O)cc4)no3)cc12
InChIKey: AVCXUODHLRZJJP-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 334.33, ALogP 4.46, HBA 5, HBD 1, PSA 89.36, QED 0.59
Compound (SMILES): Cc1cccc(Nc2cc(Br)nc(SCC(=O)O)n2)c1C
InChIKey: OBSVFENGTCLUJY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human Gal4-fused PPARdelta LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 368.26, ALogP 3.78, HBA 5, HBD 2, PSA 75.11, QED 0.48
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3)cc(NC[C@@H]3CCNC[C@H]3O)nc12
InChIKey: YCVGLKWJKIKVBI-PKOBYXMFSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 32100 nM (pChEMBL 4.489999771118164)
Descriptors: MW 394.52, ALogP 2.85, HBA 7, HBD 4, PSA 86.51, QED 0.49
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)c2ccc(-c3ccnc(F)c3)cc2)c1
InChIKey: JEFRBITWIOXMNQ-CQSZACIVSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant N-terminal GST-tagged human ROCK2 (5 to 554 residues) expressed in baculovirus infected Sf9 cells using S6K as substrate incubated for 30 mins in presence of ATP by ADP Glo kinase assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 350.39, ALogP 4.39, HBA 3, HBD 1, PSA 51.22, QED 0.69
Compound (SMILES): Cn1cc(-c2ccc(N3CCC(C4c5c(F)cccc5-c5cncn54)CC3)cc2)cn1
InChIKey: UJGQDAMZVUNFBQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using s-mephenytoin as substrate measured after 10 mins in presence of NADPH by UHPLC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.5, ALogP 4.91, HBA 5, HBD 0, PSA 38.88, QED 0.48
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4ccnc(NCC5(F)CCNCC5)c4c3)nnc21
InChIKey: FDOTVWCTNRPFBV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG incubated for 1 hr by Fluorescence polarization binding assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 448.51, ALogP 2.67, HBA 9, HBD 2, PSA 92.5, QED 0.49
Compound (SMILES): CC1(C)CCN1Cc1cccc(F)c1CNc1cc(F)c(S(=O)(=O)Nc2cscn2)c(F)c1
InChIKey: GFSUVQOECDPIQJ-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at PXR in human DPX2 cells after 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 11800 nM (pChEMBL 4.929999828338623)
Descriptors: MW 496.58, ALogP 4.96, HBA 6, HBD 2, PSA 74.33, QED 0.46
Compound (SMILES): NS(=O)(=O)c1cccc(-c2nnc(-c3ccc(Cl)cc3)o2)c1
InChIKey: WSFBXXSBCRXLBR-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in insect cells microsomes assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence spectrophotometry analysis
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 335.77, ALogP 2.7, HBA 5, HBD 1, PSA 99.08, QED 0.79
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cnc2[nH]ccc2c1
InChIKey: ZHODCCQNWOBJHY-ATVHPVEESA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 407 nM (pChEMBL 6.389999866485596)
Descriptors: MW 492.5, ALogP 6.53, HBA 4, HBD 2, PSA 79.9, QED 0.33
Compound (SMILES): COc1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: DYNWEDRLLZIBOF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant full length N-terminal GST His6 fused CDK9 (M1 to F372 residues/ N-terminal His6 tagged Cyclin T1 (M1 to K726 residues) expressed in sf9 cells using RBER-IRStide as substrate incubated for 90 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 255.32, ALogP 3.11, HBA 4, HBD 1, PSA 47.04, QED 0.92
Compound (SMILES): Cc1cccc2c1B(O)OC(c1ccc(C(=N)N)c(OCc3cccnc3)c1)C2.Cl
InChIKey: LQXAUZRGEUWLRB-UHFFFAOYSA-N
Target: Kallikrein-14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0G3
Assay: Inhibition of recombinant human C-terminal 10-His-tagged KLK14 (Q19 to M248 residues) expressed in mouse NS0 cells using BOC-VPR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 387.25
Compound (SMILES): O=C(Cn1c(=O)[nH]c2ncc(-c3cccc(C(F)(F)F)c3)cc21)NC1CC1
InChIKey: HNKBEWDWWSYVSP-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13224
Assay: Standard cell-based calcium flux assay: NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2, 0.5 mM MgCl2 (standard assay) or 1.5 mM MgCl2 (HTS assay), 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 2 mM CaCl2, 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to EC40 (standard assay) is used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 376.34, ALogP 2.69, HBA 4, HBD 2, PSA 79.78, QED 0.73
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)C(C)C)[C@@H](C)O
InChIKey: UFUXIPADWDHAOE-JHKJEGEHSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Antagonist activity at human alpha9alpha10 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 3360.72
Compound (SMILES): Nc1nc2ccc(C(=O)NCc3ccccc3N)cc2s1
InChIKey: ZBSMRRNLVFVMSL-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 298.37, ALogP 2.39, HBA 5, HBD 3, PSA 94.03, QED 0.65
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4cccc(Br)c4)C3)cc2oc1=O
InChIKey: VMOZXXDRTUKKLO-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured for 5 mins by spectrophotometric Ellman's method
Measurement: IC50 = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 456.38, ALogP 5.46, HBA 4, HBD 0, PSA 42.68, QED 0.48
Compound (SMILES): C[C@H](NC(=O)c1nc(-c2ncc(-c3ccccc3)s2)sc1C1CC1)c1ccc(C(=O)NO)cc1
InChIKey: SELDFFFQCMDDJR-AWEZNQCLSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human N-terminal GST-tagged HDAC7 (518 to end residues) expressed in baculovirus infected Sf9 cells using Ac-Leu-Gly-Lys(Tfa)-AMC as susbtrate after 24 hrs by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 490.61, ALogP 5.42, HBA 7, HBD 3, PSA 104.21, QED 0.24
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C1CC1
InChIKey: HQAFQRVIFUNAKT-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of wild type full length DYRK1A (unknown origin) in human U2OS cells assessed as reduction in pSER520 autophosphorylation incubated for 5 hrs by western blot analysis
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 280.34, ALogP 2.3, HBA 6, HBD 2, PSA 95.64, QED 0.75
Compound (SMILES): O=C(O)C[C@H]1CCCN(C[C@@H](O)c2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: YBQLZPRLWZZECJ-OXQOHEQNSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 542.51, ALogP 5.3, HBA 8, HBD 2, PSA 125.72, QED 0.31
Compound (SMILES): S=C(NCc1ccccc1)NNc1c2c(nc3ccccc13)CCCC2
InChIKey: GHGXCYPXBDQVRC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of recombinant human AChE assessed as dissociation constant for enzyme-substrate-inhibitor complex using acetylthiocholine iodide as substrate incubated for 10 mins by Ellman's method
Measurement: Ki = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 362.5, ALogP 4.1, HBA 3, HBD 3, PSA 48.98, QED 0.48
Compound (SMILES): O=C(O)CC1CNC=N1
InChIKey: XXSINOSGBVIRNZ-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P48066
Assay: Inhibition of human GAT3 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 128.13, ALogP -0.54, HBA 3, HBD 2, PSA 61.69, QED 0.52