lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NCc1ncc(C(F)(F)F)cc1Cl)c1ccc2c(c1)C1(CCS(=O)(=O)CC1)[C@H](C1CC1)N2S(=O)(=O)c1ccc(F)cc1
InChIKey: PZGSYNNVPNLHQG-SANMLTNESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Inhibition of Tag-lite green-labeled agonist binding to terbium fluorophore-labeled human N-terminal SNAP-tag GnRh receptor expressed in HEK293 cells by TR-FRET assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 672.12, ALogP 5.26, HBA 6, HBD 1, PSA 113.51, QED 0.36
Compound (SMILES): Cc1cc2cc(n1)-c1cnn(C)c1OCCC[C@@H](C)CN1/C(=N/C2=O)Nc2ccc(CN3CCN(C)CC3)cc21
InChIKey: AIQBYZOTCIQTGW-HXUWFJFHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) Del19 mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 542.69, ALogP 3.77, HBA 9, HBD 1, PSA 91.12, QED 0.52
Compound (SMILES): CO[C@H]1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3nc(N)n[nH]3)CC2)C1
InChIKey: CWVKUWZSIMMEOV-IRXDYDNUSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse acidic mammalian chitinase expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.81
Compound (SMILES): Cc1cc(-c2cnc3ccn(CC4CCC4)c3c2)ccc1F
InChIKey: MTXPFYDPXWYSJL-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 294.37, ALogP 4.95, HBA 2, HBD 0, PSA 17.82, QED 0.67
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nnc(-c3nnc(SCC(=O)c4ccc(F)cc4)[nH]3)c2-c2ccccc2)cc1
InChIKey: HBLHNVJAWVVDJO-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as reduction in CO2 hydration incubated for 1 hr by phenol red staining-based stopped flow assay
Measurement: Ki = 102.3 nM (pChEMBL 6.989999771118164)
Descriptors: MW 535.59, ALogP 3.48, HBA 9, HBD 2, PSA 149.51, QED 0.23
Compound (SMILES): O=C(Nc1ccc(Oc2ccc(F)cc2)cc1)N1CCc2ncccc2[C@@H]1c1ccc(Cl)cc1
InChIKey: FMQWOAKTQPLQBR-SANMLTNESA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human follicle stimulating hormone receptor assessed as reduction in agonist-induced cAMP production preincubated for 20 mins followed by agonist solution addition and measured after 120 mins by cell based TR-FRET assay
Measurement: IC50 > 16000 nM (pChEMBL 4.796000003814697)
Descriptors: MW 473.94, ALogP 6.85, HBA 3, HBD 1, PSA 54.46, QED 0.35
Compound (SMILES): CC(C)n1nc(-c2ccc3oc(N)nc3c2)c2c(F)nc(N)nc21
InChIKey: XYFXUNWLLFSAGS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of human recombinant GST-tagged mTOR catalytic domain (1360 to 2549 residues) expressed in baculovirus expression system using GFP-4E-BP1 peptide as substrate incubated for 1 hr by LanthaScreen assay
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 327.32, ALogP 2.52, HBA 8, HBD 2, PSA 121.67, QED 0.54
Compound (SMILES): O=C(c1cc2ccccc2[nH]1)N1CCN(CCOc2cccnc2)CC1
InChIKey: WJOFBCYZALIRKI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: D2 DAR Beta-Arrestin Recruitment Assay: For a secondary-screen and selectivity assays, DAR PathHunter® βarrestin GPCR cell lines from DiscoverX (Fremont, Calif.) were used. In the D2 Receptor PathHunter® β-arrestin GPCR cell line, the D2 DAR is overexpressed and fused with a small 42-amino acid fragment of β-galactosidase called ProLink on a CHO cellular background expressing a fusion protein of β-arrestin and a larger N-terminal deletion mutant of β-galactosidase (enzyme acceptor). When DAR is activated by dopamine, it stimulates binding of β-arrestin to the ProLink-tagged DAR and the two complementary parts of β-galactosidase form a functional enzyme. When substrate (PathHunter Detection reagent) is added, β-galactosidase hydrolyzes it and generates a chemiluminescent signal.
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 350.42, ALogP 2.4, HBA 4, HBD 1, PSA 61.46, QED 0.77
Compound (SMILES): CN1C(=O)C(O)(CC(=O)c2ccc3ccccc3c2)c2ccccc21
InChIKey: SDEIDCCPKCHFSQ-UHFFFAOYSA-N
Target: Chromobox protein homolog 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95931
Assay: Binding affinity to recombinant human N-terminal GST-tagged CBX7 (1 to 62 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 331.37, ALogP 3.28, HBA 3, HBD 1, PSA 57.61, QED 0.75
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)c(F)c(C(=O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: NZZQNOHKPCQKKC-IEBWSBKVSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 535.57, ALogP 3.81, HBA 7, HBD 4, PSA 158.41, QED 0.08
Compound (SMILES): O=c1cc(NCCc2ccc(Cl)cc2)[nH]c(=O)[nH]1
InChIKey: JSUODDTVALGQAK-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as induction of beta-arrestin recruitment by luminescence assay
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 265.7, ALogP 1.37, HBA 3, HBD 3, PSA 77.75, QED 0.78
Compound (SMILES): COc1ccc2cnn(-c3ccc(S(N)(=O)=O)cc3)c(=O)c2c1OC
InChIKey: FOQCIXFYYOJQMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human cytosolic CA 1 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 90.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 361.38, ALogP 1.05, HBA 7, HBD 1, PSA 113.51, QED 0.74
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCC5(CNCCO5)C4)cc3)sc2n1
InChIKey: YFNCJZDINCZFFH-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 451.6, ALogP 2.73, HBA 7, HBD 3, PSA 92.51, QED 0.55
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cn[nH]c1
InChIKey: VFHRALAVCKZLHR-GDNBJRDFSA-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 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 442.44, ALogP 5.37, HBA 4, HBD 2, PSA 79.9, QED 0.56
Compound (SMILES): Nc1nc2[nH]c(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1
InChIKey: VEKHZPVGFDPVJG-HNNXBMFYSA-N
Target: Proton-coupled folate transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NT5
Assay: Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells assessed as antiproliferative activity measured as reduction in cell growth after 96 hrs by Cell-Titer Blue assay
Measurement: IC50 = 3.82 nM (pChEMBL 8.420000076293945)
Descriptors: MW 459.43, ALogP 1.2, HBA 6, HBD 6, PSA 191.26, QED 0.26
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell Assay: Inhibition of RSK phosphorylation (pRSK with 40%  mouse serum )
Measurement: IC50 = 788 nM (pChEMBL 6.099999904632568)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): CCCCCn1cc(C(=O)NC(C)(C)c2ccccc2)c2cccnc21
InChIKey: CAEILFVPDJUERU-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in AtT-20 cells measured every 2 secs for 2 mins by FLIPR assay
Measurement: EC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 349.48, ALogP 4.89, HBA 3, HBD 1, PSA 46.92, QED 0.62
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O)C(C)C
InChIKey: CJLWXPSNKINPJW-FCRYVSRXSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Full agonist activity at mouse MC5R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 627.14, ALogP 0.72, HBA 6, HBD 5, PSA 193.79, QED 0.22
Compound (SMILES): CC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O
InChIKey: LZEMTIAYLKCDHP-GWMMUDDPSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q01727
Assay: Full agonist activity at mouse MC1R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 756.6, ALogP -0.02, HBA 7, HBD 6, PSA 222.47, QED 0.12
Compound (SMILES): CCCN(CCCCCc1ccc(O)c(O)c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: TXJZKUBFJGPDAH-FQEVSTJZSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3 dopamine receptor expressed in CHO cells by [35S]GTPgammaS binding assay
Measurement: EC50 = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 383.53, ALogP 4.79, HBA 4, HBD 3, PSA 63.93, QED 0.43
Compound (SMILES): Nc1nc(C(=O)N/N=C/c2ccc(F)cc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: BYMPLOLXBMGRPW-AWQFTUOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 403.4, ALogP 0.4, HBA 8, HBD 3, PSA 158.35, QED 0.41
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: LPATVOINCAVXRL-NTBYCYSFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 1005.19
Compound (SMILES): COc1c(C(N)=O)csc1-c1cncc(-c2ccc(N3CCNCC3)cc2)c1C
InChIKey: JBXIPHYYFNQDOC-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) expressed in HEK293 cells transfected with CAGA-luciferase and Renilla luciferase reporter measured after 24 hrs by dual luciferase reporter assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 408.53, ALogP 3.3, HBA 6, HBD 2, PSA 80.48, QED 0.68
Compound (SMILES): COc1ccc(C(/C=C\CN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2)c2ccc(OC)cc2)cc1
InChIKey: RNLUGOUUDNQOGZ-IPKBDRFQSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 10232.93 nM (pChEMBL 4.989999771118164)
Descriptors: MW 501.62, ALogP 5.4, HBA 5, HBD 1, PSA 68.23, QED 0.3
Compound (SMILES): O=c1cc(NCCCN2CCN(c3nc(Cl)cc4ccccc34)CC2)c2ccccc2o1
InChIKey: WDZOHXJSHKRGTL-UHFFFAOYSA-N
Target: DNA topoisomerase 4 subunit A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0C1U9
Assay: Inhibition of Staphylococcus aureus ATCC 29213 DNA topoisomerase 4 subunit ParC assessed as reduction in decatenation of kinetoplast DNA incubated for 30 mins by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 10200 nM (pChEMBL 4.989999771118164)
Descriptors: MW 448.95, ALogP 4.62, HBA 6, HBD 1, PSA 61.61, QED 0.26
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(c5ccc(O)c(Cl)c5)CC4)cc3)[nH]c2c1=O
InChIKey: OSURRZXGJWBWBW-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from recombinant human A3 adenosine receptor expressed in CHO cell membranes measured after 45 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 545.02, ALogP 2.36, HBA 8, HBD 3, PSA 144.39, QED 0.34
Compound (SMILES): COC(=O)[C@@H]1CC(=O)N(c2ccc(OC)cc2)[C@H]1c1ccc(S(N)(=O)=O)cc1
InChIKey: JIXJQYLYFCMQJV-AEFFLSMTSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 43.3 nM (pChEMBL 7.360000133514404)
Descriptors: MW 404.44, ALogP 1.61, HBA 6, HBD 1, PSA 116, QED 0.76
Compound (SMILES): O=P(O)(O)Oc1cc(OP(=O)(O)O)c(OP(=O)(O)O)cc1OP(=O)(O)O
InChIKey: OFSQKFMVBPORNX-UHFFFAOYSA-N
Target: Inositol polyphosphate-5-phosphatase A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14642
Assay: Inhibition of recombinant human brain INPP5A expressed in Escherichia coli incubated for 10 mins by malachite green reagent based phosphate assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 462.03, ALogP -0.43, HBA 8, HBD 8, PSA 267.04, QED 0.23
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NC2CCCCC2)c([S+]([O-])Cc2ccccc2)cc1Cl
InChIKey: JLKREKAPCORGQO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 455, ALogP 3.36, HBA 4, HBD 2, PSA 112.32, QED 0.65
Compound (SMILES): Nc1nc(C(=O)NNC(=O)Nc2ccc(Cl)cc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: USLTWVODMNCJML-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 48.2 nM (pChEMBL 7.320000171661377)
Descriptors: MW 450.87, ALogP 0.62, HBA 8, HBD 5, PSA 187.12, QED 0.36
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: MFMVYBPYDSNLTE-LWMCYQQMSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12392
Assay: Inhibition of rat alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 1650.92
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](C)c1cccc(Cc2ccccc2)c1.O=C(O)C(F)(F)F
InChIKey: QXCKSQSCFNLQCL-UFABNHQSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Agonist activity at rat Mu-type opioid receptor expressed in rat C6 cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 1 hr by liquid scintillation counting method
Measurement: EC50 = 44.4 nM (pChEMBL 7.349999904632568)
Descriptors: MW 402.54, ALogP 4.35, HBA 3, HBD 3, PSA 75.35, QED 0.55
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 using RHKKAc-AMC fluorogenic peptide as substrate incubated for 2 hrs by microplate reader assay
Measurement: IC50 = 5720 nM (pChEMBL 5.239999771118164)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): Oc1ccc(/C=N/c2c3c(nc4ccccc24)CCCC3)cc1O
InChIKey: PQHHHZGJZDSJDP-CIAFOILYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE expressed in HEK293 cells using acetylcholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 609 nM (pChEMBL 6.210000038146973)
Descriptors: MW 318.38, ALogP 4.28, HBA 4, HBD 2, PSA 65.71, QED 0.55
Compound (SMILES): COc1cc(N2CCCNC2=O)ccc1Nc1ncc(Cl)c(Nc2ccccc2NC(C)=O)n1
InChIKey: KUFBKQQDUMDVPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of recombinant human N-terminal GST-tagged MET (956 to 1390 residues) cytoplasmic domain expressed in baculovirus expression system using Srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 481.94, ALogP 4.5, HBA 7, HBD 4, PSA 120.51, QED 0.39
Compound (SMILES): CS(=O)(=O)c1ccc(S(=O)(=O)c2ccc(CN)s2)cc1-c1ccccc1
InChIKey: ZTFTYDPCJSMLJQ-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 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 407.54, ALogP 3.11, HBA 6, HBD 1, PSA 94.3, QED 0.7
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3ccc(S(=O)(=O)N4CCN(c5ccc(Cl)cc5)CC4)cc3)nc2n(C)c1=O
InChIKey: HNMAAFCTPZTDQJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Mus musculus
UniProt: Q60614
Assay: Displacement of [3H]PSB-603 from recombinant mouse A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 8.34 nM (pChEMBL 8.079999923706055)
Descriptors: MW 543.05, ALogP 2.66, HBA 8, HBD 1, PSA 113.3, QED 0.4
Compound (SMILES): C=CC(=O)N1CCC[C@H]1COc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: ZJMZNFQDSWTHLP-FQEVSTJZSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Biochemical Enzyme Assay: The inhibitory activity of the present compounds against Btk was assessed in a biochemical enzyme assay. Assay plates in 384 well format were prepared with 8-point serial dilutions for the test compounds on a Thermo CatX workstation equipped with a Innovadyne Nanodrop Express. The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO. The kinase reactions were started by stepwise addition of 4.5 ul per well of peptide/ATP-solution (4 uM FITC-Ahx-TSELKKWALYDYMPMNAND-NH2, 164 uM ATP) in kinase buffer (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% Tween20, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 18 mM MgCl2, 1 mM MnCl2) and 4.5 ul per well of enzyme solution (6.4 nM full-length human recombinant BTK) in kinase buffer. Kinase reactions were incubated at 30° C. for 60 minutes and subsequently terminated by addition of 16 ul per well of stop solution (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35). Kinase reactions were analyzed on a Caliper LC3000 workstation by separating phosphorylated and unphosphorylated peptides and kinase activities were calculated from the amounts of newly formed phospho-peptide. Inhibition data were calculated by comparison to control reactions without enzyme (100% inhibition) and without inhibitors (0% inhibition). The concentration of inhibitor required for 50% inhibition (IC50) was calculated from the inhibition in response to inhibitor concentrations.
Measurement: IC50 < 0.1 nM (pChEMBL 10)
Descriptors: MW 533.58, ALogP 5, HBA 6, HBD 2, PSA 110.44, QED 0.39
Compound (SMILES): O=C(/C=C/c1ccc(OCCCCCCN2CCCC2)cc1)c1ccc(OCCCCCCN2CCCC2)cc1O
InChIKey: HMJSYJOCHJOOKM-HMMYKYKNSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE using butyrylthiocholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 562.8, ALogP 7.36, HBA 6, HBD 1, PSA 62.24, QED 0.11
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCOCCOCCNC(=O)CCCCCN1/C(=C/C=C/C=C/C2=[N+](CCCCS(=O)(=O)[O-])c3ccccc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: BQDLAHRGAQPPJE-WJSZPSLZSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Binding affinity to human neurotensin receptor 1 stably expressed in CHO cells incubated for 60 mins in presence of NT (8 to 13) without compound washout by Hoechst H33342 staining confocal microscopy analysis
Measurement: Kd = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 1658.07
Compound (SMILES): O=C(Cc1ccccc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: YEBWNEBTTYUFMD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 401.51, ALogP 3.69, HBA 4, HBD 1, PSA 58.36, QED 0.71
Compound (SMILES): N=C(N)NCCC[C@H](N)C(=O)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ONIJRTOENNPBIQ-AQUVTFJZSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]-NMS from human muscarinic M5 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 2398.83 nM (pChEMBL 5.619999885559082)
Descriptors: MW 562.72, ALogP 2.51, HBA 6, HBD 6, PSA 169.67, QED 0.13
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4cc(F)ccc42)CSCC3)cc1
InChIKey: LOFPHNPTVBYXBB-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic HDAC substrate
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 356.42, ALogP 3.74, HBA 4, HBD 2, PSA 54.26, QED 0.56
Compound (SMILES): CC(C)(C)Cc1cc(-c2onc([C@@H](CCC(=O)[O-])CC(=O)Nc3ccc(Cl)cc3Cl)c2C2CC2)no1.[Na+]
InChIKey: YEQSGBJZMBCONP-RSAXXLAASA-M
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Time-dependent inhibition of human CYP3A4 using midazolam as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 534.44, ALogP 7.08, HBA 6, HBD 2, PSA 118.46, QED 0.29
Compound (SMILES): CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: NJAYXMBERKCZQC-DHXVBOOMSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant human 5HT2B receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 565 nM (pChEMBL 6.25)
Descriptors: MW 179.24, ALogP 2.09, HBA 1, HBD 1, PSA 12.03, QED 0.75
Compound (SMILES): CCOc1cccc2cc(-c3cc(OC)c(OC)c(OC)c3)c(=O)oc12
InChIKey: NRVCXNQZPYRPDB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of radioligand from human adenosine receptor A2B expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 356.37, ALogP 3.88, HBA 6, HBD 0, PSA 67.13, QED 0.62
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2cccc(Br)c2)n(C)c1=O
InChIKey: GDXNESQVHGSDFC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAOA expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured over 45 mins by horseradish peroxidase-Amplex Red-coupled fluorometric assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 404.27, ALogP 1.61, HBA 7, HBD 0, PSA 65.06, QED 0.65
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human N-terminal GST-tagged FLT3 (564 to end residues) expressed in sf21 cells using biotin labelled Ahx-GGEEEEYFELVKKKK peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 45 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1C(N)=O
InChIKey: FFYLSLMDLCQSRS-UHFFFAOYSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2/JAK2 in IL23-stimulated human Kit225 cells by steady-glo luciferase assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 380.38, ALogP 2.56, HBA 6, HBD 4, PSA 122.03, QED 0.52
Compound (SMILES): NS(=O)(=O)c1ccc(OP(=O)(Sc2ccccc2)c2ccccc2)cc1
InChIKey: KTMXZVZXSJIZEX-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human recombinant carbonic anhydrase 5B preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 28.7 nM (pChEMBL 7.539999961853027)
Descriptors: MW 405.44, ALogP 4.02, HBA 5, HBD 1, PSA 86.46, QED 0.63
Compound (SMILES): O=C(NCc1ncc(C(F)(F)F)cc1Cl)c1ccc2c(c1)C1(CCS(=O)(=O)CC1)[C@H](C1CC1)N2S(=O)(=O)c1ccc(F)cc1
InChIKey: PZGSYNNVPNLHQG-SANMLTNESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Irreversible inhibition of CYP3A4 in human liver microsomes using midazolam as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 672.12, ALogP 5.26, HBA 6, HBD 1, PSA 113.51, QED 0.36
Compound (SMILES): Cc1cc2cc(n1)-c1cnn(C)c1OCCC[C@@H](C)CN1/C(=N/C2=O)Nc2ccc(CN3CCN(C)CC3)cc21
InChIKey: AIQBYZOTCIQTGW-HXUWFJFHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) L858R mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 542.69, ALogP 3.77, HBA 9, HBD 1, PSA 91.12, QED 0.52
Compound (SMILES): CO[C@H]1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3nc(N)n[nH]3)CC2)C1
InChIKey: CWVKUWZSIMMEOV-IRXDYDNUSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full-length C-terminal his-tagged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N\"-triacetylchitotrioside as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.81
Compound (SMILES): CC(=O)Oc1c(C(C)C)cc2c(c1OC(C)=O)-c1cccc3c1[C@@H](C2)N(C)CC3
InChIKey: KFEHEEITVOEJOF-HXUWFJFHSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at D1R (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: EC50 = 954.99 nM (pChEMBL 6.019999980926514)
Descriptors: MW 393.48, ALogP 4.41, HBA 5, HBD 0, PSA 55.84, QED 0.57
Compound (SMILES): Cc1cc(-c2cnc3ccn(CC4CCC4)c3c2)ccc1F
InChIKey: MTXPFYDPXWYSJL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG expressed in HEK293 cell membranes measured after 80 mins by TopCount scintillation analysis
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 294.37, ALogP 4.95, HBA 2, HBD 0, PSA 17.82, QED 0.67
Compound (SMILES): O=C(Nc1ccc(Oc2ccc(F)cc2)cc1)N1CCc2ncccc2[C@@H]1c1ccc(Cl)cc1
InChIKey: FMQWOAKTQPLQBR-SANMLTNESA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P16473
Assay: Antagonist activity at human thyroid stimulating hormone receptor expressed in rat HTC133 cells assessed as reduction in agonist-induced cAMP production preincubated for 20 mins followed by agonist solution addition and measured after 60 mins by cell based TR-FRET assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 473.94, ALogP 6.85, HBA 3, HBD 1, PSA 54.46, QED 0.35
Compound (SMILES): O=C(c1cc2ccccc2[nH]1)N1CCN(CCOc2cccnc2)CC1
InChIKey: WJOFBCYZALIRKI-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: D3 Radioligand Binding Assay: Compounds were tested for their ability to compete with the orthosteric radioligand [3H]methylspiperone for binding to the D3 DAR using stable HEK cell lines expressing the D3 DAR (Codex Biosciences, Gaithersburg, Md., Catalogue no. CB-80300-206) as described in the detailed protocol below presented in Table 5. Cells were cultured in Dulbecco's modified Eagle's Medium (Corning, catalogue no. 10-013) containing 10% FBS, 1,000 units/mL Penicillin, 1,000 mg/mL Streptomycin, 100 mM sodium pyruvate, 1 μg/mL Gentamicin, and 250 mg/mL G418. All cells were maintained at 37° C. in 500 CO2 and 90% humidity. For radioligand binding assays cells were removed mechanically using calcium-free Earle's balanced salt solution (EBSS). Intact cells were collected by centrifugation and then lysed with 5 mM Tris-HCl and 5 mM MgCl2 at pH 7.4. Homogenates were centrifuged at 30,000×g for 30 minutes. The membranes were re-suspended in EBSS (US Biological, catalogue no. E0249-05) pH 7.4 to a concentration of 16 μg/mL. For competition binding studies, membrane preparations were incubated for 90 minutes at room temperature with various concentrations of compound and a single concentration of [3H]methylspiperone (Perkin Elmer, NET856) in a reaction volume of 250 μL. Non-specific binding was determined in the presence of 4 μM (+)-butaclamol (Sigma-Aldrich, catalogue no. D033). Bound ligand was separated from unbound by filtration through GF/C filters using a PerkinElmer cell harvester and quantified on a Top-count (PerkinElmer). Ki values were determined using Cheng-Prusoff equation from observed IC50 values and ligand Kd values from separate saturation experiments.
Measurement: EC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 350.42, ALogP 2.4, HBA 4, HBD 1, PSA 61.46, QED 0.77
Compound (SMILES): O=c1cc(NCCc2ccc(Cl)cc2)[nH]c(=O)[nH]1
InChIKey: JSUODDTVALGQAK-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at human GPR84 expressed in recombinant CHO cells harboring beta-galactosidase fragment assessed as inhibition of forskolin induced cAMP production incubated for 15 mins by radioactive [3H]cAMP based assay
Measurement: EC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 265.7, ALogP 1.37, HBA 3, HBD 3, PSA 77.75, QED 0.78
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cn[nH]c1
InChIKey: VFHRALAVCKZLHR-GDNBJRDFSA-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 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 442.44, ALogP 5.37, HBA 4, HBD 2, PSA 79.9, QED 0.56
Compound (SMILES): Nc1nc2[nH]c(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1
InChIKey: VEKHZPVGFDPVJG-HNNXBMFYSA-N
Target: Reduced folate transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P41440
Assay: Binding affinity to human RFC2 expressed in human HeLa R1-11 cells assessed as antiproliferative activity measured as reduction in cell growth after 96 hrs by Cell-Titer Blue assay
Measurement: IC50 = 507 nM (pChEMBL 6.289999961853027)
Descriptors: MW 459.43, ALogP 1.2, HBA 6, HBD 6, PSA 191.26, QED 0.26
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell Assay: Inhibition of RSK phosphorylation (pRSK with 40%  human serum)
Measurement: IC50 = 225 nM (pChEMBL 6.650000095367432)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): CC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O
InChIKey: LZEMTIAYLKCDHP-GWMMUDDPSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Full agonist activity at mouse MC5R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 756.6, ALogP -0.02, HBA 7, HBD 6, PSA 222.47, QED 0.12
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: LPATVOINCAVXRL-NTBYCYSFSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse melanocortin receptor 5 expressed in HEK293 cells assessed as stimulation of cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 1005.19
Compound (SMILES): O=P(O)(O)Oc1cc(OP(=O)(O)O)c(OP(=O)(O)O)cc1OP(=O)(O)O
InChIKey: OFSQKFMVBPORNX-UHFFFAOYSA-N
Target: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q6P549
Assay: Inhibition of SHIP2 in serum-starved mouse Mm1 cells assessed as reduction in Akt phosphorylation incubated for 30 mins by Western blot analysis
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 462.03, ALogP -0.43, HBA 8, HBD 8, PSA 267.04, QED 0.23
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NC2CCCCC2)c([S+]([O-])Cc2ccccc2)cc1Cl
InChIKey: JLKREKAPCORGQO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 455, ALogP 3.36, HBA 4, HBD 2, PSA 112.32, QED 0.65
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](C)c1cccc(Cc2ccccc2)c1.O=C(O)C(F)(F)F
InChIKey: QXCKSQSCFNLQCL-UFABNHQSSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa-type opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 1 hr by liquid scintillation counting method
Measurement: EC50 > 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 402.54, ALogP 4.35, HBA 3, HBD 3, PSA 75.35, QED 0.55
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of full length human recombinant HDAC7 using Ac-LGK(TFA)-AMC fluorogenic peptide as substrate incubated for 2 hrs by microplate reader assay
Measurement: IC50 = 4550 nM (pChEMBL 5.340000152587891)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): Oc1ccc(/C=N/c2c3c(nc4ccccc24)CCCC3)cc1O
InChIKey: PQHHHZGJZDSJDP-CIAFOILYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChe by Ellman's method
Measurement: IC50 = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 318.38, ALogP 4.28, HBA 4, HBD 2, PSA 65.71, QED 0.55
Compound (SMILES): COc1cc(N2CCCNC2=O)ccc1Nc1ncc(Cl)c(Nc2ccccc2NC(C)=O)n1
InChIKey: KUFBKQQDUMDVPE-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK (1058 to 1620 residues) cytoplasmic domain G1202R mutant using srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 481.94, ALogP 4.5, HBA 7, HBD 4, PSA 120.51, QED 0.39
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3ccc(S(=O)(=O)N4CCN(c5ccc(Cl)cc5)CC4)cc3)nc2n(C)c1=O
InChIKey: HNMAAFCTPZTDQJ-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60612
Assay: Displacement of [3H]CCPA from recombinant mouse A1 adenosine receptor expressed in CHO cell membranes measured after 90 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 1520 nM (pChEMBL 5.820000171661377)
Descriptors: MW 543.05, ALogP 2.66, HBA 8, HBD 1, PSA 113.3, QED 0.4
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCOCCOCCNC(=O)CCCCCN1/C(=C/C=C/C=C/C2=[N+](CCCCS(=O)(=O)[O-])c3ccccc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: BQDLAHRGAQPPJE-WJSZPSLZSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Binding affinity to human neurotensin receptor 1 stably expressed in CHO cells incubated for 75 mins in presence of NT (8 to 13) followed by compound washout with HBSS-BSA by Hoechst H33342 staining based confocal microscopy analysis
Measurement: Kd = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 1658.07
Compound (SMILES): O=C(Cc1ccccc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: YEBWNEBTTYUFMD-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 401.51, ALogP 3.69, HBA 4, HBD 1, PSA 58.36, QED 0.71
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4cc(F)ccc42)CSCC3)cc1
InChIKey: LOFPHNPTVBYXBB-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human HDAC7 using fluorogenic HDAC substrate
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 356.42, ALogP 3.74, HBA 4, HBD 2, PSA 54.26, QED 0.56
Compound (SMILES): CC(C)(C)Cc1cc(-c2onc([C@@H](CCC(=O)[O-])CC(=O)Nc3ccc(Cl)cc3Cl)c2C2CC2)no1.[Na+]
InChIKey: YEQSGBJZMBCONP-RSAXXLAASA-M
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Time-dependent inhibition of human CYP3A4 using testosterone as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 534.44, ALogP 7.08, HBA 6, HBD 2, PSA 118.46, QED 0.29
Compound (SMILES): CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: NJAYXMBERKCZQC-DHXVBOOMSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant human 5HT2A receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 179.24, ALogP 2.09, HBA 1, HBD 1, PSA 12.03, QED 0.75
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2cccc(Br)c2)n(C)c1=O
InChIKey: GDXNESQVHGSDFC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured over 45 mins by horseradish peroxidase-Amplex Red-coupled fluorometric assay
Measurement: IC50 = 396 nM (pChEMBL 6.400000095367432)
Descriptors: MW 404.27, ALogP 1.61, HBA 7, HBD 0, PSA 65.06, QED 0.65
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Ribosomal protein S6 kinase alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK32
Assay: Inhibition of recombinant full length human His6-tagged RSK4 expressed in baculovirus infected sf21 cells using biotin labelled Ahx-KKLNRTLSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1C(N)=O
InChIKey: FFYLSLMDLCQSRS-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2/JAK1 in IFNalpha-stimulated human Kit225 cells by steady-glo luciferase assay
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 380.38, ALogP 2.56, HBA 6, HBD 4, PSA 122.03, QED 0.52