lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC4)C3)ncc2C(=O)NCc2ccc(F)cc2)cc1Cl
InChIKey: DGSHYRLGEKHHEQ-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Caliper Mobility-Shift Assay: A sample to be tested is precisely weighed, dissolved by adding DMSO, mixed sufficiently to form 10 mM solution. The above mother solution is diluted with DMSO to 0.5 mM, then diluted in 3.162 gradient multiple to obtain total 11 concentrations.20 ul of substrate 10 uM FL-cGMP was added to 96-well plate, to which was added 1 ul of compound DMSO solution or compound-free DMSO solution, then was added 29 ul of 1.38 ng/ul PDE-5A enzyme buffer solution (100 mM Hepes pH 7.5, 5 mM MgCl2, 0.002% Brij-35). The maximum final concentration of the compound was 10 uM. After incubation at 30 C. for 1 h, 20 ul of 70 uM EDTA was added to terminate reaction. Substrate and products were separated and analyzed by electrophoresis.
Measurement: IC50 = 2.077 nM (pChEMBL 8.680000305175781)
Descriptors: MW 496.97, ALogP 4.78, HBA 6, HBD 1, PSA 76.58, QED 0.48
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC4)C3)ncc2C(=O)NCc2ncccn2)cc1Cl
InChIKey: WWGBQFNTESBLDK-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Caliper Mobility-Shift Assay: A sample to be tested is precisely weighed, dissolved by adding DMSO, mixed sufficiently to form 10 mM solution. The above mother solution is diluted with DMSO to 0.5 mM, then diluted in 3.162 gradient multiple to obtain total 11 concentrations.20 ul of substrate 10 uM FL-cGMP was added to 96-well plate, to which was added 1 ul of compound DMSO solution or compound-free DMSO solution, then was added 29 ul of 1.38 ng/ul PDE-5A enzyme buffer solution (100 mM Hepes pH 7.5, 5 mM MgCl2, 0.002% Brij-35). The maximum final concentration of the compound was 10 uM. After incubation at 30 C. for 1 h, 20 ul of 70 uM EDTA was added to terminate reaction. Substrate and products were separated and analyzed by electrophoresis.
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 480.96, ALogP 3.43, HBA 8, HBD 1, PSA 102.36, QED 0.52
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC4)C3)ncc2C(=O)N[C@H]2CC[C@H](O)CC2)cc1Cl
InChIKey: WXEZZMYEXDEVQT-IYARVYRRSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Caliper Mobility-Shift Assay: A sample to be tested is precisely weighed, dissolved by adding DMSO, mixed sufficiently to form 10 mM solution. The above mother solution is diluted with DMSO to 0.5 mM, then diluted in 3.162 gradient multiple to obtain total 11 concentrations.20 ul of substrate 10 uM FL-cGMP was added to 96-well plate, to which was added 1 ul of compound DMSO solution or compound-free DMSO solution, then was added 29 ul of 1.38 ng/ul PDE-5A enzyme buffer solution (100 mM Hepes pH 7.5, 5 mM MgCl2, 0.002% Brij-35). The maximum final concentration of the compound was 10 uM. After incubation at 30 C. for 1 h, 20 ul of 70 uM EDTA was added to terminate reaction. Substrate and products were separated and analyzed by electrophoresis.
Measurement: IC50 = 4.079 nM (pChEMBL 8.390000343322754)
Descriptors: MW 487, ALogP 3.74, HBA 7, HBD 2, PSA 96.81, QED 0.61
Compound (SMILES): O=C(Cc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2c1OCC1(COC1)CO2
InChIKey: JKFYCZMQKAASOL-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 446.23, ALogP 4.2, HBA 6, HBD 0, PSA 66.88, QED 0.64
Compound (SMILES): O=C(Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c2c1OCC1(COC1)CO2
InChIKey: CYUPKOBVTTXVDW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 462.23, ALogP 3.44, HBA 6, HBD 0, PSA 80.93, QED 0.38
Compound (SMILES): O=C(Cc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2c1OCC1(CCOCC1)CO2
InChIKey: UXBXTVKJSUFNGD-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 474.29, ALogP 4.98, HBA 6, HBD 0, PSA 66.88, QED 0.57
Compound (SMILES): O=C(Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c2c1OCC1(CCOCC1)CO2
InChIKey: KJEJDSUPYMGLSF-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 490.29, ALogP 4.22, HBA 6, HBD 0, PSA 80.93, QED 0.35
Compound (SMILES): O=C(Cc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2c1OC1(CCOCC1)O2
InChIKey: SKJBPWNKKILJEX-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 446.23, ALogP 4.69, HBA 6, HBD 0, PSA 66.88, QED 0.62
Compound (SMILES): O=C(Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c2c1OC1(CCOCC1)O2
InChIKey: OKFVVVLMOSICEZ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 462.23, ALogP 3.93, HBA 6, HBD 0, PSA 80.93, QED 0.38
Compound (SMILES): O=C(Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c2c1OC1(CCS(=O)(=O)CC1)O2
InChIKey: ZININGNRPUGNSL-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 510.3, ALogP 3.33, HBA 7, HBD 0, PSA 105.84, QED 0.35
Compound (SMILES): O=C(Cc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2c1OC1(CCS(=O)(=O)CC1)O2
InChIKey: VXTGXSDITDITKB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 494.3, ALogP 4.09, HBA 7, HBD 0, PSA 91.79, QED 0.58
Compound (SMILES): O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2c1OC1(CCSCC1)O2
InChIKey: LXHMXTSEVTVMHJ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 463.29, ALogP 5.24, HBA 6, HBD 1, PSA 69.68, QED 0.67
Compound (SMILES): O=C(Nc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c2c1OC1(CCS(=O)(=O)CC1)O2
InChIKey: XMIOVXNHWDNUGJ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Human recombinant PDE4 (Genbank accession no NM006203) was incubated for 1 hour, with the test compound at concentrations up to 10 μM, with cAMP (1x10-5M) , and with a low amount (0.021 MBq) of radioactively labelled cAMP. At the end of the incubation, the cleavage of the substrate was evaluated by the binding of the AMP product to SPA beads, which generate chemoluminescence when bound to the radioactive tracer. The AMP product inhibited the binding of the radioactive tracer to the beads, and the luminescent signal was competed.
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 511.29, ALogP 3.16, HBA 7, HBD 1, PSA 117.87, QED 0.5
Compound (SMILES): Nc1noc2cc(NC(=O)C(O)c3cccn(-c4ccc(OC(F)(F)F)cc4)c3=O)ccc12
InChIKey: LMDYTZLOSRFUFL-UHFFFAOYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition Assay: Inhibitory activity against Factor IXa was tested using the substrate SPECTROFLUOR FIXa (American Diagnostica Inc.; 500 West Avenue, Stamford, Conn. 06902 USA; Pr. No. 299F) and human Factor IXa (American Diagnostica Inc.; Pr. No. 449b). Test substances dissolved in buffer A (50 mM α,α,α-tris(hydroxymethyl)methylamine (Tris), 100 mM NaCl, 5 mM CaCl2, 15% (v/v) ethylene glycol, pH 8.0) were mixed with Factor IXa (2.0 μg/ml final concentration). The enzyme reaction was started by addition of SPECTROFLUOR FIXa (100 μM final concentration). After incubation for 60 minutes at room temperature, the reaction was stopped by the addition of 20% (v/v) acetic acid solution, and then fluorescence value measured (Excitation Wavelength: 355 nm, Emission Wavelength; 460 nm) in a microtiter plate reader (ARVO 1420 Multilabel Counter; PerkinElmer).
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 460.37, ALogP 3.13, HBA 8, HBD 3, PSA 132.61, QED 0.42
Compound (SMILES): CC(C)(C)c1ccc(-n2cccc(C(O)C(=O)Nc3ccc4c(N)nccc4c3)c2=O)cc1
InChIKey: YRFVZBOJIOTDGE-UHFFFAOYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition Assay: Inhibitory activity against Factor IXa was tested using the substrate SPECTROFLUOR FIXa (American Diagnostica Inc.; 500 West Avenue, Stamford, Conn. 06902 USA; Pr. No. 299F) and human Factor IXa (American Diagnostica Inc.; Pr. No. 449b). Test substances dissolved in buffer A (50 mM α,α,α-tris(hydroxymethyl)methylamine (Tris), 100 mM NaCl, 5 mM CaCl2, 15% (v/v) ethylene glycol, pH 8.0) were mixed with Factor IXa (2.0 μg/ml final concentration). The enzyme reaction was started by addition of SPECTROFLUOR FIXa (100 μM final concentration). After incubation for 60 minutes at room temperature, the reaction was stopped by the addition of 20% (v/v) acetic acid solution, and then fluorescence value measured (Excitation Wavelength: 355 nm, Emission Wavelength; 460 nm) in a microtiter plate reader (ARVO 1420 Multilabel Counter; PerkinElmer).
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 442.52, ALogP 3.94, HBA 6, HBD 3, PSA 110.24, QED 0.44
Compound (SMILES): CC(C)(C)c1ccc(-n2cccc(C(O)C(=O)Nc3ccc4c(N)noc4c3)c2=O)cc1
InChIKey: JUQNBYNLXVRFQQ-UHFFFAOYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition Assay: Inhibitory activity against Factor IXa was tested using the substrate SPECTROFLUOR FIXa (American Diagnostica Inc.; 500 West Avenue, Stamford, Conn. 06902 USA; Pr. No. 299F) and human Factor IXa (American Diagnostica Inc.; Pr. No. 449b). Test substances dissolved in buffer A (50 mM α,α,α-tris(hydroxymethyl)methylamine (Tris), 100 mM NaCl, 5 mM CaCl2, 15% (v/v) ethylene glycol, pH 8.0) were mixed with Factor IXa (2.0 μg/ml final concentration). The enzyme reaction was started by addition of SPECTROFLUOR FIXa (100 μM final concentration). After incubation for 60 minutes at room temperature, the reaction was stopped by the addition of 20% (v/v) acetic acid solution, and then fluorescence value measured (Excitation Wavelength: 355 nm, Emission Wavelength; 460 nm) in a microtiter plate reader (ARVO 1420 Multilabel Counter; PerkinElmer).
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 432.48, ALogP 3.53, HBA 7, HBD 3, PSA 123.38, QED 0.45
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@H]1CCO[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: YZSVWRPXYBVLMX-QANKJYHBSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 412.46, ALogP 1.53, HBA 7, HBD 1, PSA 90.45, QED 0.82
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnn(-c4ncccn4)c3C2)CCO[C@@H]1c1cc(F)ccc1F
InChIKey: IKCBUWKIWWSWRR-ZAAXVRCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 412.44, ALogP 2.5, HBA 7, HBD 1, PSA 82.09, QED 0.71
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnn(-c4ccccc4)c3C2)CCO[C@@H]1c1cc(F)ccc1F
InChIKey: HYYNKMBJAHIQSY-AVCGJXAMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 410.47, ALogP 3.71, HBA 5, HBD 1, PSA 56.31, QED 0.72
Compound (SMILES): N#Cc1n[nH]c2c1CN([C@H]1CCO[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: OJBFOFZZJREKGO-GEWABHDNSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 359.38, ALogP 2.12, HBA 5, HBD 2, PSA 90.96, QED 0.86
Compound (SMILES): NC(=O)c1n[nH]c2c1CN([C@H]1CCO[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: PLSSYCJFUXCTAF-RMLVOYDJSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 377.4, ALogP 1.35, HBA 5, HBD 3, PSA 110.26, QED 0.75
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cn(S(=O)(=O)C4CC4)nc3C2)CCO[C@@H]1c1cc(F)ccc1F
InChIKey: HAXLNGXZFWYLRF-ADLFWFRXSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 438.5, ALogP 2.06, HBA 7, HBD 1, PSA 90.45, QED 0.79
Compound (SMILES): Cc1c2c(nn1S(=O)(=O)C1(C)CC1)CN([C@H]1CCO[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: CBZBBEYWAOHFSD-PAXLWEDBSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 466.55, ALogP 2.76, HBA 7, HBD 1, PSA 90.45, QED 0.75
Compound (SMILES): CC1(S(=O)(=O)n2cc3c(n2)CN([C@H]2CCO[C@H](c4cc(F)c(F)cc4F)[C@@H](N)C2)C3)CC1
InChIKey: TWFBZRZOOKTCAT-YHJVDBJQSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 470.52, ALogP 2.59, HBA 7, HBD 1, PSA 90.45, QED 0.69
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnc(C4CC4)nc3C2)CCO[C@@H]1c1cc(F)ccc1F
InChIKey: GYPVRZYIESKIEZ-ZAAXVRCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 386.45, ALogP 3.2, HBA 5, HBD 1, PSA 64.27, QED 0.88
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@H]1CCS[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: PDTMGCHVHVHPJV-QANKJYHBSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 14.3 nM (pChEMBL 7.840000152587891)
Descriptors: MW 428.53, ALogP 2.25, HBA 7, HBD 1, PSA 81.22, QED 0.81
Compound (SMILES): CC(C)(O)Cn1cc2c(n1)CN([C@H]1CCO[C@H](c3cc(F)ccc3F)[C@@H](N)C1)C2
InChIKey: BJOUYUPISJUJNM-ZAAXVRCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 21.1 nM (pChEMBL 7.679999828338623)
Descriptors: MW 406.48, ALogP 2.5, HBA 6, HBD 2, PSA 76.54, QED 0.82
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnn(-c4ccc(C(F)(F)F)cn4)c3C2)CCO[C@@H]1c1cc(F)ccc1F
InChIKey: XNZHWENQBRYHDU-XWFZLUIHSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 479.45, ALogP 4.13, HBA 6, HBD 1, PSA 69.2, QED 0.57
Compound (SMILES): CC1(S(=O)(=O)n2cc3c(n2)CN([C@H]2CCO[C@H](c4cc(F)ccc4F)[C@@H](N)C2)C3)CC1
InChIKey: OYGXGJMMFOYYGA-ZAAXVRCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Fluorometric Assay: A continuous fluorometric assay is employed with the substrate Gly-Pro-AMC, which is cleaved by DPP-4 to release the fluorescent AMC leaving group. The kinetic parameters that describe this reaction are as follows: Km=50 uM; kcat=75 s-1; kcat/Km=1.5x106 M-1s-1. A typical reaction contains approximately 50 pM enzyme, 50 uM Gly-Pro-AMC, and buffer (100 mM HEPES, pH 7.5, 0.1 mg/ml BSA) in a total reaction volume of 100 uL. Liberation of AMC is monitored continuously in a 96-well plate fluorometer using an excitation wavelength of 360 nm and an emission wavelength of 460 nm. Under these conditions, approximately 0.8 uM AMC is produced in 30 minutes at 25 degrees C. The enzyme used in these studies was soluble (transmembrane domain and cytoplasmic extension excluded) human protein produced in a baculovirus expression system (Bac-To-Bac, Gibco BRL). The kinetic constants for hydrolysis of Gly-Pro-AMC and GLP-1 were found to be in accord with literature.
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 452.53, ALogP 2.45, HBA 7, HBD 1, PSA 90.45, QED 0.77
Compound (SMILES): Cc1ncc([N+](=O)[O-])n1CCOS(=O)(=O)ON
InChIKey: YZWMPVHXWBGMRV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition Assay: The inhibition constants (K) the compounds for four CA isozymes, CA I, II, IX and XII were determined. An Applied Photophysics (Oxford, UK) stopped-flow instrument has been used for assaying the CA-catalyzed CO2 hydration activity (Khalifah, 1971). Phenol red (at a concentration of 0.2 mM) has been used as indicator, working at the absorbance maximum of 557 nm, with 10 mM Hepes (pH 7.5) as buffer, 0.1 M Na2SO (for maintaining constant the ionic strength), following the CA-catalyzed CO2 hydration reaction for a period of 10-100 s. The CO2 concentrations ranged from 1.7 to 17 mM for the determination of the kinetic parameters and inhibition constants. For each inhibitor at least six traces of the initial 5-10% of the reaction have been used for determining the initial velocity. The uncatalyzed rates were determined in the same manner and subtracted from the total observed rates. Stock solutions of inhibitor (1 mM) were prepared in distilled-deionized water with 10-20% (v/v) DMSO.
Measurement: Ki = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 266.24, ALogP -0.75, HBA 9, HBD 1, PSA 139.58, QED 0.52
Compound (SMILES): Cc1ncc([N+](=O)[O-])n1CCNS(=O)(=O)ON
InChIKey: YGMPOBRDSLWGFP-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition Assay: The inhibition constants (K) the compounds for four CA isozymes, CA I, II, IX and XII were determined. An Applied Photophysics (Oxford, UK) stopped-flow instrument has been used for assaying the CA-catalyzed CO2 hydration activity (Khalifah, 1971). Phenol red (at a concentration of 0.2 mM) has been used as indicator, working at the absorbance maximum of 557 nm, with 10 mM Hepes (pH 7.5) as buffer, 0.1 M Na2SO (for maintaining constant the ionic strength), following the CA-catalyzed CO2 hydration reaction for a period of 10-100 s. The CO2 concentrations ranged from 1.7 to 17 mM for the determination of the kinetic parameters and inhibition constants. For each inhibitor at least six traces of the initial 5-10% of the reaction have been used for determining the initial velocity. The uncatalyzed rates were determined in the same manner and subtracted from the total observed rates. Stock solutions of inhibitor (1 mM) were prepared in distilled-deionized water with 10-20% (v/v) DMSO.
Measurement: Ki = 9576 nM (pChEMBL 5.019999980926514)
Descriptors: MW 265.25, ALogP -1.18, HBA 8, HBD 2, PSA 142.38, QED 0.49
Compound (SMILES): CC(C)(NC(=O)c1ccc2c(c1OCCC1CCCCC1)CCCC2)C(=O)O
InChIKey: RVQOKKHTGALHFH-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 387.52, ALogP 4.51, HBA 3, HBD 2, PSA 75.63, QED 0.72
Compound (SMILES): CC(C)(NC(=O)c1ccc2c(c1OCCOc1ccccc1)CCCC2)C(=O)O
InChIKey: NJOHIVWMBOEAHQ-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 397.47, ALogP 3.62, HBA 4, HBD 2, PSA 84.86, QED 0.66
Compound (SMILES): CC(C)(NC(=O)c1ccc2c(c1OCCCCc1ccccc1)CCCC2)C(=O)O
InChIKey: UUEHRDAKFQMJOI-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 409.53, ALogP 4.56, HBA 3, HBD 2, PSA 75.63, QED 0.6
Compound (SMILES): CC(C)(NC(=O)c1ccc2c(c1OCCCOc1ccccc1)CCCC2)C(=O)O
InChIKey: MFKVYLDQHQTTEG-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 411.5, ALogP 4.01, HBA 4, HBD 2, PSA 84.86, QED 0.61
Compound (SMILES): CC(C)(NC(=O)c1ccc2ccsc2c1OCCCc1ccccc1)C(=O)O
InChIKey: FZZJWKALYVWTDH-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 397.5, ALogP 4.51, HBA 4, HBD 2, PSA 75.63, QED 0.55
Compound (SMILES): CC(C)(NC(=O)c1ccc2ccsc2c1OCCOc1ccc(F)cc1)C(=O)O
InChIKey: UPFZIKCYEGCTTD-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 417.46, ALogP 4.09, HBA 5, HBD 2, PSA 84.86, QED 0.54
Compound (SMILES): CC(C)(NC(=O)c1ccc2sccc2c1OCCOc1ccccc1)C(=O)O
InChIKey: DXQGCBPPBDAFTJ-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 399.47, ALogP 3.95, HBA 5, HBD 2, PSA 84.86, QED 0.56
Compound (SMILES): CC(=O)Oc1ccccc1CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
InChIKey: STSDXVAFJXUREA-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 396.44, ALogP 4.69, HBA 5, HBD 1, PSA 68.29, QED 0.37
Compound (SMILES): O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2O)nc1
InChIKey: ZXYNKZSKWUHEAX-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 438.4, ALogP 5.37, HBA 5, HBD 2, PSA 71.45, QED 0.4
Compound (SMILES): CC(=O)Oc1ccc(OC(F)(F)F)cc1CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
InChIKey: CNXMGPZISCYHMY-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 480.44, ALogP 5.59, HBA 6, HBD 1, PSA 77.52, QED 0.21