lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCSc1cc(-n2[nH]cc(-n3ccnn3)c2=O)ncn1
InChIKey: SOKNGTGXLCNVNA-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition Assay: Hydroxylated HIF bonds specifically to the von Hippel-Lindau protein-elongin B-elongin C complex (VBC complex). This interaction occurs only if HIF is hydroxylated on a conserved prolyl radical. It is the basis for the biochemical determination of HIF prolyl hydroxylase activity. The test is carried out as described [Oehme F., Jonghaus W., Narouz-Ott L., Huetter J., Flamme I., Anal. Biochem. 330 (1), 74-80 (2004)].
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 289.32, ALogP 0.65, HBA 8, HBD 1, PSA 94.28, QED 0.56
Compound (SMILES): O=c1c(-n2ccnn2)c[nH]n1-c1cc(N2CCSCC2)ncn1
InChIKey: RNUYQJMMQZQPJZ-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition Assay: Hydroxylated HIF bonds specifically to the von Hippel-Lindau protein-elongin B-elongin C complex (VBC complex). This interaction occurs only if HIF is hydroxylated on a conserved prolyl radical. It is the basis for the biochemical determination of HIF prolyl hydroxylase activity. The test is carried out as described [Oehme F., Jonghaus W., Narouz-Ott L., Huetter J., Flamme I., Anal. Biochem. 330 (1), 74-80 (2004)].
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 330.38, ALogP 0.09, HBA 9, HBD 1, PSA 97.52, QED 0.73
Compound (SMILES): CC1CCN(c2cc(-n3[nH]cc(-n4ccnn4)c3=O)ncn2)CC1
InChIKey: RKCNYWUNTZBUJJ-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition Assay: Hydroxylated HIF bonds specifically to the von Hippel-Lindau protein-elongin B-elongin C complex (VBC complex). This interaction occurs only if HIF is hydroxylated on a conserved prolyl radical. It is the basis for the biochemical determination of HIF prolyl hydroxylase activity. The test is carried out as described [Oehme F., Jonghaus W., Narouz-Ott L., Huetter J., Flamme I., Anal. Biochem. 330 (1), 74-80 (2004)].
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 326.36, ALogP 0.77, HBA 8, HBD 1, PSA 97.52, QED 0.76
Compound (SMILES): COC1CCCN(c2cc(-n3[nH]cc(-n4ccnc4)c3=O)ncn2)C1
InChIKey: QAYFFINJEBFRDQ-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition Assay: Hydroxylated HIF bonds specifically to the von Hippel-Lindau protein-elongin B-elongin C complex (VBC complex). This interaction occurs only if HIF is hydroxylated on a conserved prolyl radical. It is the basis for the biochemical determination of HIF prolyl hydroxylase activity. The test is carried out as described [Oehme F., Jonghaus W., Narouz-Ott L., Huetter J., Flamme I., Anal. Biochem. 330 (1), 74-80 (2004)].
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 341.38, ALogP 0.76, HBA 8, HBD 1, PSA 93.86, QED 0.75
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2ccn(-c3ccccc3F)n2)CC1)c1cccc(F)n1
InChIKey: MQIKJQQQDIIXLP-GASCZTMLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 425.44, ALogP 3.47, HBA 5, HBD 2, PSA 88.91, QED 0.61
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2ccn(-c3ccccc3F)n2)CC1)c1cccc(Cl)n1
InChIKey: KLEYVDWXPKPAEX-GASCZTMLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 441.89, ALogP 3.99, HBA 5, HBD 2, PSA 88.91, QED 0.59
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2cccc(-c3ccccc3F)c2)CC1)c1ccccc1
InChIKey: LTWJKLJPPJDNGM-TYKWCNGQSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 416.5, ALogP 5.42, HBA 2, HBD 2, PSA 58.2, QED 0.58
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](NC(=O)c4ccccc4)CC3)ccc21
InChIKey: XTYOJYXLFHVAHM-HDICACEKSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 421.5, ALogP 4.1, HBA 5, HBD 2, PSA 93.34, QED 0.65
Compound (SMILES): N#Cc1ccccc1C(=O)N[C@H]1CC[C@@H](C(=O)Nc2ccn(-c3ccccc3F)n2)CC1
InChIKey: UVECXRMWVIOMGL-MAEOIBBWSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 431.47, ALogP 3.81, HBA 5, HBD 2, PSA 99.81, QED 0.64
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2cccc(-c3ccccc3F)c2)CC1)c1ccon1
InChIKey: CORJZZNGLVYDPC-WOVMCDHWSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 407.45, ALogP 4.41, HBA 4, HBD 2, PSA 84.23, QED 0.66
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2ccc(-c3ccccc3F)cc2)CC1)c1ccon1
InChIKey: PWWFFXGAOVSLKQ-MAEOIBBWSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 407.45, ALogP 4.41, HBA 4, HBD 2, PSA 84.23, QED 0.66
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](NC(=O)c4ccon4)CC3)ccc21
InChIKey: PPQMXAXIRZKXHE-OKILXGFUSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 412.45, ALogP 3.09, HBA 7, HBD 2, PSA 119.37, QED 0.66
Compound (SMILES): O=C(N[C@H]1CC[C@@H](C(=O)Nc2ccc(-c3ccccc3)cc2)CC1)c1ccon1
InChIKey: MNARXDIEJURKNW-PUZFROQSSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.65 nM (pChEMBL 9.1899995803833)
Descriptors: MW 389.46, ALogP 4.27, HBA 4, HBD 2, PSA 84.23, QED 0.68
Compound (SMILES): O=C(N[C@H]1CC[C@@H](c2nc(-c3ccc(Cl)c(Cl)c3)c[nH]2)CC1)c1ccon1
InChIKey: CWRPSMSLGXTWCU-BJHJDKERSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 405.29, ALogP 4.83, HBA 4, HBD 2, PSA 83.81, QED 0.65
Compound (SMILES): O=C(N[C@H]1CC[C@@H](c2nc(-c3cccc(Cl)c3)c[nH]2)CC1)c1ccon1
InChIKey: AFHJVERWEBAZJU-JNSHFYNHSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 370.84, ALogP 4.17, HBA 4, HBD 2, PSA 83.81, QED 0.72
Compound (SMILES): O=C(N[C@H]1CC[C@@H](c2nc(-c3cccc(C(F)(F)F)c3)c[nH]2)CC1)c1ccon1
InChIKey: SMFOKUWSWBHMFT-JNSHFYNHSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 404.39, ALogP 4.54, HBA 4, HBD 2, PSA 83.81, QED 0.67
Compound (SMILES): O=C(Nc1ccn(-c2ccccc2F)n1)[C@H]1CC[C@@H](Nc2cccc(F)n2)CC1
InChIKey: BTAFTIZFQLUJSL-GASCZTMLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 397.43, ALogP 4.15, HBA 5, HBD 2, PSA 71.84, QED 0.63
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](Nc4cccc(F)n4)CC3)ccc21
InChIKey: SBXHAOOYZCFMGG-GASCZTMLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 412.47, ALogP 4.32, HBA 6, HBD 2, PSA 89.16, QED 0.61
Compound (SMILES): C[C@@H]1CN(c2ccc(NC(=O)[C@H]3CC[C@@H](Oc4cc(Cl)ccn4)CC3)cc2)C[C@H](C)O1
InChIKey: CJAWKTONYJOHOK-XYGUIBQMSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 443.98, ALogP 4.92, HBA 5, HBD 1, PSA 63.69, QED 0.71
Compound (SMILES): N#Cc1ccccc1O[C@H]1CC[C@@H](C(=O)Nc2ccc(OC(F)F)cc2)CC1
InChIKey: UBNGXMOXMNDNQF-KDYLLFBJSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 386.4, ALogP 4.74, HBA 4, HBD 1, PSA 71.35, QED 0.78
Compound (SMILES): C[C@@H]1CN(c2ccc(NC(=O)[C@H]3CC[C@@H](Oc4cc(C(F)(F)F)ccc4C#N)CC3)cc2)C[C@H](C)O1
InChIKey: XFBXWXXATGSMIO-KSNQQSQUSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 501.55, ALogP 5.77, HBA 5, HBD 1, PSA 74.59, QED 0.56
Compound (SMILES): C[C@@H]1CN(c2ccc(NC(=O)[C@H]3CC[C@@H](Oc4cc(Cl)ccc4C#N)CC3)cc2)C[C@H](C)O1
InChIKey: MGIROGTULLABHB-KSNQQSQUSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 468, ALogP 5.4, HBA 5, HBD 1, PSA 74.59, QED 0.64
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](Oc4cc(Cl)ccc4C#N)CC3)ccc21
InChIKey: FIBBZHWCWNWZOF-GLRZTSSQSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 453.93, ALogP 5.28, HBA 6, HBD 1, PSA 97.26, QED 0.57
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](Oc4cc(C(F)(F)F)ccc4C#N)CC3)ccc21
InChIKey: ZPABSALHRDBLAL-GLRZTSSQSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.68 nM (pChEMBL 9.170000076293945)
Descriptors: MW 487.48, ALogP 5.64, HBA 6, HBD 1, PSA 97.26, QED 0.5
Compound (SMILES): CC(C)n1c(=O)oc2cc(NC(=O)[C@H]3CC[C@@H](Oc4cc(C(F)(F)F)ccn4)CC3)ccc21
InChIKey: NCWOHEXANIQJBB-KDYLLFBJSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 463.46, ALogP 5.17, HBA 6, HBD 1, PSA 86.36, QED 0.56
Compound (SMILES): O=C(Nc1ccn(-c2ccccc2F)n1)[C@H]1CC[C@@H](Oc2cc(Cl)ccn2)CC1
InChIKey: CNEBXWXMELJZFE-FZNQNYSPSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.69 nM (pChEMBL 9.15999984741211)
Descriptors: MW 414.87, ALogP 4.64, HBA 5, HBD 1, PSA 69.04, QED 0.66
Compound (SMILES): O=C(Nc1ccn(-c2ccccc2F)n1)[C@H]1CC[C@@H](N2c3ccccc3OS2(=O)=O)CC1
InChIKey: PLGNLXVIIQOAPK-IYBDPMFKSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Binding Assay: cDNA sequence encoding mouse NPY Y5 receptor (Biochem. Biophys. Acta 1328: 83-89, 1997) was cloned in the expression vector (pME18S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host according to the instruction manual using Lipofectamine reagent (Trademark, Gibco BRL Co., Ltd.). The cells that stably express NPY Y5 receptor were obtained.The membrane samples prepared from the CHO cells expressing NPY Y5 receptor, the compound of the invention and 30,000 cpm 125I peptide YY (60 pM of final concentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25° C. for 2 hours. The membrane samples were then filtered from the mixture through a glassfilter (GF/C) presoaked with 1% polyethyleneimine. After washing with 50 mM Tris-HCl buffer (pH 7.4), radioactivity retained on the filters was determined using gamma counter.
Measurement: IC50 = 0.58 nM (pChEMBL 9.239999771118164)
Descriptors: MW 456.5, ALogP 3.65, HBA 6, HBD 1, PSA 93.53, QED 0.65
Compound (SMILES): Fc1ccc2c(c1)C(N1CCNCC1)=Nc1ccccc1S2
InChIKey: CXKQSMUCGLKJEI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding Assay: The ability of test compounds to displace 3H-raclopride at the D2s receptor can be determined on membranes from D2s-transfected CHO cells (Bmax 13 pmol/mg protein). An assay can use a standard 96-well glass-fiber filter plate to retain radioligand bound by the receptor. Retained 3H can be determined in a TopCount scintillation plate counter following the addition of a liquid scintillant to each well. Compounds can be evaluated for their potency using competition curve analysis, resulting in calculated Ki values.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 313.4, ALogP 3.27, HBA 4, HBD 1, PSA 27.63, QED 0.81
Compound (SMILES): Clc1ccc2c(c1)C(N1CCNCC1)=Nc1ccccc1S2
InChIKey: NYXDYIWPZMXTPA-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding Assay: The ability of test compounds to displace 3H-raclopride at the D2s receptor can be determined on membranes from D2s-transfected CHO cells (Bmax 13 pmol/mg protein). An assay can use a standard 96-well glass-fiber filter plate to retain radioligand bound by the receptor. Retained 3H can be determined in a TopCount scintillation plate counter following the addition of a liquid scintillant to each well. Compounds can be evaluated for their potency using competition curve analysis, resulting in calculated Ki values.
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 329.86, ALogP 3.79, HBA 4, HBD 1, PSA 27.63, QED 0.8
Compound (SMILES): CN1CCN(C2=Nc3ccccc3Sc3ccc(F)cc32)CC1
InChIKey: GSYXWIMVZURMCS-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding Assay: The ability of test compounds to displace 3H-raclopride at the D2s receptor can be determined on membranes from D2s-transfected CHO cells (Bmax 13 pmol/mg protein). An assay can use a standard 96-well glass-fiber filter plate to retain radioligand bound by the receptor. Retained 3H can be determined in a TopCount scintillation plate counter following the addition of a liquid scintillant to each well. Compounds can be evaluated for their potency using competition curve analysis, resulting in calculated Ki values.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 327.43, ALogP 3.62, HBA 4, HBD 0, PSA 18.84, QED 0.74
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4c(F)cccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: BKAVUKDORGWRAO-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4ccccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: OMGMLXZAIWEESM-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 472.48, ALogP 2.35, HBA 8, HBD 0, PSA 83.28, QED 0.58
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4c(F)cccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: USSWCJBLIIGXQA-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4cc(F)ccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: DOPCTFLLQXBISR-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 447 nM (pChEMBL 6.349999904632568)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4ccccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: JCZKDUWJCWYWSC-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 434.5, ALogP 1.34, HBA 9, HBD 0, PSA 92.51, QED 0.59
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4ccc(F)cc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: UQVBWHBTBGUFNT-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4ccc(F)cc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: VBWSYPVWXJCAFJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4sccc4-n4cccc4)CC3C2)n1
InChIKey: DVFNTCCOGHJMNT-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 542 nM (pChEMBL 6.269999980926514)
Descriptors: MW 393.52, ALogP 3.15, HBA 6, HBD 0, PSA 54.26, QED 0.69
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4cc(F)ccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: IIGOHRICMDAQQK-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 101 nM (pChEMBL 7)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52