lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CCCC5)ccn34)c12
InChIKey: DLURWSDCNVGXGS-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 = 193.5 nM (pChEMBL 6.710000038146973)
Descriptors: MW 526.65, ALogP 4.24, HBA 9, HBD 1, PSA 94.51, QED 0.29
Compound (SMILES): Cc1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OC6CCN(C)CC6)ccn45)cccc32)n1
InChIKey: RHDXUUDHWYWTHB-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 = 198.2 nM (pChEMBL 6.699999809265137)
Descriptors: MW 535.65, ALogP 5.04, HBA 8, HBD 1, PSA 89.58, QED 0.31
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CC[C@H](F)C5)ccn34)c12
InChIKey: WROWUZJYTYKDLR-NRFANRHFSA-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 = 219.3 nM (pChEMBL 6.659999847412109)
Descriptors: MW 541.63, ALogP 4.67, HBA 8, HBD 1, PSA 89.58, QED 0.29
Compound (SMILES): Cc1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCS(=O)(=O)CC6)ccn45)cccc32)n1
InChIKey: ILXAUJNLBADWCC-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 = 238.7 nM (pChEMBL 6.619999885559082)
Descriptors: MW 599.72, ALogP 3.67, HBA 10, HBD 1, PSA 123.72, QED 0.27
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(OC5CCN(C)CC5)ccn34)c12
InChIKey: SNVCSOILDYSSCA-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 = 267.7 nM (pChEMBL 6.570000171661377)
Descriptors: MW 526.65, ALogP 4.24, HBA 9, HBD 1, PSA 94.51, QED 0.33
Compound (SMILES): Cc1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CC7CCC(C6)O7)ccn45)cccc32)n1
InChIKey: DVLRGNOMLVHMMA-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 = 271.3 nM (pChEMBL 6.570000171661377)
Descriptors: MW 577.69, ALogP 4.81, HBA 9, HBD 1, PSA 98.81, QED 0.27
Compound (SMILES): Cn1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCCC6)ccn45)cccc32)c1=O
InChIKey: LPKSFIGZTYXYFQ-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 = 497.2 nM (pChEMBL 6.300000190734863)
Descriptors: MW 551.65, ALogP 4.04, HBA 9, HBD 1, PSA 98.69, QED 0.3
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CCOCC5)ccn34)c12
InChIKey: VYAWSTQXFZRJEY-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 = 325.9 nM (pChEMBL 6.489999771118164)
Descriptors: MW 542.64, ALogP 3.47, HBA 10, HBD 1, PSA 103.74, QED 0.29
Compound (SMILES): Cn1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCOCC6)ccn45)cccc32)c1=O
InChIKey: HTSMKADASCFLOB-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 = 558.4 nM (pChEMBL 6.25)
Descriptors: MW 567.65, ALogP 3.27, HBA 10, HBD 1, PSA 107.92, QED 0.29
Compound (SMILES): Cn1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCC6)ccn45)cccc32)c1=O
InChIKey: SQYKGTPWRZMMIK-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 = 703.3 nM (pChEMBL 6.150000095367432)
Descriptors: MW 537.62, ALogP 3.65, HBA 9, HBD 1, PSA 98.69, QED 0.31
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CCNCC5)ccn34)c12
InChIKey: VIIPUMFRADEZHH-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 = 276.2 nM (pChEMBL 6.559999942779541)
Descriptors: MW 538.66, ALogP 3.53, HBA 9, HBD 2, PSA 101.61, QED 0.3
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCCO)ccn34)c12
InChIKey: DPFMSWIHNGFWRO-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 = 192.4 nM (pChEMBL 6.71999979019165)
Descriptors: MW 470.53, ALogP 3.62, HBA 8, HBD 2, PSA 106.57, QED 0.36
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCC(F)(F)CN)ccn34)c12
InChIKey: CFIIFDUJSFTZCM-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 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 519.56, ALogP 4.22, HBA 8, HBD 2, PSA 112.36, QED 0.3
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OC5CNC5)ccn34)c12
InChIKey: KKFRWLUQPBFUNW-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 = 187.4 nM (pChEMBL 6.730000019073486)
Descriptors: MW 481.56, ALogP 3.6, HBA 8, HBD 2, PSA 98.37, QED 0.37
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCC5CNCCO5)ccn34)c12
InChIKey: BUAIQVYIPDXNCJ-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 = 141.2 nM (pChEMBL 6.849999904632568)
Descriptors: MW 525.61, ALogP 3.62, HBA 9, HBD 2, PSA 107.6, QED 0.32
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CC[C@@H](F)C5)ccn34)c12
InChIKey: WROWUZJYTYKDLR-OAQYLSRUSA-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 = 371.1 nM (pChEMBL 6.429999828338623)
Descriptors: MW 541.63, ALogP 4.67, HBA 8, HBD 1, PSA 89.58, QED 0.29
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCNCC5)ccn34)c12
InChIKey: SPLHYZQGBUXFFW-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 = 87.9 nM (pChEMBL 7.059999942779541)
Descriptors: MW 494.6, ALogP 3.66, HBA 8, HBD 2, PSA 92.38, QED 0.37
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCOCC5)ccn34)c12
InChIKey: CRXRSSSMXFMZGM-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 = 96.6 nM (pChEMBL 7.010000228881836)
Descriptors: MW 495.59, ALogP 4.09, HBA 8, HBD 1, PSA 89.58, QED 0.38
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CC[C@@H](O)C5)ccn34)c12
InChIKey: JLPRCUMPUUFCRL-OAQYLSRUSA-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 = 184.6 nM (pChEMBL 6.730000019073486)
Descriptors: MW 495.59, ALogP 3.82, HBA 8, HBD 2, PSA 100.58, QED 0.37
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCN(CCO)CC5)ccn34)c12
InChIKey: JFZVFMNLQNNQOS-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 = 152.3 nM (pChEMBL 6.820000171661377)
Descriptors: MW 538.66, ALogP 3.36, HBA 9, HBD 2, PSA 103.82, QED 0.31
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCC(O)CC5)ccn34)c12
InChIKey: JECFKXHCJNCOSD-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 = 170.5 nM (pChEMBL 6.769999980926514)
Descriptors: MW 509.61, ALogP 4.21, HBA 8, HBD 2, PSA 100.58, QED 0.36
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CC[C@H](O)C5)ccn34)c12
InChIKey: JLPRCUMPUUFCRL-NRFANRHFSA-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 = 218.7 nM (pChEMBL 6.659999847412109)
Descriptors: MW 495.59, ALogP 3.82, HBA 8, HBD 2, PSA 100.58, QED 0.37
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCN(CC)CC5)ccn34)c12
InChIKey: MJHDJRGWGGAQRJ-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 = 91.4 nM (pChEMBL 7.039999961853027)
Descriptors: MW 522.66, ALogP 4.39, HBA 8, HBD 1, PSA 83.59, QED 0.34
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCNC(=O)C5)ccn34)c12
InChIKey: FUHLOTZJQWQYRJ-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 = 204.9 nM (pChEMBL 6.690000057220459)
Descriptors: MW 508.59, ALogP 3.19, HBA 8, HBD 2, PSA 109.45, QED 0.36
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(N5CCCNCC5)ccn34)c12
InChIKey: NIKIYEZYAGVZBN-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 = 173.7 nM (pChEMBL 6.760000228881836)
Descriptors: MW 508.63, ALogP 4.05, HBA 8, HBD 2, PSA 92.38, QED 0.36
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(F)ccn34)c12
InChIKey: SPIPWDGHGPNYDD-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 = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 431.48, ALogP 3.9, HBA 7, HBD 1, PSA 82.04, QED 0.44
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(-n5cncn5)ccn34)c12
InChIKey: AEJSXLHXQILYJV-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 = 235.8 nM (pChEMBL 6.630000114440918)
Descriptors: MW 477.53, ALogP 3.83, HBA 9, HBD 1, PSA 107.82, QED 0.39
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(-n5cnc(C)n5)ccn34)c12
InChIKey: LWUFSZFCFWDIQR-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 = 232.2 nM (pChEMBL 6.630000114440918)
Descriptors: MW 491.56, ALogP 4.14, HBA 9, HBD 1, PSA 107.82, QED 0.38
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(-n5ncnc5C)ccn34)c12
InChIKey: VAIBMKQWAFGBFT-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 = 522.6 nM (pChEMBL 6.28000020980835)
Descriptors: MW 491.56, ALogP 4.14, HBA 9, HBD 1, PSA 107.82, QED 0.38
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(-n5cnnc5C)ccn34)c12
InChIKey: HWZZKJJFUJOUJT-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 = 929.2 nM (pChEMBL 6.03000020980835)
Descriptors: MW 491.56, ALogP 4.14, HBA 9, HBD 1, PSA 107.82, QED 0.38
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(OCC(O)CO)ccn34)c12
InChIKey: GGGKCVZNBSKLMB-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 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 500.56, ALogP 2.98, HBA 9, HBD 3, PSA 126.8, QED 0.28
Compound (SMILES): CCc1nn(Cc2ccn(CC)n2)c2cccc(NC(=O)c3cnc4cc(-c5cnn(C)c5)ccn34)c12
InChIKey: LBXXOGDHNJALPH-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 = 72.8 nM (pChEMBL 7.139999866485596)
Descriptors: MW 493.58, ALogP 4.16, HBA 9, HBD 1, PSA 99.86, QED 0.36
Compound (SMILES): CCc1nn(Cc2cc(C)n(C)n2)c2cccc(NC(=O)c3cnc4cc(-c5cnn(C)c5)ccn34)c12
InChIKey: HTBFXUDNRNBSSS-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 = 155.8 nM (pChEMBL 6.809999942779541)
Descriptors: MW 493.58, ALogP 3.99, HBA 9, HBD 1, PSA 99.86, QED 0.38
Compound (SMILES): CCc1nn(Cc2cc(C)n(C)n2)c2cccc(NC(=O)c3cnc4cc(-c5ccc(CN(C)C)o5)ccn34)c12
InChIKey: HUKITRXOTUDTJK-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 = 141.1 nM (pChEMBL 6.849999904632568)
Descriptors: MW 536.64, ALogP 4.91, HBA 9, HBD 1, PSA 98.42, QED 0.3
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(CCN5CC[C@@H](F)C5)ccn34)c12
InChIKey: KJFYFACFBMEHGE-JOCHJYFZSA-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 = 278.4 nM (pChEMBL 6.550000190734863)
Descriptors: MW 525.63, ALogP 4.84, HBA 7, HBD 1, PSA 80.35, QED 0.31
Compound (SMILES): CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(CCN5CCN(C)CC5)ccn34)c12
InChIKey: DOTOQJJAWOWHQF-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 = 157.4 nM (pChEMBL 6.800000190734863)
Descriptors: MW 536.68, ALogP 4.04, HBA 8, HBD 1, PSA 83.59, QED 0.32