lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cl.Clc1ccc(N2CCN(CCCCNc3noc(-c4ccccc4)n3)CC2)cc1
InChIKey: IPLCAXSRUDGODP-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-sulpiride from human dopamine D2 receptor expressed in HEK293 cells after 150 mins by liquid scintillation counting
Measurement: Ki = 79630 nM (pChEMBL 4.099999904632568)
Descriptors: MW 411.94, ALogP 4.4, HBA 6, HBD 1, PSA 57.43, QED 0.55
Compound (SMILES): O=C(O)C(=O)O.c1ccc(OCCNC[C@H]2COC(c3ccccc3)(c3ccccc3)O2)cc1
InChIKey: JAHHZJFOTROQSY-BQAIUKQQSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Displacement of [3H]prazosin from human recombinant alpha1B adrenoceptor expressed in CHO cell membrane after 30 mins by liquid scintillation counting
Measurement: Ki = 114.82 nM (pChEMBL 6.940000057220459)
Descriptors: MW 375.47, ALogP 3.97, HBA 4, HBD 1, PSA 39.72, QED 0.6
Compound (SMILES): O=C(O)C(=O)O.c1ccc(OCCNC[C@@H]2COC(c3ccccc3)(c3ccccc3)O2)cc1
InChIKey: JAHHZJFOTROQSY-GNAFDRTKSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Displacement of [3H]prazosin from human recombinant alpha1B adrenoceptor expressed in CHO cell membrane after 30 mins by liquid scintillation counting
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 375.47, ALogP 3.97, HBA 4, HBD 1, PSA 39.72, QED 0.6
Compound (SMILES): COc1cccc(OC)c1OCCNC[C@@H]1COc2ccccc2O1.O=C(O)C(=O)O
InChIKey: LBUNMGJPWDKBFD-PFEQFJNWSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Displacement of [3H]prazosin from human recombinant alpha1B adrenoceptor expressed in CHO cell membrane after 30 mins by liquid scintillation counting
Measurement: Ki = 72.44 nM (pChEMBL 7.139999866485596)
Descriptors: MW 345.4, ALogP 2.51, HBA 6, HBD 1, PSA 58.18, QED 0.74
Compound (SMILES): COc1cccc(OC)c1OCCNC[C@H]1COc2ccccc2O1.O=C(O)C(=O)O
InChIKey: LBUNMGJPWDKBFD-UQKRIMTDSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Displacement of [3H]prazosin from human recombinant alpha1B adrenoceptor expressed in CHO cell membrane after 30 mins by liquid scintillation counting
Measurement: Ki = 5.754 nM (pChEMBL 8.239999771118164)
Descriptors: MW 345.4, ALogP 2.51, HBA 6, HBD 1, PSA 58.18, QED 0.74
Compound (SMILES): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase L180M/M204V double mutant expressing telbivudine-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in secreted DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC(=O)c1nn(-c2ccccc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: GYXVNTAYSSWZCJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 4670 nM (pChEMBL 5.329999923706055)
Descriptors: MW 445.52, ALogP 6.28, HBA 4, HBD 1, PSA 67.75, QED 0.31
Compound (SMILES): CC(=O)c1nn(-c2ccc(C)cc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: OFQHAXNPHZJUNM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 9190 nM (pChEMBL 5.039999961853027)
Descriptors: MW 459.55, ALogP 6.58, HBA 4, HBD 1, PSA 67.75, QED 0.29
Compound (SMILES): CC(=O)c1nn(-c2ccc(Cl)cc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: KVFDSGCJLHAQKA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 4480 nM (pChEMBL 5.349999904632568)
Descriptors: MW 479.97, ALogP 6.93, HBA 4, HBD 1, PSA 67.75, QED 0.27
Compound (SMILES): CCOC(=O)c1nn(-c2ccccc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: UNKAGCJIUDPJFD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 3220 nM (pChEMBL 5.489999771118164)
Descriptors: MW 475.55, ALogP 6.25, HBA 5, HBD 1, PSA 76.98, QED 0.22
Compound (SMILES): CCOC(=O)c1nn(-c2ccc(C)cc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: QOWXYGQKYJHGRZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 7880 nM (pChEMBL 5.099999904632568)
Descriptors: MW 489.58, ALogP 6.56, HBA 5, HBD 1, PSA 76.98, QED 0.21
Compound (SMILES): CCOC(=O)c1nn(-c2ccc(Cl)cc2)cc1C(=O)c1c(C)[nH]c(-c2ccccc2)c1-c1ccccc1
InChIKey: YHOYTBGFZDFOAI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 509.99, ALogP 6.9, HBA 5, HBD 1, PSA 76.98, QED 0.19
Compound (SMILES): Cc1[nH]c(-c2ccccc2)c(-c2ccccc2)c1C(=O)c1cn(-c2ccccc2)nc1C(=O)Nc1ccccc1
InChIKey: JJCCJOXLGQVFLN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 3560 nM (pChEMBL 5.449999809265137)
Descriptors: MW 522.61, ALogP 7.33, HBA 4, HBD 2, PSA 79.78, QED 0.22
Compound (SMILES): Cc1ccc(-n2cc(C(=O)c3c(C)[nH]c(-c4ccccc4)c3-c3ccccc3)c(C(=O)Nc3ccccc3)n2)cc1
InChIKey: VQCXKJKPMSUSQU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 4490 nM (pChEMBL 5.349999904632568)
Descriptors: MW 536.64, ALogP 7.63, HBA 4, HBD 2, PSA 79.78, QED 0.21
Compound (SMILES): Cc1[nH]c(-c2ccccc2)c(-c2ccccc2)c1C(=O)c1cn(-c2ccc(Cl)cc2)nc1C(=O)Nc1ccccc1
InChIKey: PRSAJUGSNSUBMQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 3780 nM (pChEMBL 5.420000076293945)
Descriptors: MW 557.05, ALogP 7.98, HBA 4, HBD 2, PSA 79.78, QED 0.2
Compound (SMILES): Cc1[nH]c(-c2ccccc2)c(-c2ccccc2)c1C(=O)c1cn(-c2ccccc2)nc1-c1ccccc1
InChIKey: DURPLVDCJXSJNC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by microfluidic assay relative to control
Measurement: IC50 = 2560 nM (pChEMBL 5.590000152587891)
Descriptors: MW 479.58, ALogP 7.74, HBA 3, HBD 1, PSA 50.68, QED 0.25
Compound (SMILES): O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCC(CN2CCC(c3noc4cc(F)ccc34)CC2)CC1
InChIKey: LIHYUCWMNKTEOX-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19020
Assay: Displacement of [3H]7-OH-DPAT from dopamine D3 receptor in rat olfactory tubercle
Measurement: Ki = 236.8 nM (pChEMBL 6.630000114440918)
Descriptors: MW 525.57, ALogP 5.27, HBA 5, HBD 0, PSA 66.65, QED 0.43
Compound (SMILES): O=[N+]([O-])c1ccc(S(=O)(=O)N2CCC(CN3CCC(c4noc5cc(F)ccc45)CC3)CC2)cc1
InChIKey: RTIUOKVMNZFXBZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19020
Assay: Displacement of [3H]7-OH-DPAT from dopamine D3 receptor in rat olfactory tubercle
Measurement: Ki = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 502.57, ALogP 4.16, HBA 7, HBD 0, PSA 109.79, QED 0.37
Compound (SMILES): O=[N+]([O-])c1ccccc1S(=O)(=O)N1CCC(CN2CCC(c3noc4cc(F)ccc34)CC2)CC1
InChIKey: ROSOQGNSHDTFEN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from 5HT2A receptor in rat brain cortex
Measurement: Ki = 26.9 nM (pChEMBL 7.570000171661377)
Descriptors: MW 502.57, ALogP 4.16, HBA 7, HBD 0, PSA 109.79, QED 0.37
Compound (SMILES): O=[N+]([O-])c1cccc(S(=O)(=O)N2CCC(CN3CCC(c4noc5cc(F)ccc45)CC3)CC2)c1
InChIKey: NMXHWSGOIHHSLD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from 5HT2A receptor in rat brain cortex
Measurement: Ki = 135.2 nM (pChEMBL 6.869999885559082)
Descriptors: MW 502.57, ALogP 4.16, HBA 7, HBD 0, PSA 109.79, QED 0.37
Compound (SMILES): CCc1cc2c(cc1C1=CCN(C(=O)C3CCOCC3)CC1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: BTNPTMBSLGUHRO-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK expressed in human NCI-H3122 cells assessed as cell growth inhibition after 72 hrs by SRB/CCK-8 assay
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 507.63, ALogP 5.51, HBA 4, HBD 1, PSA 86.19, QED 0.51
Compound (SMILES): CCc1cc2c(cc1C1=CCN(CC3CCOCC3)CC1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: HVVDUMVMNROVAL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK expressed in human NCI-H3122 cells assessed as cell growth inhibition after 72 hrs by SRB/CCK-8 assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 493.65, ALogP 5.99, HBA 4, HBD 1, PSA 69.12, QED 0.48
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal His6-tagged recombinant human c-Met (974 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4(O)CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: GQCZYWQBXDXVLF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 12250 nM (pChEMBL 4.9120001792907715)
Descriptors: MW 483.61, ALogP 4.63, HBA 5, HBD 2, PSA 89.35, QED 0.57
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCOCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: ZOUKGWPEJXISGG-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 464.57, ALogP 5.69, HBA 5, HBD 1, PSA 83.7, QED 0.42
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCNCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: AGEWKUQZNAGGEC-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 463.59, ALogP 5.26, HBA 5, HBD 2, PSA 86.5, QED 0.43
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): C[C@@H](Oc1cc(-c2ccn(C3CCNCC3)n2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: CCASRZWPCOLUMW-GFCCVEGCSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin)
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 450.35, ALogP 5.04, HBA 6, HBD 2, PSA 77.99, QED 0.53
Compound (SMILES): COc1cccc(-c2nc3ccc(N4CCN(C)CC4)nn3c2-c2ccncc2)c1
InChIKey: PGJNVECBMPJQRU-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 400.49, ALogP 3.22, HBA 7, HBD 0, PSA 58.79, QED 0.52
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5c4OCO5)c(-c4ccncc4)n3n2)CC1
InChIKey: ZDPFVYBULQUGBM-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 414.47, ALogP 2.94, HBA 8, HBD 0, PSA 68.02, QED 0.51
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc5c(c4)OCO5)c(-c4ccncc4)n3n2)CC1
InChIKey: YIIPWHGYGYYCFZ-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 414.47, ALogP 2.94, HBA 8, HBD 0, PSA 68.02, QED 0.51
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5c4OCCO5)c(-c4ccncc4)n3n2)CC1
InChIKey: KWLALUJSWZSEHQ-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 428.5, ALogP 2.98, HBA 8, HBD 0, PSA 68.02, QED 0.5
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc5c(c4)OCCO5)c(-c4ccncc4)n3n2)CC1
InChIKey: HLPMOIBLQACUJJ-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 428.5, ALogP 2.98, HBA 8, HBD 0, PSA 68.02, QED 0.5
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc5ncsc5c4)c(-c4ccncc4)n3n2)CC1
InChIKey: SSGUNNUGCYUWCP-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 427.54, ALogP 3.82, HBA 8, HBD 0, PSA 62.45, QED 0.44
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc5ccccc45)c(-c4ccncc4)n3n2)CC1
InChIKey: RTWXJPNBTHXJKE-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 420.52, ALogP 4.36, HBA 6, HBD 0, PSA 49.56, QED 0.43
Compound (SMILES): COc1ccc2c(-c3nc4ccc(N5CCN(C)CC5)nn4c3-c3ccncc3)cccc2c1
InChIKey: KIRLMHCLAUXGKI-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 450.55, ALogP 4.37, HBA 7, HBD 0, PSA 58.79, QED 0.41
Compound (SMILES): CCOc1ccc2c(-c3nc4ccc(N5CCN(C)CC5)nn4c3-c3ccncc3)cccc2c1
InChIKey: RVTKFEDCJXYAJV-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 464.57, ALogP 4.76, HBA 7, HBD 0, PSA 58.79, QED 0.37
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc(-c5ccccc5)cc4)c(-c4ccncc4)n3n2)CC1
InChIKey: MVDDEMQPGZMNOI-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 446.56, ALogP 4.88, HBA 6, HBD 0, PSA 49.56, QED 0.39
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc(-c5ccccc5)c4)c(-c4ccncc4)n3n2)CC1
InChIKey: BFGWDKKQMJFYGX-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 446.56, ALogP 4.88, HBA 6, HBD 0, PSA 49.56, QED 0.39
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc(-c5cccs5)c4)c(-c4ccncc4)n3n2)CC1
InChIKey: OGBWSKFFKIHDAT-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 452.59, ALogP 4.94, HBA 7, HBD 0, PSA 49.56, QED 0.39
Compound (SMILES): CN1CCN(c2ccc3nc(-c4cccc(-c5ccsc5)c4)c(-c4ccncc4)n3n2)CC1
InChIKey: SFRAFCXSYLFFIR-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 452.59, ALogP 4.94, HBA 7, HBD 0, PSA 49.56, QED 0.39
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc(-c5ccccc5)s4)c(-c4ccncc4)n3n2)CC1
InChIKey: VEKOIBRRCRBMOR-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Inhibition of full length human GST-tagged RIPK3 expressed in Spodoptera frugiperda Sf9 cells after 30 mins by scintillation and luminescence counting method in the presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 452.59, ALogP 4.94, HBA 7, HBD 0, PSA 49.56, QED 0.39
Compound (SMILES): CN1CCN(c2ccc3nc(-c4ccc(C(=O)N5CCOCC5)cc4)c(-c4ccncc4)n3n2)CC1
InChIKey: PTFDQIBTFLXUAW-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Inhibition of full length human GST-tagged RIPK3 expressed in Spodoptera frugiperda Sf9 cells 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: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Inhibition of full length human GST-tagged RIPK3 expressed in Spodoptera frugiperda Sf9 cells 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(-c4cccc5c4OCO5)c(-c4cccnc4)n3n2)CC1
InChIKey: JXSPMVJUQGQTOQ-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 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: 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 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: 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 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: 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 413.48, ALogP 3.54, HBA 7, HBD 0, PSA 55.13, QED 0.51
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 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 408.5, ALogP 2.96, HBA 5, HBD 3, PSA 90.48, 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: Competitive inhibition of human recombinant GSK-3beta after 60 mins by microfluidic assay in presence of ATP
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
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(-c4cncc(OC)c4)cc23)CC1
InChIKey: CSEMNQRANZNKJH-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 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: 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): 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: 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 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: 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 = 10 nM (pChEMBL 8)
Descriptors: MW 495.49, ALogP 3.84, HBA 6, HBD 3, PSA 124.35, QED 0.36
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 VMA intein chitin binding domain-fused p300 HAT domain (1287 to 1652 residues) (unknown origin) expressed in Escherichia coli BL21(RIL)-DE3 using H4-15 and acetyl-coA as substrate preincubated for 10 mins followed by substrate addition in presence of NAD by alpha-ketoglutarate dehydrogenase enzyme coupled spectrophotometric assay
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
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 = 216 nM (pChEMBL 6.670000076293945)
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), Mus musculus
UniProt: Q9Z0J4
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 = 12500 nM (pChEMBL 4.900000095367432)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
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 = 21 nM (pChEMBL 7.679999828338623)
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, inducible (SINGLE PROTEIN), Mus musculus
UniProt: P29477
Assay: Inhibition of recombinant mouse macrophage iNOS expressed in Escherichia coli assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of 10 uM H4B by hemoglobin capture assay
Measurement: Ki = 33200 nM (pChEMBL 4.480000019073486)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
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 = 25 nM (pChEMBL 7.599999904632568)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
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 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), Mus musculus
UniProt: Q9Z0J4
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 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 293.37, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.8
Compound (SMILES): CN(C)CCCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: OVBOFIXDCJHRLP-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
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 = 40500 nM (pChEMBL 4.389999866485596)
Descriptors: MW 335.45, ALogP 3.89, HBA 4, HBD 1, PSA 51.38, QED 0.71
Compound (SMILES): CN(C)CCOc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: XRNGQGQMDXUBOX-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
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 = 7440 nM (pChEMBL 5.130000114440918)
Descriptors: MW 337.42, ALogP 3.34, HBA 5, HBD 1, PSA 60.61, QED 0.72
Compound (SMILES): CN(C)Cc1cccc(NCc2ccc3ccc(N)nc3c2)c1
InChIKey: KLVQNBMBSWDRJZ-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
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 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 306.41, ALogP 3.49, HBA 4, HBD 2, PSA 54.18, QED 0.76