lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc(C(=O)N5CCOCC5)cc4)c(-c4ccncc4)n3n2)CC1
InChIKey: PTFDQIBTFLXUAW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of human recombinant haspin kinase domain expressed in Escherichia coli BL21-KRX using histone H3 (1 to 21) peptide substrate after 30 mins by scintillation and luminescence counting method in the presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.58, ALogP 2.68, HBA 8, HBD 0, PSA 79.1, QED 0.44
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc(C(=O)N5CCOCC5)c4)c(-c4ccncc4)n3n2)CC1
InChIKey: IXHPWOYBNAVCPP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of human recombinant haspin kinase domain expressed in Escherichia coli BL21-KRX using histone H3 (1 to 21) peptide substrate after 30 mins by scintillation and luminescence counting method in the presence of [gamma-33P]ATP
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 483.58, ALogP 2.68, HBA 8, HBD 0, PSA 79.1, QED 0.44
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5c4OCO5)c(-c4cccnc4)n3n2)CC1
InChIKey: JXSPMVJUQGQTOQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of human recombinant CDK5/P25 expressed in Escherichia coli using histone H1 substrate after 30 mins by scintillation and luminescence counting method in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.47, ALogP 2.94, HBA 8, HBD 0, PSA 68.02, QED 0.51
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5c4OCO5)c(-c4ccccc4)n3n2)CC1
InChIKey: UUFIIKREBUVIMW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of human recombinant CDK5/P25 expressed in Escherichia coli using histone H1 substrate after 30 mins by scintillation and luminescence counting method in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.48, ALogP 3.54, HBA 7, HBD 0, PSA 55.13, QED 0.51
Compound (SMILES): c1cc2c(c(-c3nc4cccnn4c3-c3ccncc3)c1)OCO2
InChIKey: MBSLKTPFDORDOH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of human recombinant CDK5/P25 expressed in Escherichia coli using histone H1 substrate after 30 mins by scintillation and luminescence counting method in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 316.32, ALogP 3.19, HBA 6, HBD 0, PSA 61.54, QED 0.57
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5c4OCO5)c(-c4ccncc4)n3c2)CC1
InChIKey: WFAGOLWNQFGARG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of human recombinant CDK5/P25 expressed in Escherichia coli using histone H1 substrate after 30 mins by scintillation and luminescence counting method in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.48, ALogP 3.54, HBA 7, HBD 0, PSA 55.13, QED 0.51
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(CCC(=O)O)CC3)c2c1
InChIKey: LCLFVSWORFRMBJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Competitive inhibition of human recombinant GSK-3beta after 60 mins by microfluidic assay in presence of ATP
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 360.41, ALogP 1.49, HBA 5, HBD 3, PSA 107.55, QED 0.69
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(CCCC(=O)O)CC3)c2c1
InChIKey: SHQBCBFQEAZMRA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 374.44, ALogP 1.88, HBA 5, HBD 3, PSA 107.55, QED 0.65
Compound (SMILES): CCC(=O)NCCCN1CCC(CNC(=O)c2n[nH]c3ccc(OC)cc23)CC1
InChIKey: FBAFAVQZISHCJM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 401.51, ALogP 1.93, HBA 5, HBD 3, PSA 99.35, QED 0.56
Compound (SMILES): CCCC(=O)NCCCN1CCC(CNC(=O)c2n[nH]c3ccc(OC)cc23)CC1
InChIKey: JGSXYTYAUFPAJT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 415.54, ALogP 2.32, HBA 5, HBD 3, PSA 99.35, QED 0.52
Compound (SMILES): C/C=C/C(=O)NCCCN1CCC(CNC(=O)c2n[nH]c3ccc(OC)cc23)CC1
InChIKey: IPEOUKRUQUAFKV-HWKANZROSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 413.52, ALogP 2.1, HBA 5, HBD 3, PSA 99.35, QED 0.43
Compound (SMILES): CC#CC(=O)NCCCN1CCC(CNC(=O)c2n[nH]c3ccc(OC)cc23)CC1
InChIKey: RSNPNQJDIOQTSQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 411.51, ALogP 1.54, HBA 5, HBD 3, PSA 99.35, QED 0.45
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(CCCNC(=O)c4ccccc4)CC3)c2c1
InChIKey: QEDSHPPMMPIPII-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 3420 nM (pChEMBL 5.46999979019165)
Descriptors: MW 449.56, ALogP 2.83, HBA 5, HBD 3, PSA 99.35, QED 0.44
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(Cc4ccc(Cl)cc4Cl)CC3)c2c1
InChIKey: YCTKWXLLTRJPAD-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 447.37, ALogP 4.52, HBA 4, HBD 2, PSA 70.25, QED 0.58
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(Cc4ccnc(C(=O)O)c4)CC3)c2c1
InChIKey: BYAMWHZYBUUWPE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 423.47, ALogP 2.31, HBA 6, HBD 3, PSA 120.44, QED 0.53
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(CCc4ccc(O)cc4)CC3)c2c1
InChIKey: SOKOQHNUYVVYND-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00536
Assay: LanthaScreen TR-FRET Assay: Compound 1 was also assayed to determine the IC50 values for three different kinases (PCTAIRE1, DYRK1a, and CDK2) in comparison to Gsk3beta. The assay was conducted with the same method described below in the second assay. Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266). In a first screening assay, compounds were tested in duplicate at a concentration of 10 Î¼M.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um).
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 408.5, ALogP 2.96, HBA 5, HBD 3, PSA 90.48, QED 0.56
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(CCC4CCCC(C)C4)CC3)c2c1
InChIKey: XOOYTHKXMQQQEA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 412.58, ALogP 4.23, HBA 4, HBD 2, PSA 70.25, QED 0.71
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(Cc4nc(C(=O)O)co4)CC3)c2c1
InChIKey: NWKSXGISQIPVIA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 413.43, ALogP 1.9, HBA 7, HBD 3, PSA 133.58, QED 0.53
Compound (SMILES): COC(=O)c1coc(CN2CCC(CNC(=O)c3n[nH]c4ccc(OC)cc34)CC2)n1
InChIKey: VKJSYJBYBSYYPO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 5170 nM (pChEMBL 5.289999961853027)
Descriptors: MW 427.46, ALogP 1.99, HBA 8, HBD 2, PSA 122.58, QED 0.55
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(Cc4nc(C(=O)O)cs4)CC3)c2c1
InChIKey: GEAOHLKIGUKERJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 429.5, ALogP 2.37, HBA 7, HBD 3, PSA 120.44, QED 0.53
Compound (SMILES): COC(=O)c1csc(CN2CCC(CNC(=O)c3n[nH]c4ccc(OC)cc34)CC2)n1
InChIKey: IFOCWYIZCJPIJY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 2130 nM (pChEMBL 5.670000076293945)
Descriptors: MW 443.53, ALogP 2.46, HBA 8, HBD 2, PSA 109.44, QED 0.54
Compound (SMILES): COc1ccc2[nH]nc(C(=O)NCC3CCN(Cc4noc(C(N)=O)n4)CC3)c2c1
InChIKey: FTNGUVUKNTWCET-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 413.44, ALogP 0.7, HBA 8, HBD 3, PSA 152.26, QED 0.51
Compound (SMILES): COC(=O)c1ccoc1CN1CCC(CNC(=O)c2n[nH]c3ccc(OC)cc23)CC1
InChIKey: JPBJGSYWESOYTD-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 426.47, ALogP 2.59, HBA 7, HBD 2, PSA 109.69, QED 0.56
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cnccc4OC)cc23)CC1
InChIKey: GOKBBVFOHCGFRN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 423.52, ALogP 2.72, HBA 6, HBD 2, PSA 92.37, QED 0.58
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cncc(OC)c4)cc23)CC1
InChIKey: CSEMNQRANZNKJH-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 423.52, ALogP 2.72, HBA 6, HBD 2, PSA 92.37, QED 0.58
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4ccc(OC)nc4)cc23)CC1
InChIKey: JTTBDQWSWBWKFD-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 423.52, ALogP 2.72, HBA 6, HBD 2, PSA 92.37, QED 0.58
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4ccc(C)nc4)cc23)CC1
InChIKey: NEKFZTHNKMNCEO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 407.52, ALogP 3.02, HBA 5, HBD 2, PSA 83.14, QED 0.63
Compound (SMILES): O=C(O)c1ccc(CN2CCC(CNC(=O)c3n[nH]c4ccc(-c5ccccc5F)cc34)CC2)o1
InChIKey: CCBLLNUPTSUBTL-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: LanthaScreen TR-FRET Assay: Activity on human GSK-3beta was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 uM.Human recombinant enzyme GSK-3beta was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA). The results, reported in the following Table 4, are expressed as a percent of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 um). In a second assay, the same compounds were assayed at five concentrations ranging from 100 uM to 10 nM with ten-fold dilutions in duplicate.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 476.51, ALogP 4.3, HBA 5, HBD 3, PSA 111.46, QED 0.37
Compound (SMILES): O=C(O)c1ccc(CN2CCC(CNC(=O)c3n[nH]c4ccc(-c5cccc(F)c5F)cc34)CC2)o1
InChIKey: OHINXHLFKNAQMY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK-3beta using Ulight-CFFKNIVTPRTPPPSQQGK-amide as substrate after 90 mins by LANCE assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 494.5, ALogP 4.44, HBA 5, HBD 3, PSA 111.46, QED 0.35
Compound (SMILES): COc1ccc(-c2ccc3[nH]nc(C(=O)NCC4CCN(Cc5ccc(C(=O)O)o5)CC4)c3c2)cn1
InChIKey: ZOFDKUGNFQINCC-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 = 70800 nM (pChEMBL 4.150000095367432)
Descriptors: MW 489.53, ALogP 3.57, HBA 7, HBD 3, PSA 133.58, QED 0.34
Compound (SMILES): O=C(O)c1coc(CN2CCC(CNC(=O)c3n[nH]c4ccc(-c5cccc(F)c5F)cc34)CC2)n1
InChIKey: XXAOHCUJHCJTGG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) expressed in CHO cells assessed as Tau phosphorylation after 2 hrs
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 495.49, ALogP 3.84, HBA 6, HBD 3, PSA 124.35, QED 0.36
Compound (SMILES): CCc1ccc2[nH]nc(C(=O)NCC3CCN(CC(=O)O)CC3)c2c1
InChIKey: SVENVMQUIGXOCN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 960 nM (pChEMBL 6.019999980926514)
Descriptors: MW 344.42, ALogP 1.65, HBA 4, HBD 3, PSA 98.32, QED 0.74
Compound (SMILES): O=C(O)CN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: OLTATYQTWVJLBW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 428.44, ALogP 3.03, HBA 4, HBD 3, PSA 98.32, QED 0.56
Compound (SMILES): O=C(O)CN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(Cl)c4Cl)cc23)CC1
InChIKey: HAPYWJJHQALMFO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 461.35, ALogP 4.06, HBA 4, HBD 3, PSA 98.32, QED 0.51
Compound (SMILES): COc1cncc(-c2ccc3[nH]nc(C(=O)NCC4CCN(CC(=O)O)CC4)c3c2)c1
InChIKey: LCYDHOUWGGYAFJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 423.47, ALogP 2.16, HBA 6, HBD 3, PSA 120.44, QED 0.53
Compound (SMILES): CC1=NN(c2ccc(C(=O)O)cc2)C(=O)/C1=C/c1ccc(-c2cc(C)c(C)cc2[N+](=O)[O-])o1
InChIKey: HEKJYZZSCQBJGB-XDHOZWIPSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of p300 (unknown origin) using H3 peptide and acetyl-coA as substrate by fluorometric assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 445.43, ALogP 4.98, HBA 6, HBD 1, PSA 126.25, QED 0.34
Compound (SMILES): CN(C)CCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: TTZAIJYOUAIUID-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 84200 nM (pChEMBL 4.079999923706055)
Descriptors: MW 321.42, ALogP 3.5, HBA 4, HBD 1, PSA 51.38, QED 0.75
Compound (SMILES): CNCCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: IHPWSPZSFKTYCX-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 307.4, ALogP 3.16, HBA 4, HBD 2, PSA 60.17, QED 0.73
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 10300 nM (pChEMBL 4.989999771118164)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CNCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: QFZGTQOWVVISDX-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of recombinant human full-length nNOS expressed in Escherichia coli BL21(DE3) assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of calmodulin/10 uM H4B by hemoglobin capture assay
Measurement: Ki = 911 nM (pChEMBL 6.039999961853027)
Descriptors: MW 293.37, ALogP 3.12, HBA 4, HBD 2, PSA 60.17, QED 0.76
Compound (SMILES): NCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: ADYDYORVGGQJTJ-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 4830 nM (pChEMBL 5.320000171661377)
Descriptors: MW 279.34, ALogP 2.85, HBA 4, HBD 2, PSA 74.16, QED 0.77
Compound (SMILES): Nc1ccc2ccc(COc3cccnc3)cc2n1
InChIKey: QJTDCQJZJFACPC-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 5150 nM (pChEMBL 5.289999961853027)
Descriptors: MW 251.29, ALogP 2.79, HBA 4, HBD 1, PSA 61.03, QED 0.78
Compound (SMILES): CN(C)c1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: LSDVSQIABQLPIJ-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 293.37, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.8