lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCC6)ccn45)cccc32)n1
InChIKey: QTMXTKJOEMDYEF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: LANCE Ultra TR-FRET Assay: The ability of compounds of Formula I to inhibit cFMS was determined by the following assay. cFMS enzymatic activity was measured using the LANCE Ultra TR-FRET assay technology from PerkinElmer (Waltham, Mass.). Incubation mixtures contained the following: 50 mM NaHEPES, pH 7.3, 10 mM MgCl2, 0.5 mM MnCl2, 0.01% Triton X-100, 1 mM DTT, 1% DMSO, 10 uM ATP, 25 nM LANCE Ultra ULight-poly GAT and 0.5 nM cFMS in a total volume of 10 uL. The concentration of compounds of Formula I was varied over 10-point, 3-fold dilution series with 10,000 nM typically being the highest dose. Incubations were carried out in white ProxyPlate-384 Plus plates (PerkinElmer) at 22 C. for 20 minutes, after which 10 uL of a quench/detection solution was added containing 1x LANCE Detection Buffer, 2 nM LANCE EuW1024 Anti-phosphotyrosine (PY20) and 36 mM EDTA. After an additional 60 minutes incubation at 22 C., the assay plate was read on an EnVision 2103 Multilabel Reader (PerkinElmer).
Measurement: IC50 = 149.8 nM (pChEMBL 6.820000171661377)
Descriptors: MW 521.63, ALogP 4.65, HBA 8, HBD 1, PSA 89.58, QED 0.3
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(-n5cncn5)ccn34)c12
InChIKey: JRCPYNSPYPUPII-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: LANCE Ultra TR-FRET Assay: The ability of compounds of Formula I to inhibit cFMS was determined by the following assay. cFMS enzymatic activity was measured using the LANCE Ultra TR-FRET assay technology from PerkinElmer (Waltham, Mass.). Incubation mixtures contained the following: 50 mM NaHEPES, pH 7.3, 10 mM MgCl2, 0.5 mM MnCl2, 0.01% Triton X-100, 1 mM DTT, 1% DMSO, 10 uM ATP, 25 nM LANCE Ultra ULight-poly GAT and 0.5 nM cFMS in a total volume of 10 uL. The concentration of compounds of Formula I was varied over 10-point, 3-fold dilution series with 10,000 nM typically being the highest dose. Incubations were carried out in white ProxyPlate-384 Plus plates (PerkinElmer) at 22 C. for 20 minutes, after which 10 uL of a quench/detection solution was added containing 1x LANCE Detection Buffer, 2 nM LANCE EuW1024 Anti-phosphotyrosine (PY20) and 36 mM EDTA. After an additional 60 minutes incubation at 22 C., the assay plate was read on an EnVision 2103 Multilabel Reader (PerkinElmer).
Measurement: IC50 = 462.7 nM (pChEMBL 6.329999923706055)
Descriptors: MW 480.54, ALogP 3.34, HBA 10, HBD 1, PSA 112.75, QED 0.38
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4ccccc4C3=O)nc3ncccc3c2=O)cc1
InChIKey: RNKUIMMOMHANNA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 426.43, ALogP 2.63, HBA 7, HBD 0, PSA 94.39, QED 0.46
Compound (SMILES): O=C1c2ccccc2C(=O)N1CCc1nc2ccccc2c(=O)n1-c1cccc(-c2ccccc2)c1
InChIKey: AWBBMMVEECJSGI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 471.52, ALogP 4.89, HBA 5, HBD 0, PSA 72.27, QED 0.34
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4ccccc4C3=O)nc3cc(Cl)ccc3c2=O)cc1
InChIKey: QBUULRABEGWKMS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 459.89, ALogP 3.89, HBA 6, HBD 0, PSA 81.5, QED 0.42
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4ccc(C)cc4C3=O)nc3ccccc3c2=O)cc1
InChIKey: FCUOAVYXMNOEBT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 439.47, ALogP 3.54, HBA 6, HBD 0, PSA 81.5, QED 0.44
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(C#N)c4C3=O)nc3ccccc3c2=O)cc1
InChIKey: MVVHNAYPICIVGV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 450.45, ALogP 3.1, HBA 7, HBD 0, PSA 105.29, QED 0.43
Compound (SMILES): COc1ccc2c(=O)n(-c3cccc(C)c3)c(CCN3C(=O)c4cccc(OC)c4C3=O)nc2c1
InChIKey: SAFUEMQHBOCBCP-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 469.5, ALogP 3.55, HBA 7, HBD 0, PSA 90.73, QED 0.4
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OC)c4C3=O)nc3cc(C)ccc3c2=O)cc1
InChIKey: DCTVCZMLANHMER-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 469.5, ALogP 3.55, HBA 7, HBD 0, PSA 90.73, QED 0.4
Compound (SMILES): COc1ccc(-n2c(CCc3cn(C(=O)OC(C)(C)C)c4ccccc34)nc3ccccc3c2=O)cc1
InChIKey: NMPJVADDKOQVEX-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 495.58, ALogP 5.92, HBA 7, HBD 0, PSA 75.35, QED 0.3
Compound (SMILES): COc1ccc(-n2c(CCNC(=O)Nc3ccccc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: FTPLXQQPNVAVID-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 490.56, ALogP 5.43, HBA 5, HBD 2, PSA 85.25, QED 0.32
Compound (SMILES): CC(C)Oc1cccc2c1C(=O)N(CCc1nc3ccccc3c(=O)n1-c1ccc(OCCF)cc1)C2=O
InChIKey: YLIKQOMAHCESOT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 515.54, ALogP 4.36, HBA 7, HBD 0, PSA 90.73, QED 0.31
Compound (SMILES): COc1ccc2c(=O)n(-c3ccc4cc[nH]c4c3)c(CCN3C(=O)c4cccc(OC(C)C)c4C3=O)nc2c1
InChIKey: QEVGHBFOXHSDPB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.055 nM (pChEMBL 10.260000228881836)
Descriptors: MW 522.56, ALogP 4.5, HBA 7, HBD 1, PSA 106.52, QED 0.32
Compound (SMILES): COc1ccc2c(=O)n(-c3cccc(C)c3)c(CCN3C(=O)c4cccc(OC(C)C)c4C3=O)nc2c1
InChIKey: MEVJDZAVRUDOGR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.077 nM (pChEMBL 10.109999656677246)
Descriptors: MW 497.55, ALogP 4.33, HBA 7, HBD 0, PSA 90.73, QED 0.35
Compound (SMILES): CC(C)Oc1cccc2c1C(=O)N(CCc1nc3ncccc3c(=O)n1-c1ccc3cn[nH]c3c1)C2=O
InChIKey: AKMCIBXGYWTFKF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 494.51, ALogP 3.28, HBA 8, HBD 1, PSA 123.07, QED 0.36
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OCC(F)(F)F)c4C3=O)nc3ccccc3c2=O)cc1
InChIKey: GZIXHCWJCRDAFZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 523.47, ALogP 4.17, HBA 7, HBD 0, PSA 90.73, QED 0.34
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OCC5CC5)c4C3=O)nc3ccccc3c2=O)cc1
InChIKey: ULMKMPLKFRBYMF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 495.54, ALogP 4.02, HBA 7, HBD 0, PSA 90.73, QED 0.34
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OC5CCC5)c4C3=O)nc3ccccc3c2=O)cc1
InChIKey: GRYSVNWSYASJCG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 495.54, ALogP 4.16, HBA 7, HBD 0, PSA 90.73, QED 0.36
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OCC(F)(F)F)c4C3=O)nc3nc(C)ccc3c2=O)cc1
InChIKey: VWOSCNVUZSGCPU-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 2.08 nM (pChEMBL 8.680000305175781)
Descriptors: MW 538.48, ALogP 3.88, HBA 8, HBD 0, PSA 103.62, QED 0.33
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(OC(C)C)c4C3=O)nc3cc(C)ccc3c2=O)cc1
InChIKey: ZCNRGLKRZFMMNC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 497.55, ALogP 4.33, HBA 7, HBD 0, PSA 90.73, QED 0.35
Compound (SMILES): CC(C)Oc1cccc2c1C(=O)N(CCc1nc3ccccc3c(=O)n1C1CCCCC1)C2=O
InChIKey: MENOKBUYEGKFEJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 459.55, ALogP 4.53, HBA 6, HBD 0, PSA 81.5, QED 0.51
Compound (SMILES): Cc1ccc2c(=O)n(-c3ccc4cn[nH]c4c3)c(CCN3C(=O)c4cccc(OC(C)C)c4C3=O)nc2c1
InChIKey: CNNZJEYBLDLUJS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 507.55, ALogP 4.2, HBA 7, HBD 1, PSA 110.18, QED 0.35
Compound (SMILES): Cc1ccc2c(=O)n(-c3ccc4cnn(C)c4c3)c(CCN3C(=O)c4cccc(OC(C)C)c4C3=O)nc2c1
InChIKey: RIWAAUCMKQVYIN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.024 nM (pChEMBL 10.619999885559082)
Descriptors: MW 521.58, ALogP 4.21, HBA 8, HBD 0, PSA 99.32, QED 0.31
Compound (SMILES): COc1ccc(-n2c(CCN3C(=O)c4cccc(-c5ncco5)c4C3=O)nc3ccccc3c2=O)cc1
InChIKey: YOFULGABLDXGKR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 492.49, ALogP 3.89, HBA 8, HBD 0, PSA 107.53, QED 0.33
Compound (SMILES): CC(C)Oc1cccc2c1C(=O)N(CCc1nc3ccccc3c(=O)n1-c1ccc(OCc3ccccc3)cc1)C2=O
InChIKey: QVZVCQURRYIEEL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 559.62, ALogP 5.59, HBA 7, HBD 0, PSA 90.73, QED 0.22
Compound (SMILES): CC(C)Oc1cccc2c1C(=O)N(CCc1nc3ccccc3c(=O)n1-c1ccc(O)cc1)C2=O
InChIKey: CZEAEMJFSYTBRT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 469.5, ALogP 3.72, HBA 7, HBD 1, PSA 101.73, QED 0.43
Compound (SMILES): COc1ccc(-n2c(CCNC(=O)c3ccccc3OC)nc3ccccc3c2=O)cc1
InChIKey: NFENKSRTQBOIQT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Florescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the Examples had activity in reference assays by exhibiting their ability to inhibit the hydrolysis of the phosphate ester bond of a cyclic nucleotide. Any compound exhibiting a Ki (inhibitory constant) below 1 uM would be considered a PDE10 inhibitor as defined herein.In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence.
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 429.48, ALogP 3.38, HBA 6, HBD 1, PSA 82.45, QED 0.49
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: MECRBBLUTQSQAP-ZLCORKTQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 1067.23
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: DHQKURVDSAVGBS-IJRTVYNZSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 873 nM (pChEMBL 6.059999942779541)
Descriptors: MW 1058.26
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CO)NC1=O
InChIKey: LSBWSLRGIMZZMW-SFGQYLDMSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 1446 nM (pChEMBL 5.840000152587891)
Descriptors: MW 1017.16
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CO)NC1=O
InChIKey: ZYOPHGZIHHZUOQ-QAOZGKSNSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 4293 nM (pChEMBL 5.369999885559082)
Descriptors: MW 989.15, ALogP -3.07, HBA 12, HBD 15, PSA 399.83, QED 0.04
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](C)NC1=O
InChIKey: WQOIVMOIKQDVGY-RLBQVKLDSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 2048 nM (pChEMBL 5.690000057220459)
Descriptors: MW 1002.15
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: GDFYJHXUWSIIOB-MFVUMRCOSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 533 nM (pChEMBL 6.269999980926514)
Descriptors: MW 1039.21
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: GSEHSXUIONCBGL-RZOXKKKKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 2957 nM (pChEMBL 5.53000020980835)
Descriptors: MW 1030.25
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](C)NC1=O
InChIKey: DYKSECBZOZHIRT-UWSLGBFJSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 3018 nM (pChEMBL 5.519999980926514)
Descriptors: MW 973.15, ALogP -2.05, HBA 11, HBD 14, PSA 379.6, QED 0.04