lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=[N+]([O-])OC[C@H]1O[C@@H](n2cnc3c(NC4CCOC4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: QKLWYFLDTCIMJQ-HVMNINKTSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Radioligand Binding Assay: Membranes for radioligand binding experiments are prepared from fresh or frozen cells as described in Klotz et al., Naunyn-Schmiedeberg's Arch. Pharmacol, 357:1-9 (1998). The cell suspension is then homogenized in ice-cold hypotonic buffer (5 mM Tris/HCl, 2 mM EDTA, pH 7.4) and the homogenate is spun for 10 minutes (4° C.) at 1,000 g. The membranes are then sedimented from the supernatant for 30 minutes at 100,000 g and resuspended in 50 mM Tris/HCl buffer pH 7.4 (for A3 adenosine receptors: 50 mM Tris/HCl, 10 mM MgCl2, 1 mM EDTA, pH 8.25), frozen in liquid nitrogen at a protein concentration of 1-3 mg/mL and stored at −80° C. Dissociation constants of unlabeled compounds (Ki-values) are determined in competition experiments in 96-well microplates using the A1 selective agonist 2-chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA, 1 nM) for the characterization of A1 receptor binding. Nonspecific binding is determined in the presence of 100 Î¼M R-PM and 1 mM theophylline, respectively.
Measurement: Ki = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 382.33, ALogP -1.15, HBA 12, HBD 3, PSA 166.92, QED 0.41
Compound (SMILES): O=[N+]([O-])OC[C@H]1O[C@@H](n2cnc3c(NC4CCCCC4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: AVOAVUPMBQZWSP-XNIJJKJLSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Radioligand Binding Assay: Membranes for radioligand binding experiments are prepared from fresh or frozen cells as described in Klotz et al., Naunyn-Schmiedeberg's Arch. Pharmacol, 357:1-9 (1998). The cell suspension is then homogenized in ice-cold hypotonic buffer (5 mM Tris/HCl, 2 mM EDTA, pH 7.4) and the homogenate is spun for 10 minutes (4° C.) at 1,000 g. The membranes are then sedimented from the supernatant for 30 minutes at 100,000 g and resuspended in 50 mM Tris/HCl buffer pH 7.4 (for A3 adenosine receptors: 50 mM Tris/HCl, 10 mM MgCl2, 1 mM EDTA, pH 8.25), frozen in liquid nitrogen at a protein concentration of 1-3 mg/mL and stored at −80° C. Dissociation constants of unlabeled compounds (Ki-values) are determined in competition experiments in 96-well microplates using the A1 selective agonist 2-chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA, 1 nM) for the characterization of A1 receptor binding. Nonspecific binding is determined in the presence of 100 Î¼M R-PM and 1 mM theophylline, respectively.
Measurement: Ki = 1.32 nM (pChEMBL 8.880000114440918)
Descriptors: MW 394.39, ALogP 0.4, HBA 11, HBD 3, PSA 157.69, QED 0.46
Compound (SMILES): O=[N+]([O-])OC[C@H]1O[C@@H](n2cnc3c(NC4CC5CCC4C5)ncnc32)[C@H](O)[C@@H]1O
InChIKey: QUSKOVZYBDIPDX-STHLEMNDSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Radioligand Binding Assay: Membranes for radioligand binding experiments are prepared from fresh or frozen cells as described in Klotz et al., Naunyn-Schmiedeberg's Arch. Pharmacol, 357:1-9 (1998). The cell suspension is then homogenized in ice-cold hypotonic buffer (5 mM Tris/HCl, 2 mM EDTA, pH 7.4) and the homogenate is spun for 10 minutes (4° C.) at 1,000 g. The membranes are then sedimented from the supernatant for 30 minutes at 100,000 g and resuspended in 50 mM Tris/HCl buffer pH 7.4 (for A3 adenosine receptors: 50 mM Tris/HCl, 10 mM MgCl2, 1 mM EDTA, pH 8.25), frozen in liquid nitrogen at a protein concentration of 1-3 mg/mL and stored at −80° C. Dissociation constants of unlabeled compounds (Ki-values) are determined in competition experiments in 96-well microplates using the A1 selective agonist 2-chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA, 1 nM) for the characterization of A1 receptor binding. Nonspecific binding is determined in the presence of 100 Î¼M R-PM and 1 mM theophylline, respectively.
Measurement: Ki = 1.47 nM (pChEMBL 8.829999923706055)
Descriptors: MW 406.4, ALogP 0.25, HBA 11, HBD 3, PSA 157.69, QED 0.45
Compound (SMILES): O=S(=O)([O-])OC[C@H]1O[C@@H](n2cnc3c(NC4CCCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O.[Na+]
InChIKey: XAPZDPQLAKDNLK-DNBRLMRSSA-M
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Radioligand Binding Assay: Membranes for radioligand binding experiments are prepared from fresh or frozen cells as described in Klotz et al., Naunyn-Schmiedeberg's Arch. Pharmacol, 357:1-9 (1998). The cell suspension is then homogenized in ice-cold hypotonic buffer (5 mM Tris/HCl, 2 mM EDTA, pH 7.4) and the homogenate is spun for 10 minutes (4° C.) at 1,000 g. The membranes are then sedimented from the supernatant for 30 minutes at 100,000 g and resuspended in 50 mM Tris/HCl buffer pH 7.4 (for A3 adenosine receptors: 50 mM Tris/HCl, 10 mM MgCl2, 1 mM EDTA, pH 8.25), frozen in liquid nitrogen at a protein concentration of 1-3 mg/mL and stored at −80° C. Dissociation constants of unlabeled compounds (Ki-values) are determined in competition experiments in 96-well microplates using the A1 selective agonist 2-chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA, 1 nM) for the characterization of A1 receptor binding. Nonspecific binding is determined in the presence of 100 Î¼M R-PM and 1 mM theophylline, respectively.
Measurement: Ki = 1.36 nM (pChEMBL 8.869999885559082)
Descriptors: MW 463.9, ALogP 0.66, HBA 11, HBD 4, PSA 168.92, QED 0.35
Compound (SMILES): O=[N+]([O-])OC[C@H]1O[C@@H](n2cnc3c(NC4CCCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O
InChIKey: CBCZEDFNEMPVHY-SDBHATRESA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Radioligand Binding Assay: Membranes for radioligand binding experiments are prepared from fresh or frozen cells as described in Klotz et al., Naunyn-Schmiedeberg's Arch. Pharmacol, 357:1-9 (1998). The cell suspension is then homogenized in ice-cold hypotonic buffer (5 mM Tris/HCl, 2 mM EDTA, pH 7.4) and the homogenate is spun for 10 minutes (4° C.) at 1,000 g. The membranes are then sedimented from the supernatant for 30 minutes at 100,000 g and resuspended in 50 mM Tris/HCl buffer pH 7.4 (for A3 adenosine receptors: 50 mM Tris/HCl, 10 mM MgCl2, 1 mM EDTA, pH 8.25), frozen in liquid nitrogen at a protein concentration of 1-3 mg/mL and stored at −80° C. Dissociation constants of unlabeled compounds (Ki-values) are determined in competition experiments in 96-well microplates using the A1 selective agonist 2-chloro-N6-[3H]cyclopentyladenosine ([3H]CCPA, 1 nM) for the characterization of A1 receptor binding. Nonspecific binding is determined in the presence of 100 Î¼M R-PM and 1 mM theophylline, respectively.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 428.83, ALogP 1.05, HBA 11, HBD 3, PSA 157.69, QED 0.34
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(Br)cc3)C(c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: VVRNZKKUOWFMOX-NRWPOFLRSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 595.37, ALogP 5.47, HBA 3, HBD 0, PSA 60.93, QED 0.47
Compound (SMILES): COc1ccc(C(=O)N(C)[C@@H]2CCN(C(=O)C3CCN(C(C)=O)CC3)CC2c2ccc(Cl)c(Cl)c2)cc1
InChIKey: OAVNGCZBHRXUGH-ANWICMFUSA-N
Target: Tachykinin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHF0
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 546.5, ALogP 4.72, HBA 4, HBD 0, PSA 70.16, QED 0.54
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(C)cc3)C(c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: FYSFILDCEYJVBF-ANWICMFUSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 530.5, ALogP 5.02, HBA 3, HBD 0, PSA 60.93, QED 0.56
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(Cl)cc3)C(c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: RPTJPWCOBZLMMD-NRWPOFLRSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 550.91, ALogP 5.36, HBA 3, HBD 0, PSA 60.93, QED 0.51
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(-c4ccccc4)cc3)C(c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: KMXLXHFSSQDIGC-VPTMLEGASA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 592.57, ALogP 6.38, HBA 3, HBD 0, PSA 60.93, QED 0.35
Compound (SMILES): CC(=O)C1CCC(C(=O)N2CC(c3ccc(Cl)c(Cl)c3)[C@H](N(C)C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)C2)CC1
InChIKey: CCRJBODRXVWELY-TYHVNVTKSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 637.45, ALogP 7.49, HBA 3, HBD 0, PSA 57.69, QED 0.32
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: PLMUPHYPECRQJW-WIOPSUGQSA-N
Target: Tachykinin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHF0
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 652.46, ALogP 6.75, HBA 3, HBD 0, PSA 60.93, QED 0.34
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(Cl)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: RPTJPWCOBZLMMD-WIOPSUGQSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 550.91, ALogP 5.36, HBA 3, HBD 0, PSA 60.93, QED 0.51
Compound (SMILES): COc1ccc(C(=O)N(C)[C@@H]2CCN(C(=O)C3CCN(C(C)=O)CC3)C[C@H]2c2ccc(Cl)c(Cl)c2)cc1
InChIKey: OAVNGCZBHRXUGH-JYFHCDHNSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 546.5, ALogP 4.72, HBA 4, HBD 0, PSA 70.16, QED 0.54
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(C(F)(F)F)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: LQRMREXDSWNGEJ-WIOPSUGQSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 584.47, ALogP 5.73, HBA 3, HBD 0, PSA 60.93, QED 0.46
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(N4CCOCC4)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: HBSNGWZAWTZUKT-LITSAYRRSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.42 nM (pChEMBL 9.380000114440918)
Descriptors: MW 601.58, ALogP 4.55, HBA 5, HBD 0, PSA 73.4, QED 0.5
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(C4CC4)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: UUPZBGPDEPZRNL-LBNVMWSVSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 556.53, ALogP 5.59, HBA 3, HBD 0, PSA 60.93, QED 0.48
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(Br)cn3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: WQUXLRVVRRBKCO-GBXCKJPGSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 596.35, ALogP 4.87, HBA 4, HBD 0, PSA 73.82, QED 0.51
Compound (SMILES): CN(C(=O)c1ccc(Cl)cc1)[C@@H]1CCN(C(=O)C2CCN(C(=O)CO)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1
InChIKey: JCJPMSLGXSUYHY-XUZZJYLKSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 566.91, ALogP 4.33, HBA 4, HBD 1, PSA 81.16, QED 0.58
Compound (SMILES): CC(=O)N1CCC(CN2CC[C@@H](N(C)C(=O)c3ccc(Cl)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
InChIKey: YGWRUECJIONJNP-JYFHCDHNSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 536.93, ALogP 5.84, HBA 3, HBD 0, PSA 43.86, QED 0.48
Compound (SMILES): CN(C(=O)c1ccc(N2CCOCC2)cc1)[C@@H]1CCN(C(=O)C2CCN(C(=O)C3(O)CC3)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1
InChIKey: JPCIWXKLOABTOR-LITSAYRRSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 643.61, ALogP 4.05, HBA 6, HBD 1, PSA 93.63, QED 0.51
Compound (SMILES): CN(C(=O)c1ccc(C(F)(F)F)cc1)[C@@H]1CCN(C(=O)C2CCN(C(=O)CO)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1
InChIKey: WYMUYTPWSDFTKB-XUZZJYLKSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25103
Assay: Human NK1 Receptor Binding Assay: IM-9 cells (2×10^5 cells/mL) were cultured for 3 days after inoculation, and centrifuged at 500×g for 10 min to give cell pellets. The obtained pellets were washed with PBS (Phosphate-Buffered saline) (GIBCO), disrupted in buffer A (50 mM Tris-hydrochloric acid buffer (Tris-HCl) (pH 7.4) containing 120 mM sodium chloride, 5 mM potassium chloride, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and 1 mM ethylenediaminetetraacetic acid (EDTA)) using a Polytron homogenizer (Kinematika, Germany), and centrifuged at 100,000×g for 40 min. The precipitation fraction was suspended in buffer B (50 mM Tris-HCl (pH 7.4), 0.02% bovine serum albumin, 2 μg/mL chymostatin, 40 μg/mL bacitracin, 40 μg/mL APMSF, 3 mM manganese dichloride (MnCl2)) and cryopreserved (−80° C.) as a receptor reference standard. Buffer B (50 μL) was added to a 96-well microassay plate (Corning Incorporated). The membrane reference standard suspended in buffer B at 250 μg/mL was added by 50 μL. A measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the total binding, 4 μM non-labeled SP diluted with a measurement buffer containing 2% dimethyl sulfoxide was added by 50 μL to examine the non-specific binding, and a test compound diluted with a measurement buffer (containing 2% dimethyl sulfoxide) was added by 50 μL to examine the binding inhibitory activity of the test compound. Furthermore, 400 μM 125I-Bolton-Hunter-SP (BH-SP) solution was added to each well by 50 μL. After reaction at room temperature for 30 min, the reaction was quenched using a cell harvester (PerkinElmer) by rapid filtration on a GF/C filter plate (PerkinElmer), and the cells were washed 10 times with 250 μL of a 50 mM Tris-hydrochloric acid buffer (pH 7.4) containing 0.02% bovine serum albumin. The GF/C filter plate was dried, MicroScinti-0 (PerkinElmer) was added by 20 μL, and the radioactivity was measured on a TopCount (PerkinElmer). The GF/C filter plate was immersed in 0.3% polyethyleneimine for one day before use.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 600.47, ALogP 4.7, HBA 4, HBD 1, PSA 81.16, QED 0.54