lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC1(c2ccc(-c3nc4c5cccc(Br)c5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: QEYYDDZOUTZDSR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 469.39, ALogP 6.32, HBA 4, HBD 1, PSA 56.21, QED 0.34
Compound (SMILES): NC1(c2ccc(-c3nc4c5cccc(-c6ccc(F)cc6)c5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: ZCPZAYQMFZTOEC-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 484.58, ALogP 7.36, HBA 4, HBD 1, PSA 56.21, QED 0.28
Compound (SMILES): NC1(c2ccc(-c3nc4c5cccc(-c6ccc(CO)cc6)c5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: FQWKNVNOFXOAJS-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 496.61, ALogP 6.71, HBA 5, HBD 2, PSA 76.44, QED 0.28
Compound (SMILES): CS(=O)(=O)c1cccc(-c2cccc3c2nn2cc(-c4ccccc4)c(-c4ccc(C5(N)CCC5)cc4)nc32)c1
InChIKey: RIIDZBPZGUCUOW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 544.68, ALogP 6.62, HBA 6, HBD 1, PSA 90.35, QED 0.26
Compound (SMILES): NC1(c2ccc(-c3nc4c5cccc(-c6cn[nH]c6)c5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: GMNRWIFWEPXNOP-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 456.55, ALogP 5.94, HBA 5, HBD 2, PSA 84.89, QED 0.34
Compound (SMILES): N#Cc1cccc2c1nn1cc(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc21
InChIKey: WPAFIZJKHVLCRP-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 415.5, ALogP 5.43, HBA 5, HBD 1, PSA 80, QED 0.43
Compound (SMILES): COC(=O)c1cccc2c1nn1cc(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc21
InChIKey: FZNVVBCJEGQFRR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 448.53, ALogP 5.34, HBA 6, HBD 1, PSA 82.51, QED 0.38
Compound (SMILES): NC1(c2ccc(-c3nc4c5cccc(O)c5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: SXIOPKJMHPTNBI-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 406.49, ALogP 5.26, HBA 5, HBD 2, PSA 76.44, QED 0.43
Compound (SMILES): NC(=O)/C=C/c1cccc2c1nn1cc(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc21
InChIKey: YLJFAOLMBZALEK-NTCAYCPXSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 459.55, ALogP 5.05, HBA 5, HBD 2, PSA 99.3, QED 0.36
Compound (SMILES): NC1(c2ccc(-c3nc4c5ccc(-c6ccn[nH]6)cc5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: LOGJJQOVSPORPX-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 456.55, ALogP 5.94, HBA 5, HBD 2, PSA 84.89, QED 0.34
Compound (SMILES): Cc1cc(-c2ccc3c(c2)nn2cc(-c4ccccc4)c(-c4ccc(C5(N)CCC5)cc4)nc32)[nH]n1
InChIKey: GBFZNKFZCTYQEA-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 470.58, ALogP 6.25, HBA 5, HBD 2, PSA 84.89, QED 0.32
Compound (SMILES): NC1(c2ccc(-c3nc4c5cc(-c6ccn[nH]6)ccc5nn4cc3-c3ccccc3)cc2)CCC1
InChIKey: XWQRUJWZWABOEM-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 456.55, ALogP 5.94, HBA 5, HBD 2, PSA 84.89, QED 0.34
Compound (SMILES): Cc1cc(-c2ccc3nn4cc(-c5ccccc5)c(-c5ccc(C6(N)CCC6)cc5)nc4c3c2)[nH]n1
InChIKey: LWEFXVZPXAYCPI-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 470.58, ALogP 6.25, HBA 5, HBD 2, PSA 84.89, QED 0.32
Compound (SMILES): COC(=O)/C=C/c1ccc2nn3cc(-c4ccccc4)c(-c4ccc(C5(N)CCC5)cc4)nc3c2c1
InChIKey: JUWVBOLQKJABNO-OQLLNIDSSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 474.56, ALogP 5.74, HBA 6, HBD 1, PSA 82.51, QED 0.26
Compound (SMILES): NC(=O)/C=C/c1ccc2nn3cc(-c4ccccc4)c(-c4ccc(C5(N)CCC5)cc4)nc3c2c1
InChIKey: QLSSHTPYLBECMR-RIYZIHGNSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET assay: For the assay 50 nl of a 100fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 ul => final cone, in the 5 ul assay volume is 10 ul) and substrate (1 .67 ul => final cone, in the 5 ul assay volume is 1 ul) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 459.55, ALogP 5.05, HBA 5, HBD 2, PSA 99.3, QED 0.36
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: WAWNWRVGWKZVLT-HYHVOXATSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 718.95, ALogP 5.76, HBA 9, HBD 3, PSA 136.99, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@@H](O)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: WAWNWRVGWKZVLT-CFTUFJLTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 718.95, ALogP 5.76, HBA 9, HBD 3, PSA 136.99, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](CC[C@@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: WAWNWRVGWKZVLT-YUXCJTBFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 718.95, ALogP 5.76, HBA 9, HBD 3, PSA 136.99, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2CSC[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: YCLPMWDXYKCXAX-PUCLRWMGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 720.99, ALogP 6.7, HBA 9, HBD 2, PSA 116.76, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2CS(=O)(=O)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: VLNZCNIBUVLVDW-PUCLRWMGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 752.99, ALogP 5.38, HBA 10, HBD 2, PSA 150.9, QED 0.16
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)NC2(C(=O)N[C@H](CC[C@H](Cc3ccccc3)NC(=O)OCc3cncs3)Cc3ccccc3)CCN(C)CC2)cs1
InChIKey: PFESJDCERSQSIQ-ROJLCIKYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 746.02, ALogP 6.37, HBA 9, HBD 3, PSA 128.79, QED 0.12
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2CCN(C)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: MGUFMPBNVRJNSL-PSUXHBTPSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 731.99, ALogP 5.94, HBA 9, HBD 2, PSA 120, QED 0.16
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@@H](N)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: MAACKGCFQFNWKO-PIGLOVQCSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 717.96, ALogP 5.72, HBA 9, HBD 3, PSA 142.78, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@@H](N3CCOCC3)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: CZSVRXPBPZIVEN-WSQFZFBESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 788.05, ALogP 6.1, HBA 10, HBD 2, PSA 129.23, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@H](N3CCOCC3)C[C@H]2C(=O)N[C@@H](CC[C@@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: CZSVRXPBPZIVEN-PYPNIHNUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 788.05, ALogP 6.1, HBA 10, HBD 2, PSA 129.23, QED 0.14
Compound (SMILES): CC(=O)N[C@H]1C[C@@H](C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)N(C(=O)N(C)Cc2csc(C(C)C)n2)C1
InChIKey: GTQUHFLNJSGNRA-UWEBUPBHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 760, ALogP 5.9, HBA 9, HBD 3, PSA 145.86, QED 0.13
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2CCC[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: CJGMOBVTWWMPMK-QSCLJHCWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 702.95, ALogP 6.78, HBA 8, HBD 2, PSA 116.76, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2CCC[C@@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: CJGMOBVTWWMPMK-ZAPWPRAASA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 702.95, ALogP 6.78, HBA 8, HBD 2, PSA 116.76, QED 0.14
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2Cc3nc[nH]c3C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: YUTMPZJGRVRLLE-USIGKAAMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 754.98, ALogP 6.47, HBA 9, HBD 3, PSA 145.44, QED 0.11
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)NC2(C(=O)N[C@H](CC[C@H](Cc3ccccc3)NC(=O)OCc3cncs3)Cc3ccccc3)CCNCC2)cs1
InChIKey: QSJUJJFEVZDXSW-FIRIVFDPSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 731.99, ALogP 6.03, HBA 9, HBD 4, PSA 137.58, QED 0.11
Compound (SMILES): CN[C@H]1C[C@@H](C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)N(C(=O)N(C)Cc2csc(C(C)C)n2)C1
InChIKey: HQAFPESZZWFRFI-XDUPDYOVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 731.99, ALogP 5.98, HBA 9, HBD 3, PSA 128.79, QED 0.13
Compound (SMILES): CC(C)c1nc(CN(C)C(=O)N2C[C@@H](N(C)C)C[C@H]2C(=O)N[C@H](CC[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)Cc2ccccc2)cs1
InChIKey: KSIVSAIIPBDCII-LKMBZGFLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 746.02, ALogP 6.32, HBA 9, HBD 2, PSA 120, QED 0.14
Compound (SMILES): C=CCC(C(=O)NCCS(N)(=O)=O)c1nc2ccc(-c3ccccc3)cc2s1
InChIKey: ZNLBNHGHXRFTTE-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 415.54, ALogP 3.03, HBA 5, HBD 2, PSA 102.15, QED 0.55
Compound (SMILES): CC(C)c1cc(CNC(=O)C(C)(C)c2nc3ccc(-c4ccccc4)cc3s2)on1
InChIKey: UVHGBTYSDWIAPE-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 > 62000 nM (pChEMBL 4.208000183105469)
Descriptors: MW 419.55, ALogP 5.67, HBA 5, HBD 1, PSA 68.02, QED 0.44
Compound (SMILES): Cc1cc(CNC(=O)C(C)(C)c2nc3ccc(-c4ccccc4)cc3s2)on1
InChIKey: KKMHSJYFABZMSG-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 > 62000 nM (pChEMBL 4.208000183105469)
Descriptors: MW 391.5, ALogP 4.85, HBA 5, HBD 1, PSA 68.02, QED 0.53
Compound (SMILES): NS(=O)(=O)CCNC(=O)C(NC(=O)c1cccnc1)c1nc2ccc(-c3ccc(F)nc3)cc2s1
InChIKey: IRVJIWMKAMBODQ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 514.56, ALogP 1.77, HBA 8, HBD 3, PSA 157.03, QED 0.3
Compound (SMILES): CCCC(=O)NC(C(=O)NCCS(N)(=O)=O)c1nc2ccc(-c3ccc(F)nc3)cc2s1
InChIKey: SOHDTVKWPDYKIR-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 479.56, ALogP 1.86, HBA 7, HBD 3, PSA 144.14, QED 0.4