lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccnc(NC(=O)c2cc(F)cc(Oc3cncnc3)c2)n1
InChIKey: GCQMRMPNHPBXIY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 325.3, ALogP 2.76, HBA 6, HBD 1, PSA 89.89, QED 0.79
Compound (SMILES): Cc1nc(NC(=O)c2cc(F)cc(Oc3cncnc3)c2)sc1Br
InChIKey: YRZJRVLGAJFCTI-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.24, ALogP 4.19, HBA 6, HBD 1, PSA 77, QED 0.7
Compound (SMILES): CNc1nc(Nc2cc3oc(=O)n(C)c3cc2Cl)ncc1C(F)(F)F
InChIKey: XAHLCECLVUVWOW-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Lanthascreen Binding Assay: his assay was used to determine a compound's potency in inhibiting activity of LRRK2 by determining, Kiapp, IC50, or percent inhibition values. In 384 well proxiplates F black, shallow well plates LRRK2, Eu-anti-GST-antibody, Alexa Fluor Kinase tracer 236 and test compound were incubated together. Binding of the Alexa Fluor tracer to a kinase was detected by addition of a Eu-labeled anti-GST antibody. Binding of the tracer and antibody to a kinase results in a high degree of FRET, whereas displacement of the tracer with a kinase inhibitor results in a loss of FRET. Assay conditions and materials used were as follows:Final Assay Conditions:GST-LRRK2 G2019S 10 nMEu-anti-GST-antibody 2 nMKinase tracer 236 8.5 nMKinase reaction time: 1 hourTemperature: ambientTotal volume: 15 ulDMSO 1%Materials:384 well proxiplates F black shallow well Perkin Elmer cat#6008260Kinase: LRRK2 G2019S Invitrogen cat #PV4882(LOT 567054A).
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 373.72, ALogP 3.38, HBA 7, HBD 2, PSA 84.98, QED 0.73
Compound (SMILES): CN(C)CCN(C)c1ccnc(N)n1
InChIKey: SGPKVIBSNJZALW-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 257 nM (pChEMBL 6.590000152587891)
Descriptors: MW 195.27, ALogP 0.06, HBA 5, HBD 1, PSA 58.28, QED 0.74
Compound (SMILES): NCCCNc1ccnc(N)n1
InChIKey: OSJDAJBEHUXALX-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 61.7 nM (pChEMBL 7.210000038146973)
Descriptors: MW 167.22, ALogP -0.18, HBA 5, HBD 3, PSA 89.85, QED 0.54
Compound (SMILES): CNCCCNc1ccnc(N)n1
InChIKey: VWXNURUJIXIAMU-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 28.2 nM (pChEMBL 7.550000190734863)
Descriptors: MW 181.24, ALogP 0.08, HBA 5, HBD 3, PSA 75.86, QED 0.56
Compound (SMILES): CN(CCCN)c1ccnc(N)n1
InChIKey: YRFPUFORQQMIOC-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 316 nM (pChEMBL 6.5)
Descriptors: MW 181.24, ALogP -0.16, HBA 5, HBD 2, PSA 81.06, QED 0.67
Compound (SMILES): CCC(N)CCNc1ccnc(N)n1
InChIKey: CPLJBGQJNJXCGU-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 178 nM (pChEMBL 6.75)
Descriptors: MW 195.27, ALogP 0.6, HBA 5, HBD 3, PSA 89.85, QED 0.64
Compound (SMILES): CC(C)(CN)CNc1ccnc(N)n1
InChIKey: INEWUXZQWNFHHQ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 195.27, ALogP 0.46, HBA 5, HBD 3, PSA 89.85, QED 0.65
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(c2ccnc(N)n2)CC1
InChIKey: IQDWTLZCXHUGAQ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 279.34, ALogP 1.12, HBA 6, HBD 1, PSA 84.58, QED 0.83
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(CNc2ccnc(N)n2)CC1
InChIKey: UYOIKAQMLYTPRT-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 331 nM (pChEMBL 6.480000019073486)
Descriptors: MW 307.4, ALogP 2.12, HBA 6, HBD 2, PSA 93.37, QED 0.89
Compound (SMILES): Nc1nccc(NC2CCC(N)CC2)n1
InChIKey: IKGWHSHRVBKXSO-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 207.28, ALogP 0.74, HBA 5, HBD 3, PSA 89.85, QED 0.67
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@@H](Nc2ccnc(N)n2)C1
InChIKey: ANCRHFIYTPCEEZ-SECBINFHSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 279.34, ALogP 1.48, HBA 6, HBD 2, PSA 93.37, QED 0.85
Compound (SMILES): Nc1nccc(N[C@@H]2CCNC2)n1
InChIKey: GHNOFPTUISNCFA-ZCFIWIBFSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 179.23, ALogP -0.17, HBA 5, HBD 3, PSA 75.86, QED 0.59
Compound (SMILES): Nc1nccc(N2C[C@H]3CN(Cc4ccccc4)C[C@H]3C2)n1
InChIKey: CTCFRTYLQWWNHX-GASCZTMLSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 295.39, ALogP 1.63, HBA 5, HBD 1, PSA 58.28, QED 0.93
Compound (SMILES): Nc1nccc(N2CCC(N)CC2)n1
InChIKey: KBZTWADNPXTKQW-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 193.25, ALogP -0.01, HBA 5, HBD 2, PSA 81.06, QED 0.66
Compound (SMILES): Nc1nccc(N2CCCN(Cc3ccccc3)CCC2)n1
InChIKey: FCVGQACZWWDJJA-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 297.41, ALogP 2.16, HBA 5, HBD 1, PSA 58.28, QED 0.94
Compound (SMILES): Nc1nccc(NC2CNC2)n1
InChIKey: XYMKKWFUDJRTSZ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 33.1 nM (pChEMBL 7.480000019073486)
Descriptors: MW 165.2, ALogP -0.56, HBA 5, HBD 3, PSA 75.86, QED 0.55
Compound (SMILES): Nc1nccc(N2CCC3(CC2)CNC3)n1
InChIKey: LUKGRPKULAYZKC-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 219.29, ALogP 0.25, HBA 5, HBD 2, PSA 67.07, QED 0.71
Compound (SMILES): Nc1nccc(NC2CCNCC2)n1
InChIKey: FWDROTDBZOBNLC-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 193.25, ALogP 0.22, HBA 5, HBD 3, PSA 75.86, QED 0.63
Compound (SMILES): Nc1nccc(N2CCNCC2)n1
InChIKey: DWNUPEANFAMUBK-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 5.75 nM (pChEMBL 8.239999771118164)
Descriptors: MW 179.23, ALogP -0.53, HBA 5, HBD 2, PSA 67.07, QED 0.61
Compound (SMILES): CN(C)CCNc1ccnc(N)n1
InChIKey: VJADDTSYMSFSEM-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 181.24, ALogP 0.03, HBA 5, HBD 2, PSA 67.07, QED 0.69
Compound (SMILES): CC(N)CNc1ccnc(N)n1
InChIKey: IAFGECINGVZOBV-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 167.22, ALogP -0.18, HBA 5, HBD 3, PSA 89.85, QED 0.58
Compound (SMILES): CC(C)(N)CNc1ccnc(N)n1
InChIKey: FYQMDSGCGAIEFE-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki > 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 181.24, ALogP 0.21, HBA 5, HBD 3, PSA 89.85, QED 0.62
Compound (SMILES): Nc1nccc(NC2CCN(Cc3ccccc3)CC2)n1
InChIKey: KHDNZZFBIJGVER-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Competition Binding Assay: The rat H3 receptor was cloned and expressed in cells, and competition binding assays carried out, according to methods previously described (see Esbenshade, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 313, 165-175; Esbenshade et al., Biochemical Pharmacology 2004, 68, 933-945; and Krueger, et al. Journal of Pharmacology and Experimental Therapeutics 2005, 314, 271-281). Membranes were prepared from C6 or HEK293 cells, expressing the rat histamine H3 receptor, by homogenization on ice in TE buffer (50 mM Tris-HCl buffer, pH 7.4, containing 5 mM EDTA), 1 mM benzamidine, 2 ug/ml aprotinin, 1 ug/ml leupeptin, and 1 ug/ml pepstatin. The homogenate was centrifuged at 40,000 g for 20 minutes at 4 C. This step was repeated, and the resulting pellet was resuspended in TE buffer. Aliquots were frozen at -70 C. until needed. On the day of assay, membranes were thawed and diluted with TE buffer.
Measurement: Ki = 24.5 nM (pChEMBL 7.610000133514404)
Descriptors: MW 283.38, ALogP 2.14, HBA 5, HBD 2, PSA 67.07, QED 0.9
Compound (SMILES): CC(=O)NC(C)Cc1ccc(C#Cc2cnc(OCc3cccc(F)c3)nc2)cc1
InChIKey: SPFPPXPEYJWHFV-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Malonyl CoA formation by acetyl CoA carboxylases is stoichometrically linked to the consumption of ATP. ACC2 activity is measured in a NADH-linked kinetic method measuring ADP generated during the ACC reaction using a coupled lactate dehydrogenase/pyruvate kinase reaction.For biological testing, a human ACC2 construct which lacks the 128 amino acids at the N-terminus for increased solubility (nt 385-6966 in Genbank entry AJ575592) is cloned. The protein is then expressed in insect cells using a baculoviral expression system. Protein purification is performed by anion exchange.All compounds are dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM.Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/mL BSA, 3.75 mM reduced L-glutathione, 15 U/mL lactate dehydrogenase, 0.5 mM phosphoenolpyruvate.
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 403.46, ALogP 3.66, HBA 4, HBD 1, PSA 64.11, QED 0.64
Compound (SMILES): CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3cn(-c4ccccc4)nn3)n2)cc1
InChIKey: GJAQQKJDEHDCCU-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length ATM (unknown origin) using DPSVEPPLSQETFSDKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 420.5, ALogP 3.16, HBA 8, HBD 1, PSA 116.65, QED 0.53
Compound (SMILES): CC(C)(C)OC(=O)N1CC2CN(c3nc4ccccc4n(C4CCN(C5CCCCCCC5)CC4)c3=O)CC2C1
InChIKey: YPKXYQGFBGHFRA-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 3869 nM (pChEMBL 5.409999847412109)
Descriptors: MW 549.76, ALogP 5.45, HBA 7, HBD 0, PSA 70.91, QED 0.51
Compound (SMILES): O=c1c(NCC(O)CO)nc2ccccc2n1[C@H]1C[C@H]2CC[C@@H](C1)N2C1CCCCCCC1
InChIKey: BKBGBNKHUNQUQH-PZDACTEOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 394.3 nM (pChEMBL 6.400000095367432)
Descriptors: MW 454.62, ALogP 3.44, HBA 7, HBD 3, PSA 90.62, QED 0.62
Compound (SMILES): NC(=O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: LSINLLSZBVYZJF-BWTSREIZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 819 nM (pChEMBL 6.090000152587891)
Descriptors: MW 408.55, ALogP 3.78, HBA 5, HBD 1, PSA 81.22, QED 0.84
Compound (SMILES): O=C(O)C1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)CC1
InChIKey: BIIKQRYVAUBKEY-UBRQYEGLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 1670 nM (pChEMBL 5.78000020980835)
Descriptors: MW 492.66, ALogP 4.98, HBA 6, HBD 1, PSA 78.67, QED 0.65
Compound (SMILES): N[C@@H]1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)C1
InChIKey: SMXDKYPJJWXFLI-LGKPFJOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 449.64, ALogP 4.21, HBA 6, HBD 1, PSA 67.39, QED 0.76
Compound (SMILES): NC(=O)[C@H](CO)Nc1nc2ccccc2n([C@@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: YSTQEMAOTSXQDC-IIZPIQPGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 467.61, ALogP 2.94, HBA 7, HBD 3, PSA 113.48, QED 0.6
Compound (SMILES): O=C(O)CNc1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: OBZVJUBYNSDNFQ-PMOLBWCYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 1172 nM (pChEMBL 5.929999828338623)
Descriptors: MW 438.57, ALogP 4.17, HBA 6, HBD 2, PSA 87.46, QED 0.73
Compound (SMILES): O=C(O)Cc1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: RSYJMTSEPZEHFW-AERCQKQUSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 12825 nM (pChEMBL 4.889999866485596)
Descriptors: MW 437.58, ALogP 4.69, HBA 5, HBD 1, PSA 75.43, QED 0.75
Compound (SMILES): O=C(O)CC1CCN(c2nc3ccccc3n([C@H]3C[C@H]4CC[C@@H](C3)N4C3CCCCCCC3)c2=O)C1
InChIKey: HSXPNGSPJHVJRG-WIXXOLQWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 492.66, ALogP 4.98, HBA 6, HBD 1, PSA 78.67, QED 0.63
Compound (SMILES): O=C(O)[C@@H](CO)Nc1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: UWTSOPBZAAXFLK-FCIYXJNOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 468.6, ALogP 3.53, HBA 7, HBD 3, PSA 107.69, QED 0.6
Compound (SMILES): Cc1cc(C)nc(SCc2ccc(C(=O)NN/C=C3\C=CC=C(O)C3=O)cc2)n1
InChIKey: ICUUJCCUPXXXGD-GZTJUZNOSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1nM [3H]-nociceptin (NEN; 87.7 Cl/nimole) with 10-20 ug membrane protein in a final volume of 500uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. Fifty uL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 836 nM (pChEMBL 6.079999923706055)
Descriptors: MW 408.48, ALogP 3.08, HBA 7, HBD 3, PSA 104.21, QED 0.29
Compound (SMILES): O=C1CCN(c2nc3ccccc3n(C3CCN(C4CCCCCCC4)CC3)c2=O)N1
InChIKey: BFATVKDIMUJHBW-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 3330 nM (pChEMBL 5.480000019073486)
Descriptors: MW 423.56, ALogP 3.39, HBA 6, HBD 1, PSA 70.47, QED 0.82