lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccccc4)nc32)c1
InChIKey: DYLDTESCOKKPMG-KPKJPENVSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 441.5, ALogP 2.98, HBA 8, HBD 2, PSA 105.04, QED 0.42
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccccc4)nc32)cc1
InChIKey: SKEYVRLMSNIOGI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 384.4, ALogP 3.04, HBA 7, HBD 2, PSA 101.8, QED 0.51
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccccc4)nc32)c1
InChIKey: CMZKQVFPFYPHOD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 5.28 nM (pChEMBL 8.279999732971191)
Descriptors: MW 384.4, ALogP 3.04, HBA 7, HBD 2, PSA 101.8, QED 0.51
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)CC
InChIKey: WIBSCJFYXUIBMU-DEMLLOIYSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of Cy5-pNPY from human Y2 receptor expressed in CHO cells after 90 to 120 mins by flow cytometry
Measurement: Ki = 1506 nM (pChEMBL 5.820000171661377)
Descriptors: MW 1673.95
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)CC
InChIKey: LTZAFDDHKCKLIF-OQXRNXRFSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 1658.98
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)CC
InChIKey: WJRYMJNKIVAKDN-CFKZHZCKSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Partial agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 1656.96
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)CC
InChIKey: GURBWRRZZPRYPX-BDNVQPKVSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 1642.94
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(N)=O)C1(C)C)[C@@H](C)O)[C@@H](C)CC
InChIKey: XMKFOZJSGUOBPD-UEKNBPOFSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of Cy5-[K4]hPP from human Y4 receptor expressed in CHO cells after 90 to 120 mins by flow cytometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 1670.99
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)CC
InChIKey: WHYFKXFBZWHHNF-JHBAXKEZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 1667
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: DIGGMVXZKSXPPQ-PCPOAYKLSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 1681.98
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](N)Cc1ccc(O)cc1
InChIKey: AMGVRRIOIXRWBL-YOGANYHLSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of Cy5-[K4]hPP from human Y4 receptor expressed in CHO cells after 90 to 120 mins by flow cytometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 4153.77
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H]1C[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]2C[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(N)=O)C2(C)C)C1(C)C)[C@@H](C)CC
InChIKey: MTFGLKCUHOHWPI-ZEOIPKQCSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 1695.06
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: CGXFKTPQEYTPLQ-BZGDUZLMSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Partial agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 1661.98
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: HWIYZQDAFNEMLJ-DSKWLTCVSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 1676.01
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: HFEQQGRFKOONEQ-GVHBCULVSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 284 nM (pChEMBL 6.550000190734863)
Descriptors: MW 1661.98
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: HLMWFNBOZLAPKN-MSYCJHJPSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 1662.93
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: NTWPZMVJPHWOPJ-YUDYGECGSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 748.89, ALogP -3.18, HBA 10, HBD 14, PSA 352.85, QED 0.03
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: DVFMZXMRSBGZSI-MPAKYALESA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 451 nM (pChEMBL 6.349999904632568)
Descriptors: MW 746.87, ALogP -3.43, HBA 10, HBD 14, PSA 352.85, QED 0.03
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: RMPKMDWFHGGGRV-QKUYTOGTSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of Cy5-pNPY from human Y1 receptor expressed in HEL cells after 90 to 120 mins by flow cytometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 810.96, ALogP -1.62, HBA 10, HBD 14, PSA 352.85, QED 0.03
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: NOEROLAGMBMTEL-KLLDHOPQSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in sf9 cells assessed as hydrolysis of [gamma-33P]GTP after 2 mins by scintillation counting analysis
Measurement: EC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 808.94, ALogP -1.86, HBA 10, HBD 14, PSA 352.85, QED 0.04
Compound (SMILES): COc1ccc(/N=c2\oc3cc(O)ccc3cc2C(=O)NCc2ccccc2)cc1
InChIKey: QEQGIVVMPNNCOY-LCUIJRPUSA-N
Target: Aldo-keto reductase family 1 member B10 (SINGLE PROTEIN), Homo sapiens
UniProt: O60218
Assay: Competitive inhibition of human recombinant AKR1B10 Q303S mutant expressed in Escherichia coli using geraniol as substrate by double-reciprocal plot analysis in presence of NADP+
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 400.43, ALogP 4.31, HBA 5, HBD 2, PSA 84.06, QED 0.52
Compound (SMILES): O=P(O)(O)C(Nc1cccc2ccccc12)P(=O)(O)O
InChIKey: MDQNHUVXMAEAFD-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 317.17, ALogP 1.89, HBA 3, HBD 5, PSA 127.09, QED 0.54
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccccc2)cc1)P(=O)(O)O
InChIKey: GPHBFHLZRQMFLJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.21, ALogP 2.53, HBA 4, HBD 5, PSA 136.32, QED 0.5
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccc(Cl)cc2)cc1)P(=O)(O)O
InChIKey: VRCNSKZUURJQAN-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 393.66, ALogP 3.18, HBA 4, HBD 5, PSA 136.32, QED 0.47
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccc(Br)cc2)cc1)P(=O)(O)O
InChIKey: ZSBBJNVNCGRSOS-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.11, ALogP 3.29, HBA 4, HBD 5, PSA 136.32, QED 0.43
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Cl)c(Cl)c1)P(=O)(O)O
InChIKey: ADHSWFUIIRWNHD-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336, ALogP 2.04, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=[N+]([O-])c1cc(NC(P(=O)(O)O)P(=O)(O)O)ccc1F
InChIKey: GSMGLRFAXIPFLS-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 330.1, ALogP 0.78, HBA 5, HBD 5, PSA 170.23, QED 0.3
Compound (SMILES): O=P(O)(O)C(Nc1cccc(C(F)(F)F)c1)P(=O)(O)O
InChIKey: SENUMOHBDKDZCG-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 20800 nM (pChEMBL 4.679999828338623)
Descriptors: MW 335.11, ALogP 1.76, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=P(O)(O)C(Nc1cccc(F)c1)P(=O)(O)O
InChIKey: SCLGFWTXZFUITP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 8687 nM (pChEMBL 5.059999942779541)
Descriptors: MW 285.1, ALogP 0.88, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): N#Cc1ccc(NC(P(=O)(O)O)P(=O)(O)O)cc1
InChIKey: ZEZSYIYQVUYORL-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 292.12, ALogP 0.61, HBA 4, HBD 5, PSA 150.88, QED 0.51
Compound (SMILES): O=P(O)(O)C(Nc1ccc(O)cc1)P(=O)(O)O
InChIKey: XQVNOYYFZWUDCV-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 283.11, ALogP 0.44, HBA 4, HBD 6, PSA 147.32, QED 0.34
Compound (SMILES): Cc1ccc(NC(P(=O)(O)O)P(=O)(O)O)cc1
InChIKey: FVJHDPVFVSTFKH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 281.14, ALogP 1.05, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): O=P(O)(O)C(Nc1ccc(C(F)(F)F)cc1)P(=O)(O)O
InChIKey: RBHODZPTKHWXDX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 335.11, ALogP 1.76, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Br)cc1)P(=O)(O)O
InChIKey: AXIAQHKDCQVIKV-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 346.01, ALogP 1.5, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): CCc1cc2c(c(CC)n1)CCC(=O)N2Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1.Cl
InChIKey: NAGGAAHTUXEGFG-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: PDSP Secondary Binding target: OPRM1 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 6269.02 nM (pChEMBL 5.199999809265137)
Descriptors: MW 438.54, ALogP 4.53, HBA 5, HBD 1, PSA 87.66, QED 0.48
Compound (SMILES): O=[N+]([O-])c1ccc(NC(P(=O)(O)O)P(=O)(O)O)cc1
InChIKey: HTWBLJFKBSZUAN-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 312.11, ALogP 0.65, HBA 5, HBD 5, PSA 170.23, QED 0.3
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Cl)cc1)P(=O)(O)O
InChIKey: PPOZCMYPJMEBPT-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 301.56, ALogP 1.39, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=P(O)(O)C(Nc1ccccc1)P(=O)(O)O
InChIKey: XVNZXEWQQDCZSM-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 437 nM (pChEMBL 6.360000133514404)
Descriptors: MW 267.11, ALogP 0.74, HBA 3, HBD 5, PSA 127.09, QED 0.51
Compound (SMILES): O=P(O)(O)C(Nc1ccc(F)cc1)P(=O)(O)O
InChIKey: CXOBNZQSLVRTMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 285.1, ALogP 0.88, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): O=C(Nc1nc(C(F)(F)F)cs1)c1cc(F)cc(Oc2cncnc2)c1
InChIKey: QFGZDSNEPZPSFG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 4040 nM (pChEMBL 5.389999866485596)
Descriptors: MW 384.31, ALogP 4.14, HBA 6, HBD 1, PSA 77, QED 0.68
Compound (SMILES): O=C(Nc1cc(Cl)ccn1)c1cc(F)cc(Oc2cncnc2)c1
InChIKey: WVEHLASNLHISFH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 344.73, ALogP 3.71, HBA 5, HBD 1, PSA 77, QED 0.78
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)ccn1)c1cc(F)cc(Oc2cncnc2)c1
InChIKey: XBWJPFZNCGVCJM-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 378.29, ALogP 4.07, HBA 5, HBD 1, PSA 77, QED 0.69
Compound (SMILES): O=C(Nc1cc(F)ccn1)c1cc(Cl)cc(Oc2cncnc2)c1
InChIKey: LBLUQLJKQZGYIW-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 344.73, ALogP 3.71, HBA 5, HBD 1, PSA 77, QED 0.78
Compound (SMILES): O=C(Nc1cccc(F)n1)c1cc(Cl)cc(Oc2cncnc2)c1
InChIKey: FCGGFIQFAJSREN-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 344.73, ALogP 3.71, HBA 5, HBD 1, PSA 77, QED 0.73
Compound (SMILES): O=C(Nc1cccc(Cl)n1)c1cc(Cl)cc(Oc2cncnc2)c1
InChIKey: BUIOHRKCCSCORH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 361.19, ALogP 4.22, HBA 5, HBD 1, PSA 77, QED 0.7
Compound (SMILES): COc1cccc(NC(=O)c2cc(Cl)cc(Oc3cncnc3)c2)n1
InChIKey: ABUZOTKQQBPGAC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 356.77, ALogP 3.58, HBA 6, HBD 1, PSA 86.23, QED 0.75
Compound (SMILES): Cc1csc(NC(=O)c2cc(F)cc(Oc3cncnc3)c2)n1
InChIKey: AXVLPJHYYFHCHK-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Negative allosteric modulation of rat mGlu5 receptor expressed in HEK293A cells assessed as inhibition of glutamate-induced calcium mobilization preincubated for 140 seconds prior to glutamate-stimulation measured after 60 seconds
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 330.34, ALogP 3.43, HBA 6, HBD 1, PSA 77, QED 0.79
Compound (SMILES): Cc1csc(NC(=O)c2cc(Cl)cc(Oc3cncnc3)c2)n1
InChIKey: JBUDGQFEYJAIBH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Negative allosteric modulation of rat mGlu5 receptor expressed in HEK293A cells assessed as inhibition of glutamate-induced calcium mobilization preincubated for 140 seconds prior to glutamate-stimulation measured after 60 seconds
Measurement: IC50 = 11.48 nM (pChEMBL 7.940000057220459)
Descriptors: MW 346.8, ALogP 3.94, HBA 6, HBD 1, PSA 77, QED 0.77
Compound (SMILES): O=C(Nc1ccc(F)cn1)c1cc(Cl)cc(Oc2cncnc2)c1
InChIKey: GAENEKJGLXICIO-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31424
Assay: Metabotropic Glutamate Receptor Activity Assay: The utility of the compounds in accordance with the present invention as negative allosteric modulators of metabotropic glutamate receptor activity, in particular mGluR5 activity, can be demonstrated by methodology known in the art. Human embryonic kidney (HEK) cells transfected with rat or human mGluR5 were plated in clear bottom assay plates for assay in a Functional Drug Screening System (FDSS). The cells were loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4), and the plates were washed and placed in the FDSS instrument. Test compound was applied to cells 3 seconds after baseline readings were taken. Cells were incubated with the test compounds for 140 seconds and then stimulated with an EC20 concentration of an mGluR5 agonist (e.g., glutamate, 3,5-dihydroxyphenylglycine, or quisqualate); 60-80 seconds later an EC80 concentration of agonist was added and readings taken for an additional 40 seconds. Data were collected at 1 Hz. Negative allosteric modulation of the agonist.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 344.73, ALogP 3.71, HBA 5, HBD 1, PSA 77, QED 0.78
Compound (SMILES): CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](O)C[C@]12C
InChIKey: BFZHCUBIASXHPK-ATWVFEABSA-N
Target: 11-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P80365
Assay: Inhibition of human recombinant 11beta-HSD2 expressed in HEK293 cells assessed as inhibition of [1,2,6,7-3H]-cortisol to [3H]cortisone preincubated for 10 mins before substrate addition by scintillation counting
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 330.47, ALogP 3.69, HBA 3, HBD 1, PSA 54.37, QED 0.8
Compound (SMILES): NCCCOCCOCCOCCNC(=O)CCC(=O)NCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: DOLVYXIAWXUFAZ-JFRIYMKVSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 904.08, ALogP 0.59, HBA 10, HBD 10, PSA 304.74, QED 0.02
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(=O)NCCCCNC(=O)CNC(=O)CCC(=O)NCCN(CCN)CCNC(=O)CCC(=O)NCC(=O)NCCCCNC(=O)NCc2ccc(CNC(=O)[C@@H](CCCNC(=N)N)NC(=O)C(c3ccccc3)c3ccccc3)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: RSHSYTFSXZEIOX-UKLKETJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 1625.99
Compound (SMILES): NCCN(CCNC(=O)CCC(=O)NCCCCCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)CC1(CC(=O)N2CCN(C3c4ccccc4NC(=O)c4ccccc43)CC2)CCCC1)C(=O)NCCn1c(=O)n(-c2ccccc2)n(-c2ccccc2)c1=O)CCNC(=O)CCC(=O)NCCCCCCNC(=O)/N=C(\N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: VUNSOCGMBRUSCG-FRMZLZDCSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 1964.4
Compound (SMILES): NCCC(=O)NCCNC(=O)CCC(=O)NCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: FKLPZFXVYBYMIS-UCRKPPETSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 828.98, ALogP -0.34, HBA 8, HBD 11, PSA 306.15, QED 0.03
Compound (SMILES): NCCNC(=O)CCC(=O)NCCNC(=O)CCC(=O)NCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: VWSWQPAVQMMCPT-GXUZKUJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 900.06, ALogP -0.83, HBA 9, HBD 12, PSA 335.25, QED 0.03
Compound (SMILES): NCCC(=O)NCCNC(=O)CCC(=O)NCCNC(=O)CCC(=O)NCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: RYLWAKKPBHUCLE-KGLWNCEWSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 971.13, ALogP -1.33, HBA 10, HBD 13, PSA 364.35, QED 0.02
Compound (SMILES): NCCOCCOCCNC(=O)CCC(=O)NCCNC(=O)/N=C(\N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: DFFWMMJLBLFNAV-GXUZKUJRSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 3200 nM (pChEMBL 5.5)
Descriptors: MW 846, ALogP 0.19, HBA 9, HBD 10, PSA 295.51, QED 0.03
Compound (SMILES): NCCN(CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1)CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: LBODTNMZCCOGSK-UDCAZBBNSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 1718.04
Compound (SMILES): NCCN(CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1)CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(N)=O)cc1.O=C(O)C(F)(F)F
InChIKey: LBODTNMZCCOGSK-QBZSOHMWSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 1718.04
Compound (SMILES): NCCN(CCNC(=O)c1ccc(C(=O)NCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1)CCNC(=O)c1ccc(C(=O)NCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: FRMILORZHWVZRG-SFDIVQKFSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 1581.89
Compound (SMILES): NCCN(CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1)CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: YLYCSRLIHWNYMU-NQIIEAPRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human MCF7 cells
Measurement: Ki = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 1702
Compound (SMILES): NCCN(CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1)CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: YLYCSRLIHWNYMU-KHWXROTFSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Binding affinity to human neuropeptide Y receptor type 4 receptor expressed in CHO cells using Cy5-[K4]-hPP by flow cytometric analysis
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 1702
Compound (SMILES): CCC(=O)NCCN(CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1)CCNC(=O)c1ccc(C(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)NCc2ccc(O)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: PXNWBWKPLQHYRI-RZYNTDKESA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human MCF7 cells
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 1758.06
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(CNC(=O)NCCCCNC(=O)CCCC(=O)NCCN(CCN)CCNC(=O)CCCC(=O)NCCCCNC(=O)NCc2ccc(CNC(=O)[C@@H](CCCNC(=N)N)NC(=O)C(c3ccccc3)c3ccccc3)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: VGLAKDPLQDLNLW-UKLKETJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human MCF7 cells
Measurement: Ki = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 1539.94
Compound (SMILES): NCCN(CCNC(=O)CCCC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1)CCNC(=O)CCCC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1
InChIKey: VTTARGWCWRDOCN-YZCGSYMESA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 1285.56
Compound (SMILES): NCCN(CCNC(=O)CCC(=O)NCCCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1)CCNC(=O)CCC(=O)NCCCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: KTDUOPZXELVWII-UKLKETJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 1541.91
Compound (SMILES): NCCN(CCNC(=O)CCCCC(=O)NCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1)CCNC(=O)CCCCC(=O)NCCCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: NPHSKAKDPVIVPI-UKLKETJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 1541.91