lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnn(-c2cncc(C(F)(F)F)n2)c1
InChIKey: JWIDABJXMBXRBJ-OAHLLOKOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 436.37, ALogP 2.73, HBA 7, HBD 2, PSA 93.96, QED 0.61
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(Cl)c1)c1cnn(-c2cncc(C(F)(F)F)n2)c1
InChIKey: CTQVVHSCIIODID-OAHLLOKOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 452.82, ALogP 3.25, HBA 7, HBD 2, PSA 93.96, QED 0.63
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnn(-c2cc(C(F)(F)F)ncn2)c1
InChIKey: IEJAPGJVISBEIO-OAHLLOKOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 436.37, ALogP 2.73, HBA 7, HBD 2, PSA 93.96, QED 0.61
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnn(-c2ccc(C(F)(F)F)nc2)c1
InChIKey: JRNWUZSLVCHRSS-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 435.38, ALogP 3.34, HBA 6, HBD 2, PSA 81.07, QED 0.61
Compound (SMILES): N#Cc1cnc(-n2cc(C(=O)Nc3ccc([C@H]4CNCCO4)c(F)c3)cn2)cn1
InChIKey: FARGHFZJUXXRLD-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 393.38, ALogP 1.59, HBA 8, HBD 2, PSA 117.75, QED 0.69
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnn(-c2ccnc(C(F)(F)F)n2)c1
InChIKey: TXZHQSVRDDWWRW-OAHLLOKOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 436.37, ALogP 2.73, HBA 7, HBD 2, PSA 93.96, QED 0.61
Compound (SMILES): N#Cc1cc(Cl)cc(C(=O)Nc2ccc([C@H]3CNCCO3)c(F)c2)n1
InChIKey: ZQFFPJVDZSDCAH-MRXNPFEDSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 360.78, ALogP 2.66, HBA 5, HBD 2, PSA 87.04, QED 0.88
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnn(-c2cnc(C(F)(F)F)cn2)c1
InChIKey: ZRTMLVNRXVGSKZ-OAHLLOKOSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 436.37, ALogP 2.73, HBA 7, HBD 2, PSA 93.96, QED 0.61
Compound (SMILES): Cc1nc(C(=O)Nc2ccc([C@H]3CNCCO3)cc2F)ccc1C#N
InChIKey: SBASBXAJQPUXDZ-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 578.3 nM (pChEMBL 6.239999771118164)
Descriptors: MW 340.36, ALogP 2.31, HBA 5, HBD 2, PSA 87.04, QED 0.9
Compound (SMILES): Cc1nc(C(=O)Nc2ccc([C@H]3CNCCO3)c(F)c2)ccc1C#N
InChIKey: IOLQKVXFTBCMAU-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 58.5 nM (pChEMBL 7.230000019073486)
Descriptors: MW 340.36, ALogP 2.31, HBA 5, HBD 2, PSA 87.04, QED 0.9
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)c(F)c1)c1cnc(C(F)(F)F)cn1
InChIKey: FYMXDLNBFVTLCY-CYBMUJFWSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 30.1 nM (pChEMBL 7.519999980926514)
Descriptors: MW 370.31, ALogP 2.55, HBA 5, HBD 2, PSA 76.14, QED 0.81
Compound (SMILES): CCOc1ccc(C(=O)Nc2ccc([C@H]3CNCCO3)cc2F)cn1
InChIKey: WFWLQBHKCLCDNC-MRXNPFEDSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 308.2 nM (pChEMBL 6.510000228881836)
Descriptors: MW 345.37, ALogP 2.53, HBA 5, HBD 2, PSA 72.48, QED 0.87
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc([C@H]3CNCCO3)cc2Cl)c1
InChIKey: ZKAZLEUHOVSETO-QGZVFWFLSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 356.81, ALogP 3.52, HBA 4, HBD 3, PSA 86.18, QED 0.78
Compound (SMILES): O=C(Nc1ccc(Cl)nc1)Nc1ccc([C@H]2CNCCO2)cc1Cl
InChIKey: NZIHRHXPOSUOMI-CQSZACIVSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37 C and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56 C), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/ EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4 C, frozen and stored at -80 C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000 x g for 30 min at 4 C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA.
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 367.24, ALogP 3.69, HBA 4, HBD 3, PSA 75.28, QED 0.72
Compound (SMILES): O=C([C@H]1CC1c1ccccc1)N1CCN(C2CCC2)CC1
InChIKey: GZEMSLIEGKLMPR-DJNXLDHESA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 3.49 nM (pChEMBL 8.460000038146973)
Descriptors: MW 284.4, ALogP 2.49, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): CCCN1CCN(C(=O)[C@H]2CC2c2ccccc2)CC1
InChIKey: NUSUJTLWNODXRI-LYKKTTPLSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 39.68 nM (pChEMBL 7.400000095367432)
Descriptors: MW 272.39, ALogP 2.34, HBA 2, HBD 0, PSA 23.55, QED 0.84
Compound (SMILES): CC(C)N1CCN(C(=O)[C@H]2CC2c2ccc(F)cc2)CC1
InChIKey: UXUFOKSCQDHIIA-LYKKTTPLSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 1.63 nM (pChEMBL 8.789999961853027)
Descriptors: MW 290.38, ALogP 2.48, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): O=C([C@H]1CC1c1ccc(Br)cc1)N1CCN(C2CCC2)CC1
InChIKey: QXNSPQZOLIPIJZ-DJNXLDHESA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 16.8 nM (pChEMBL 7.78000020980835)
Descriptors: MW 363.3, ALogP 3.25, HBA 2, HBD 0, PSA 23.55, QED 0.82
Compound (SMILES): O=C([C@@H]1CC1c1ccc(Br)cc1)N1CCN(C2CCC2)CC1
InChIKey: QXNSPQZOLIPIJZ-ZYMOGRSISA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 363.3, ALogP 3.25, HBA 2, HBD 0, PSA 23.55, QED 0.82
Compound (SMILES): O=C([C@H]1CC1c1ccc(N2CCCC2=O)cc1)N1CCN(C2CCC2)CC1
InChIKey: GTBRJCANRMKUJN-ANYOKISRSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 196.5 nM (pChEMBL 6.710000038146973)
Descriptors: MW 367.49, ALogP 2.61, HBA 3, HBD 0, PSA 43.86, QED 0.82
Compound (SMILES): O=C([C@H]1CC1c1ccc(-c2cn[nH]c2)cc1)N1CCN(C2CCC2)CC1
InChIKey: GCWXDIAMYKKYOJ-ANYOKISRSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 33.92 nM (pChEMBL 7.46999979019165)
Descriptors: MW 350.47, ALogP 2.88, HBA 3, HBD 1, PSA 52.23, QED 0.92
Compound (SMILES): N#Cc1ccc(C2C[C@@H]2C(=O)N2CCN(C3CCC3)CC2)cc1
InChIKey: NXLUQWIKRBZQJH-ZVAWYAOSSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 30.4 nM (pChEMBL 7.519999980926514)
Descriptors: MW 309.41, ALogP 2.36, HBA 3, HBD 0, PSA 47.34, QED 0.86
Compound (SMILES): O=C([C@@H]1CC1c1ccccc1)N1CCN(C2CCC2)CC1
InChIKey: GZEMSLIEGKLMPR-ZYMOGRSISA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 870.4 nM (pChEMBL 6.059999942779541)
Descriptors: MW 284.4, ALogP 2.49, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): CC(C)N1CCN(C(=O)C2CC2c2ccccc2)CC1
InChIKey: FHGXMOHTTKRNRT-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 7010 nM (pChEMBL 5.150000095367432)
Descriptors: MW 272.39, ALogP 2.34, HBA 2, HBD 0, PSA 23.55, QED 0.84
Compound (SMILES): O=C([C@H]1CC1c1cccc(N2CCCC2=O)c1)N1CCN(C2CCC2)CC1
InChIKey: XAGDIZMJFDFBJY-ANYOKISRSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 23.86 nM (pChEMBL 7.619999885559082)
Descriptors: MW 367.49, ALogP 2.61, HBA 3, HBD 0, PSA 43.86, QED 0.82
Compound (SMILES): NC(=O)c1cccc(C2CC2C(=O)N2CCN(C3CCC3)CC2)c1
InChIKey: FKFVDFPNTZKTDS-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 > 1050 nM (pChEMBL 5.979000091552734)
Descriptors: MW 327.43, ALogP 1.59, HBA 3, HBD 1, PSA 66.64, QED 0.91
Compound (SMILES): O=C(C1CC1c1cccc(N2CCCC2=O)c1)N1CCN(C2CCC2)CC1
InChIKey: XAGDIZMJFDFBJY-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 > 1800 nM (pChEMBL 5.744999885559082)
Descriptors: MW 367.49, ALogP 2.61, HBA 3, HBD 0, PSA 43.86, QED 0.82
Compound (SMILES): O=C(C1CC1c1cccc(N2CCCCC2=O)c1)N1CCN(C2CCC2)CC1
InChIKey: GOTOYADHTXKQLS-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 733.4 nM (pChEMBL 6.130000114440918)
Descriptors: MW 381.52, ALogP 3, HBA 3, HBD 0, PSA 43.86, QED 0.81
Compound (SMILES): NC(=O)c1ccc(C2CC2C(=O)N2CCN(C3CCC3)CC2)cc1
InChIKey: VCQZCDSEWSFTPO-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 5.827 nM (pChEMBL 8.229999542236328)
Descriptors: MW 327.43, ALogP 1.59, HBA 3, HBD 1, PSA 66.64, QED 0.91
Compound (SMILES): O=C1N(c2ccnc(Cl)c2)CCN1c1cnccc1C1CC1
InChIKey: QHIQLVPUVUOZHY-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition Assay: Assay method was adopted from a published protocol with some modifications to suit our requirements (Dmitry N Grigoryev et al, Analytical Biochemistry, (1999) 267, 319-330). The conversion of 17-alpha -hydroxy pregnenolone to Dehydroepiandrosterone is accompanied by the release of acetic acid. In the Cyp17 lyase assay, 17-alpha -hydroxy pregnenolone labeled with tritium (3H) at position 21 is used as the substrate. Chloroform extraction removes the radioactive steroids and acetic acid is taken into aqueous layer. The tritiated acetic acid released in the assay thus extracted is quantified to determine the enzyme activity.Initial buffer conditions were, 50 mM Phosphate buffer, pH 7.5 was used as the starting buffer for Cyp17 lyase activity based on the data published in US patent publication No. US2004/0198773 A1. This buffer was found to be suitable for regular Cyp17 lyase assay. Human Cyp 17 gene was cloned and expressed in Adenoviral expression system in A549 cell lines.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 314.78, ALogP 3.45, HBA 3, HBD 0, PSA 49.33, QED 0.82
Compound (SMILES): O=C1N(c2ccnc(C(F)(F)F)c2)CCN1c1cnccc1C1CC1
InChIKey: BKDZEIPQCCUPML-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P11715
Assay: Inhibition Assay: Assay method was adopted from a published protocol with some modifications to suit our requirements (Dmitry N Grigoryev et al, Analytical Biochemistry, (1999) 267, 319-330). The conversion of 17-alpha -hydroxy pregnenolone to Dehydroepiandrosterone is accompanied by the release of acetic acid. In the Cyp17 lyase assay, 17-alpha -hydroxy pregnenolone labeled with tritium (3H) at position 21 is used as the substrate. Chloroform extraction removes the radioactive steroids and acetic acid is taken into aqueous layer. The tritiated acetic acid released in the assay thus extracted is quantified to determine the enzyme activity.Initial buffer conditions were, 50 mM Phosphate buffer, pH 7.5 was used as the starting buffer for Cyp17 lyase activity based on the data published in US patent publication No. US2004/0198773 A1. This buffer was found to be suitable for regular Cyp17 lyase assay. Human Cyp 17 gene was cloned and expressed in Adenoviral expression system in A549 cell lines.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 348.33, ALogP 3.82, HBA 3, HBD 0, PSA 49.33, QED 0.85
Compound (SMILES): COc1cc(N2CCN(c3cnccc3C3CC3)C2=O)ccn1
InChIKey: PNHAORYXCSBTBY-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P11715
Assay: Inhibition Assay: Assay method was adopted from a published protocol with some modifications to suit our requirements (Dmitry N Grigoryev et al, Analytical Biochemistry, (1999) 267, 319-330). The conversion of 17-alpha -hydroxy pregnenolone to Dehydroepiandrosterone is accompanied by the release of acetic acid. In the Cyp17 lyase assay, 17-alpha -hydroxy pregnenolone labeled with tritium (3H) at position 21 is used as the substrate. Chloroform extraction removes the radioactive steroids and acetic acid is taken into aqueous layer. The tritiated acetic acid released in the assay thus extracted is quantified to determine the enzyme activity.Initial buffer conditions were, 50 mM Phosphate buffer, pH 7.5 was used as the starting buffer for Cyp17 lyase activity based on the data published in US patent publication No. US2004/0198773 A1. This buffer was found to be suitable for regular Cyp17 lyase assay. Human Cyp 17 gene was cloned and expressed in Adenoviral expression system in A549 cell lines.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 310.36, ALogP 2.81, HBA 4, HBD 0, PSA 58.56, QED 0.87
Compound (SMILES): O=C1N(c2cnccc2C2CC2)[C@@H]2C[C@@H]2N1c1ccnc(C(F)(F)F)c1
InChIKey: HHSNJLVYXKJDIO-UONOGXRCSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition Assay: Assay method was adopted from a published protocol with some modifications to suit our requirements (Dmitry N Grigoryev et al, Analytical Biochemistry, (1999) 267, 319-330). The conversion of 17-alpha -hydroxy pregnenolone to Dehydroepiandrosterone is accompanied by the release of acetic acid. In the Cyp17 lyase assay, 17-alpha -hydroxy pregnenolone labeled with tritium (3H) at position 21 is used as the substrate. Chloroform extraction removes the radioactive steroids and acetic acid is taken into aqueous layer. The tritiated acetic acid released in the assay thus extracted is quantified to determine the enzyme activity.Initial buffer conditions were, 50 mM Phosphate buffer, pH 7.5 was used as the starting buffer for Cyp17 lyase activity based on the data published in US patent publication No. US2004/0198773 A1. This buffer was found to be suitable for regular Cyp17 lyase assay. Human Cyp 17 gene was cloned and expressed in Adenoviral expression system in A549 cell lines.
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 360.34, ALogP 3.96, HBA 3, HBD 0, PSA 49.33, QED 0.83
Compound (SMILES): O=C(Nc1ccc(Cl)c(C(F)(F)F)c1)N[C@H]1CC[C@H](Oc2ccc(C(F)(F)F)cn2)CC1
InChIKey: ISPSOOYSNVVMMB-MQMHXKEQSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: sEH Assay: See reference (Jones, P. D.; Wolf, N. M.; Morisseau, C.; Whetstone, P.; Hock, B.; Hammock, B. D. Anal. Biochem. 343:66-75; 2005) for sEH assay.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 481.82, ALogP 6.28, HBA 3, HBD 2, PSA 63.25, QED 0.5
Compound (SMILES): CC(C)(C)OC(=O)c1ccc(O[C@H]2CC[C@H](NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)CC2)cn1
InChIKey: AXYKXSDWTCGXGP-KOMQPUFPSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: sEH Assay: See reference (Jones, P. D.; Wolf, N. M.; Morisseau, C.; Whetstone, P.; Hock, B.; Hammock, B. D. Anal. Biochem. 343:66-75; 2005) for sEH assay.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 513.94, ALogP 6.22, HBA 5, HBD 2, PSA 89.55, QED 0.46
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)cc1)N[C@H]1CC[C@H](Oc2ccc(C(=O)O)cc2)CC1
InChIKey: WYKYOQIFUNOEFB-SAABIXHNSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: sEH Assay: See reference (Jones, P. D.; Wolf, N. M.; Morisseau, C.; Whetstone, P.; Hock, B.; Hammock, B. D. Anal. Biochem. 343:66-75; 2005) for sEH assay.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 422.4, ALogP 4.92, HBA 3, HBD 3, PSA 87.66, QED 0.64
Compound (SMILES): N#Cc1ccc(O[C@H]2CC[C@H](NC(=O)Nc3ccc(OC(F)(F)F)cc3)CC2)cc1
InChIKey: AAJZVNIIPZZJJH-RZDIXWSQSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human FAAH expressed in baculovirus-infected High Five cells S9 fraction using OMP substrate by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 419.4, ALogP 4.97, HBA 4, HBD 2, PSA 83.38, QED 0.72
Compound (SMILES): CC(C)[C@H](NC(=O)C(Cc1ccc2ccccc2n1)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(=O)(=O)c1ccccc1)CC(=O)O
InChIKey: CPFXCSLAAJOPLW-SDRXBJFUSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 801.88, ALogP 3.12, HBA 10, HBD 6, PSA 247.26, QED 0.08
Compound (SMILES): CC(C)[C@H](NC(=O)C(Cc1ccc2ccccc2n1)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(C)(=O)=O)CC(=O)O
InChIKey: XDTNISVZIRJASF-DUQXNPHYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 739.8, ALogP 1.69, HBA 10, HBD 6, PSA 247.26, QED 0.11
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)OCc1ccccc1)C(=O)N[C@H](/C=C/S(C)(=O)=O)CC(=O)O
InChIKey: HIQKYBKHPZKDSE-LJKYIEEGSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Fluorometric Enzymatic Assay: Selectivity of compound 55, compound 63, compound 48, compound 57, compound 88 toward caspase-1 (pro-inflammatory group), caspase-5 (group I), caspase-9 (group II) and caspase-3 and caspase-7 (group III) was evaluated by using fluorometric methods using the Caspase-1, -3, -5, -7, -9 Inhibitor Drug Screening Kit (Catalog #: K151-100, K153-100, K155-100/K157-100, K159-100 respectively, BioVision). Briefly, using instructions of the manufacturer, a wide range of different concentrations of the compound: 3333, 1000, 333, 100, 33, 10, 3, and 1 nM (final concentration) was added directly to the reaction mixtures containing the substrate and the enzyme in a final volume of 10 ul. After a 30-minute incubation at 37 C., the liberation of AFC was measured as an endpoint assay using the Flexstation3 (Molecular Devices) with an excitation wavelength of 400 nm and an emission wavelength of 505 nm. The level of inhibition of caspase-1, -3, -5, -7, -9 activity was determined by comparison.
Measurement: IC50 > 3330 nM (pChEMBL 5.478000164031982)
Descriptors: MW 704.76, ALogP 0.85, HBA 10, HBD 7, PSA 254.6, QED 0.11