lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)OC(=O)N1CC(COc2ccc(Cc3cc([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)ccc3Cl)cc2)C1
InChIKey: XDAYPZNILNASKX-RTJMFUJLSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 2755 nM (pChEMBL 5.559999942779541)
Descriptors: MW 550.05, ALogP 2.69, HBA 8, HBD 4, PSA 128.92, QED 0.41
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCC4CNC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: BHGXASLBRNBSPJ-ZQGJOIPISA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 785 nM (pChEMBL 6.110000133514404)
Descriptors: MW 449.93, ALogP 1.04, HBA 7, HBD 5, PSA 111.41, QED 0.43
Compound (SMILES): CN1CC(COc2ccc(Cc3cc([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)ccc3Cl)cc2)C1
InChIKey: GFRIHFQPVDLSGC-SJSRKZJXSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 1464 nM (pChEMBL 5.829999923706055)
Descriptors: MW 463.96, ALogP 1.39, HBA 7, HBD 4, PSA 102.62, QED 0.49
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(CC4(F)COC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: GDTAXKPFLMCLKC-BDHVOXNPSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 2478 nM (pChEMBL 5.610000133514404)
Descriptors: MW 452.91, ALogP 1.73, HBA 6, HBD 4, PSA 99.38, QED 0.53
Compound (SMILES): CC(=O)N1CC(COc2ccc(Cc3cc([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)ccc3Cl)cc2)C1
InChIKey: XRSHIDNAPGODDP-RXFVIIJJSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 469 nM (pChEMBL 6.329999923706055)
Descriptors: MW 491.97, ALogP 1.3, HBA 7, HBD 4, PSA 119.69, QED 0.46
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCC4CN(C5COC5)C4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: CTBKTGMPGONTDS-RTJMFUJLSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 2451 nM (pChEMBL 5.610000133514404)
Descriptors: MW 506, ALogP 1.16, HBA 8, HBD 4, PSA 111.85, QED 0.42
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCC4CN(c5ccc(F)cc5)C4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: ODDVSPVKEFCORY-RQKPWJHBSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 97.2 nM (pChEMBL 7.010000228881836)
Descriptors: MW 544.02, ALogP 3.1, HBA 7, HBD 4, PSA 102.62, QED 0.35
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCC4(CF)COC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: FFESYXGUALEKFZ-ZQGJOIPISA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 482.93, ALogP 1.81, HBA 7, HBD 4, PSA 108.61, QED 0.45
Compound (SMILES): CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c(OCCCC3(F)COC3)cc2Cl)cc1
InChIKey: RQRBSJVEMCAMNY-RTJMFUJLSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 541.01, ALogP 2.74, HBA 8, HBD 4, PSA 117.84, QED 0.32
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCC4CCO4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: MTFDMGPHMDXIIT-WLNBBENOSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 450.92, ALogP 1.61, HBA 7, HBD 4, PSA 108.61, QED 0.51
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCCCC4COC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: LSJZCDRZEPSGEQ-RXFVIIJJSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 478.97, ALogP 2.25, HBA 7, HBD 4, PSA 108.61, QED 0.41
Compound (SMILES): OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(OCCCC4(F)COC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: BCHNVDSGXFJQJL-SJSRKZJXSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 496.96, ALogP 2.34, HBA 7, HBD 4, PSA 108.61, QED 0.39
Compound (SMILES): CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c(OCC3(F)COC3)cc2Cl)cc1
InChIKey: PNFDVSZDYRTJLQ-SJSRKZJXSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 512.96, ALogP 1.96, HBA 8, HBD 4, PSA 117.84, QED 0.4
Compound (SMILES): CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c(OCC3CNC3)cc2Cl)cc1
InChIKey: UTDBAYORDQIJGX-RXFVIIJJSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Uptake Assay: A cDNA clone expressing human SGLT1/SGLT2 was bought from GenerScript. Having the sequence information, it was built into pcDNA5 carrier by using traditional molecular biology methods, and then the expression plasmids were transfected into Flp-in CHO cells by using Lipofetamin 200 liposomal transfection method. The transfected cells were screened for hygromycin resistance, and the single-cell clone was screened out through the process of gradient dilution. Having obtained the single-cell clone, the uptake assay of 14C-AMG in FLP-in CHO cells stably expressing SGLT1/SGLT2 was evaluated.Cells were seeded at a density of 3x104 cells per well, uptake assay was carried out after adherent cells were cultured overnight. At least 12 hours later of culture, cells were washed once by 150 microliters per well of the absorption solution KRH-NMG (120 mM NMG, 4.7 mM KCl, 1.2 mM MgCl2, 2.2 mM CaCl2, 10 mM HEPES, pH 7.4 with HCl). To every well that was cleaned with buffer KRH-Na+ and KRH-NMG.
Measurement: IC50 = 69.4 nM (pChEMBL 7.159999847412109)
Descriptors: MW 493.98, ALogP 1.44, HBA 8, HBD 5, PSA 120.64, QED 0.36
Compound (SMILES): CCN(Cc1ccccc1)C(=O)Cc1c(-c2ccc(Cl)cc2)nc2cc(C)ccn12
InChIKey: ZKXBCTBEVJXSSK-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 7.17 nM (pChEMBL 8.140000343322754)
Descriptors: MW 417.94, ALogP 5.55, HBA 3, HBD 0, PSA 37.61, QED 0.41
Compound (SMILES): CCN(Cc1ccccc1)C(=O)Cc1c(-c2ccc(Cl)c(Cl)c2)nc2cc(C)ccn12
InChIKey: OBCXJDCPGARBPX-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 49.19 nM (pChEMBL 7.309999942779541)
Descriptors: MW 452.39, ALogP 6.21, HBA 3, HBD 0, PSA 37.61, QED 0.35
Compound (SMILES): CCN(Cc1ccccn1)C(=O)Cc1c(-c2ccc(Cl)c(Cl)c2)nc2cc(C)ccn12
InChIKey: ILPWQHIEKZASOY-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 9.34 nM (pChEMBL 8.029999732971191)
Descriptors: MW 453.37, ALogP 5.6, HBA 4, HBD 0, PSA 50.5, QED 0.38
Compound (SMILES): CCN(Cc1ccncc1)C(=O)Cc1c(-c2ccc(Cl)c(Cl)c2)nc2cc(C)ccn12
InChIKey: WXCBACASSXWEFP-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 11.09 nM (pChEMBL 7.960000038146973)
Descriptors: MW 453.37, ALogP 5.6, HBA 4, HBD 0, PSA 50.5, QED 0.38
Compound (SMILES): COCCN(Cc1ccccn1)C(=O)Cc1c(-c2ccc(Cl)c(Cl)c2)nc2cc(C)ccn12
InChIKey: UEUYZNBMUXXLAY-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 6.66 nM (pChEMBL 8.180000305175781)
Descriptors: MW 483.4, ALogP 5.23, HBA 5, HBD 0, PSA 59.73, QED 0.34
Compound (SMILES): CCN(Cc1ccccc1)C(=O)Cc1c(-c2ccc(C)cc2)nc2cc(C)ccn12
InChIKey: WDNQTDRSVLELNO-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 2.97 nM (pChEMBL 8.529999732971191)
Descriptors: MW 397.52, ALogP 5.21, HBA 3, HBD 0, PSA 37.61, QED 0.45
Compound (SMILES): CCN(Cc1ccccn1)C(=O)Cc1c(-c2ccc(C)cc2)nc2cc(C)ccn12
InChIKey: AUNINMCWJJJEJY-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Competitive Binding Assay: Competitive Binding Test of Drug to the Receptor (Rat Heart TSPO) and Radioligand (3H-PK11195): (1) tubes were placed in reaction condition of 30 C.(2) all tubes were added with 20 ug of receptor protein in order;(3) the test tubes were added in order with 20 uL of drugs in certain concentrations;(4) the non-specific binding tubes were added with 20 uL of non-tagged ligand (PK11195), the final concentration of the non-tagged ligand was 0.1 mM, pre-reacted for 30 min;(5) all tubes were added in order with 25 uL 3H-PK11195, the final concentration of the labeled ligand was 1.5 nM;(6) Tris-HCl Buffer pH7.4 was used to complement the reaction volumes of all tubes to reach 200 uL;(7) the reaction was performed under 30 C. reaction condition for 1 h;(8) Then samples were applied to 49-type glass fibre filter, vacuum suction filtered, then washed with 2 ml ice-cold Tris-HCl buffer solution (50 mM Tris-HCl buffer solution, 1 mM EDTA, 5 mM MgCl2, 1 mM PMSF, 0.1% NaN3.
Measurement: Ki = 38.73 nM (pChEMBL 7.409999847412109)
Descriptors: MW 398.51, ALogP 4.6, HBA 4, HBD 0, PSA 50.5, QED 0.48
Compound (SMILES): Cc1c[nH]c2ncnc(NC(C)c3nc4cccc(C)c4c(=O)n3-c3cccc(F)c3)c12
InChIKey: ZWCUNRDFHRJPJI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: Using the method described in Example 2, compounds of the invention were tested for inhibitory activity and potency against PI3Kdelta, and for selectivity for PI3Kdelta versus other Class I PI3K isozymes. In Table 1, IC50 values (uM) are given for PI3Kdelta (Delta), and may be calculated for the other isoforms using the ratios of IC50 values discussed below. To illustrate selectivity of the compounds, the ratios of the IC50 values of the compounds for PI3Kalpha, PI3Kbeta, and PI3Kgamma relative to PI3Kdelta are given, respectively, as Alpha/Delta Ratio, Beta/Delta Ratio, and Gamma/Delta Ratio.The initial selectivity assays were performed identically to the selectivity assay protocol in Example 2, except, using 100 uL Ecosint for radiolabel detection. Subsequent selectivity assays were done similarly using the same 3 substrate stocks except they contained 0.05 mCi/mL gamma [32P] ATP and 3 mM PIP2. Subsequent selectivity assays also used the same 3 enzyme stocks.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 428.47, ALogP 4.59, HBA 6, HBD 2, PSA 88.49, QED 0.44
Compound (SMILES): C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccccc2c(=O)n1-c1cccc(F)c1
InChIKey: RATYHMNWOPJSLV-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: Using the method described in Example 2, compounds of the invention were tested for inhibitory activity and potency against PI3Kdelta, and for selectivity for PI3Kdelta versus other Class I PI3K isozymes. In Table 1, IC50 values (uM) are given for PI3Kdelta (Delta), and may be calculated for the other isoforms using the ratios of IC50 values discussed below. To illustrate selectivity of the compounds, the ratios of the IC50 values of the compounds for PI3Kalpha, PI3Kbeta, and PI3Kgamma relative to PI3Kdelta are given, respectively, as Alpha/Delta Ratio, Beta/Delta Ratio, and Gamma/Delta Ratio.The initial selectivity assays were performed identically to the selectivity assay protocol in Example 2, except, using 100 uL Ecosint for radiolabel detection. Subsequent selectivity assays were done similarly using the same 3 substrate stocks except they contained 0.05 mCi/mL gamma [32P] ATP and 3 mM PIP2. Subsequent selectivity assays also used the same 3 enzyme stocks.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 401.41, ALogP 3.36, HBA 7, HBD 2, PSA 101.38, QED 0.48
Compound (SMILES): CC(Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cc2c(=O)n1-c1cc(F)cc(F)c1
InChIKey: OWTMTJWDZILAMW-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: Using the method described in Example 2, compounds of the invention were tested for inhibitory activity and potency against PI3Kdelta, and for selectivity for PI3Kdelta versus other Class I PI3K isozymes. In Table 1, IC50 values (uM) are given for PI3Kdelta (Delta), and may be calculated for the other isoforms using the ratios of IC50 values discussed below. To illustrate selectivity of the compounds, the ratios of the IC50 values of the compounds for PI3Kalpha, PI3Kbeta, and PI3Kgamma relative to PI3Kdelta are given, respectively, as Alpha/Delta Ratio, Beta/Delta Ratio, and Gamma/Delta Ratio.The initial selectivity assays were performed identically to the selectivity assay protocol in Example 2, except, using 100 uL Ecosint for radiolabel detection. Subsequent selectivity assays were done similarly using the same 3 substrate stocks except they contained 0.05 mCi/mL gamma [32P] ATP and 3 mM PIP2. Subsequent selectivity assays also used the same 3 enzyme stocks.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 437.39, ALogP 3.64, HBA 7, HBD 2, PSA 101.38, QED 0.45
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ccccc2)cc1Cl
InChIKey: ZVFQOEWWGMBCJW-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 = 0.1721 nM (pChEMBL 9.760000228881836)
Descriptors: MW 464.95, ALogP 4.1, HBA 6, HBD 1, PSA 76.58, QED 0.54
Compound (SMILES): COc1ccc(COc2nc(N3C4CCC3COC4)ncc2C(=O)NCc2ccccc2)cc1Cl
InChIKey: JPJYLAXQZSQSKA-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 = 4.013 nM (pChEMBL 8.399999618530273)
Descriptors: MW 494.98, ALogP 4.02, HBA 7, HBD 1, PSA 85.81, QED 0.51
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ncccn2)cc1Cl
InChIKey: ZNPNIDSHHUSEAF-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 = 0.1 nM (pChEMBL 10)
Descriptors: MW 466.93, ALogP 2.89, HBA 8, HBD 1, PSA 102.36, QED 0.54
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ccccn2)cc1Cl
InChIKey: JERZAFZAPCLCBQ-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 = 0.028 nM (pChEMBL 10.550000190734863)
Descriptors: MW 465.94, ALogP 3.5, HBA 7, HBD 1, PSA 89.47, QED 0.54
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCc2cnc(C)cn2)cc1Cl
InChIKey: AMBRYILSQYFVJA-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 = 0.5287 nM (pChEMBL 9.279999732971191)
Descriptors: MW 480.96, ALogP 3.2, HBA 8, HBD 1, PSA 102.36, QED 0.52
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ccc(F)cc2)cc1Cl
InChIKey: RWUZHHNNVVOHSY-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 = 0.075 nM (pChEMBL 10.119999885559082)
Descriptors: MW 482.94, ALogP 4.24, HBA 6, HBD 1, PSA 76.58, QED 0.52
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)N[C@H]2CC[C@H](O)CC2)cc1Cl
InChIKey: HTHPJFXWRQIPGG-VNGAXPGBSA-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 = 0.7389 nM (pChEMBL 9.130000114440918)
Descriptors: MW 472.97, ALogP 3.21, HBA 7, HBD 2, PSA 96.81, QED 0.64
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC3)CC4)ncc2C(=O)NCc2ncccn2)cc1Cl
InChIKey: TWOKSRWWJTWZEF-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 = 0.4765 nM (pChEMBL 9.319999694824219)
Descriptors: MW 494.98, ALogP 3.82, HBA 8, HBD 1, PSA 102.36, QED 0.5
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC3)CC4)ncc2C(=O)NCc2ccccn2)cc1Cl
InChIKey: XAXNQDDRESESHR-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 = 0.1858 nM (pChEMBL 9.729999542236328)
Descriptors: MW 494, ALogP 4.42, HBA 7, HBD 1, PSA 89.47, QED 0.5
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC3)CC4)ncc2C(=O)NCc2ccccc2)cc1Cl
InChIKey: XDBYPEYXXFSOGX-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 = 1.14 nM (pChEMBL 8.9399995803833)
Descriptors: MW 493.01, ALogP 5.03, HBA 6, HBD 1, PSA 76.58, QED 0.48
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC3)CC4)ncc2C(=O)NCCN2CCOCC2)cc1Cl
InChIKey: IRTPYMJZECXOTO-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 = 0.9353 nM (pChEMBL 9.029999732971191)
Descriptors: MW 516.04, ALogP 3.16, HBA 8, HBD 1, PSA 89.05, QED 0.54
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC3)CC4)ncc2C(=O)N[C@H]2CC[C@H](O)CC2)cc1Cl
InChIKey: ZOARRCZXCGKMCU-WGSAOQKQSA-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 = 0.719 nM (pChEMBL 9.140000343322754)
Descriptors: MW 501.03, ALogP 4.13, HBA 7, HBD 2, PSA 96.81, QED 0.59
Compound (SMILES): COc1ccc(COc2nc(N3CC4CC4C3)ncc2C(=O)NCCN2CCOCC2)cc1Cl
InChIKey: JYBJUPMUDXKESZ-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 = 0.2127 nM (pChEMBL 9.670000076293945)
Descriptors: MW 487.99, ALogP 2.24, HBA 8, HBD 1, PSA 89.05, QED 0.58
Compound (SMILES): COc1ccc(COc2nc(N3CCCC34CC4)ncc2C(=O)NCc2ccccc2)cc1Cl
InChIKey: UJEPTGGPULNKJX-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 = 1.976 nM (pChEMBL 8.699999809265137)
Descriptors: MW 478.98, ALogP 4.78, HBA 6, HBD 1, PSA 76.58, QED 0.5
Compound (SMILES): COc1ccc(COc2nc(N3CCC4(CC4)C3)ncc2C(=O)NCc2ccccc2)cc1Cl
InChIKey: OTAQSGAVWQKRBH-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 = 0.1188 nM (pChEMBL 9.930000305175781)
Descriptors: MW 478.98, ALogP 4.64, HBA 6, HBD 1, PSA 76.58, QED 0.51