lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(-c2cc(C(C)N3CCOCC3)cnc2Nc2cnc(Cl)c(NS(=O)(=O)N(C)C)c2)c2nc[nH]c2n1
InChIKey: HUZVARWZIFWJRG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 573.08, ALogP 3.13, HBA 10, HBD 3, PSA 154.15, QED 0.27
Compound (SMILES): COc1cc(Nc2ncc([C@@H](C)N3CCN(S(C)(=O)=O)CC3)cc2-c2nc(C)nc(N)n2)cnc1Cl
InChIKey: OGHNBXFEDHZOJG-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 534.05, ALogP 2.26, HBA 11, HBD 2, PSA 152.35, QED 0.43
Compound (SMILES): COc1cc(Nc2ncc(C(C)(C)O)cc2-c2nc(C)nc(N)n2)cnc1Cl
InChIKey: PUMWJWJEHSCNLG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 474 nM (pChEMBL 6.320000171661377)
Descriptors: MW 401.86, ALogP 2.85, HBA 9, HBD 3, PSA 131.96, QED 0.55
Compound (SMILES): COc1ncc(Nc2ncc(C3=CCOCC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: BMLDGTMESKPSCM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 409.43, ALogP 2.91, HBA 9, HBD 2, PSA 120.96, QED 0.65
Compound (SMILES): COc1ncc(Nc2ncc(C3CCOCC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: YPNHYSURJIOHHL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.44, ALogP 3, HBA 9, HBD 2, PSA 120.96, QED 0.65
Compound (SMILES): COc1ncc(Nc2ncc(C(C)(C)O)cc2-c2cc(N)nc(C)n2)cc1F
InChIKey: WRDZQSWCULXFCM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.42, ALogP 2.94, HBA 8, HBD 3, PSA 119.07, QED 0.61
Compound (SMILES): COc1ncc(Nc2ncc(C(C)(C)C(=O)O)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: BPKLYAPVXXJVLM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.41, ALogP 2.47, HBA 9, HBD 3, PSA 149.03, QED 0.55
Compound (SMILES): COc1ncc(Nc2ncc(C(O)C(C)(C)O)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: LYAQKDDXVAENGV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.43, ALogP 1.91, HBA 10, HBD 4, PSA 152.19, QED 0.47
Compound (SMILES): COc1ncc(Nc2ncc(C(C)O)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: RFMMTRCKHHKIJM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 371.38, ALogP 2.16, HBA 9, HBD 3, PSA 131.96, QED 0.62
Compound (SMILES): COc1ncc(Nc2ncc(C(OC(=O)c3cccc(Cl)c3)C(C)(C)O)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: NZXIRKWJXSSTSF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 553.98, ALogP 4.43, HBA 11, HBD 3, PSA 158.26, QED 0.26
Compound (SMILES): COc1ncc(Nc2ncc(CN3CCN(C(=O)N(C)C(C)C)CC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: GKJBCVKYWRHTBK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.61, ALogP 2.69, HBA 10, HBD 2, PSA 138.52, QED 0.47
Compound (SMILES): COc1ncc(Nc2ncc(CN3CCN(C(=O)N(C)CC(F)(F)F)CC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: SORWEBKDPVFLGQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 1745 nM (pChEMBL 5.760000228881836)
Descriptors: MW 564.55, ALogP 2.84, HBA 10, HBD 2, PSA 138.52, QED 0.41
Compound (SMILES): COc1ncc(Nc2ncc(CN3CCN(C(=O)N(C)C4CC4)CC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: JQLIHCFYFGWBRN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 2990 nM (pChEMBL 5.519999980926514)
Descriptors: MW 522.59, ALogP 2.44, HBA 10, HBD 2, PSA 138.52, QED 0.48
Compound (SMILES): COc1ncc(Nc2ncc([C@@H](C)N3CCN(S(C)(=O)=O)C[C@@H]3C)cc2-c2nc(C)nc(N)n2)cn1
InChIKey: MMHAEDBURINXPB-UONOGXRCSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 1209 nM (pChEMBL 5.920000076293945)
Descriptors: MW 514.62, ALogP 1.39, HBA 12, HBD 2, PSA 165.24, QED 0.47
Compound (SMILES): Cc1nc(N)nc(-c2cc([C@@H](C)N3CCN(S(C)(=O)=O)C[C@@H]3C)cnc2Nc2ccc(Cl)nc2)n1
InChIKey: ONMGCBGGUDMPHS-UONOGXRCSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.05, ALogP 2.64, HBA 10, HBD 2, PSA 143.12, QED 0.47
Compound (SMILES): COc1ncc(Nc2ncc(CN3CCN(S(C)(=O)=O)[C@H](C)C3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: GHVPGSGUWBIKOC-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 517.59, ALogP 1.58, HBA 11, HBD 2, PSA 152.35, QED 0.47
Compound (SMILES): COc1cnc(Nc2cnc(Cl)c(N)c2)c(-c2nc(C)nc(N)n2)c1
InChIKey: VXIFMJZIIDYJBM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 358.79, ALogP 2.21, HBA 9, HBD 3, PSA 137.75, QED 0.6
Compound (SMILES): Cc1nc(N)nc(-c2cc(C(C)N3CCOCC3)cnc2Nc2cnc(Cl)c(NS(C)(=O)=O)c2)n1
InChIKey: ZTTNCSHFSRNEAI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In Vitro Inhibition Assay: The Invitrogen (Carlsbad, Calif.) mammalian target of rapamycin (mTOR) Lanthascreen assay can be used to quantitate mTOR kinase activity in an in vitro setting. Active mTOR phosphorylates eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) on residue threonine 46. This phosphorylation event can be detected with a phospho-specific terbium (Tb) labeled Ab, in turn bringing the Tb label in close proximity to the GFP tagged 4E-BP1 and allowing for time-resolved fluorescence resonance energy transfer (TR-FRET), which correlates 4E-BP1 phosphorylation levels with mTOR kinase activity.
Measurement: IC50 = 472 nM (pChEMBL 6.329999923706055)
Descriptors: MW 520.02, ALogP 2.38, HBA 11, HBD 3, PSA 161.14, QED 0.39
Compound (SMILES): COc1ccc(S(=O)(=O)N(CC(C)C)CC(O)C(Cc2ccccc2)NC(=O)OC2COC3OCC(OCc4ccccc4)C23)cc1
InChIKey: NVPCFRRKQWRDBN-UHFFFAOYSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolateBRU/LAI) (HIV-1)
UniProt: P03367
Assay: Enzyme Inhibition Assay: The enzyme inhibitory activity (Ki) was determined according to an assay protocol reported by Toth and Marshall (Toth, M. V.; Marshall, G. R. Int. J. Pep. Protein Res. 1990, 36, 544-550).
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 668.81, ALogP 4, HBA 9, HBD 2, PSA 132.86, QED 0.25
Compound (SMILES): O=C(C1CC1)N1CC[C@@H](Cc2n[nH]c(=O)n2-c2ccc(-c3ccc4occc4c3)cc2)C1
InChIKey: AQTPWCUIYUOEMG-INIZCTEOSA-N
Target: Fatty acid synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P49327
Assay: Affinity Biochemical interaction: (enzymatic assay detecting released Coenzyme A) EUB0002242b FASN
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 428.49, ALogP 3.77, HBA 5, HBD 1, PSA 84.13, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCNC(=O)CCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCN)NC1=O
InChIKey: UZXATBDCQWZCAK-IQSCWYJSSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay Using [I125]-NDP-a-MSH: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-α-MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl, 2 mM CaCl2, 2 mM MgCl2, 0.3 mM 1,10-phenanthroline, and 0.2% bovine serum albumin. After incubation for 60 minutes at 37° C., the assay mixture was filtered and the membranes washed three times with ice-cold buffer. Filters were dried and counted in a gamma counter for bound radioactivity. Non-specific binding was measured by inhibition of binding of [I125]-NDP-α-MSH in the presence of 1 uM NDP-α-MSH. Maximal specific binding (100%) was defined as the difference in radioactivity (cpm) bound to cell membranes in the absence and presence of 1 uM NDP-α-MSH. Radioactivity (cpm) obtained in the presence of test compounds was normalized with respect to 100% specific binding to determine the percent inhibition of [I125]-NDP-α-MSH binding. Each assay was conducted in triplicate and the actual mean values are described, with results less than 0% reported as 0%. Ki values for test peptides of the present invention were determined using Graph-Pad Prism curve-fitting software.
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 1030.21
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: SUYDUGVDUFCDHQ-IQSCWYJSSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 1058.22
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: SUYDUGVDUFCDHQ-XEFNOBGUSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 1058.22
Compound (SMILES): CCCCC(=O)N[C@H]1CCC(=O)NCC[C@@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: JUOGFOXGQYCMTJ-BWBQVKFQSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Binding Assay: A competitive inhibition binding assay was performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMCR-1a or hMCR-4 (in each instance where the h prefix refers to human), or alternatively membrane homogenates from B16-F10 mouse melanoma cells containing endogenous murine MCR-1. In the examples that follow, all MCR-1 and MCR-4 values are for human recombinant receptors, unless otherwise noted. Assays were performed in 96 well polypropylene round-bottom plates (VWR catalog number 12777-030). Membrane homogenates were incubated with 0.1 nM [I125]-NDP-α-MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl, 2 mM CaCl2, 2 mM MgCl2, 0.3 mM 1,10-phenanthroline, and 0.2% bovine serum albumin. After incubation for 90 minutes at 37° C., the assay mixture was filtered onto GF/B Unifilter plates (Perkin-Elmer catalog number 6005177) and washed with 3 mL of ice-cold buffer per well. Filters were air dried and 35 uL of scintillation cocktail added to each well. Plates were counted in a Microbeta counter for bound radioactivity. Non-specific binding was measured by inhibition of binding of [I125]-NDP-α-MSH in the presence of 1 uM NDP-α-MSH. Maximal specific binding (100%) was defined as the difference in radioactivity (cpm) bound to cell membranes in the absence and presence of 1 uM NDP-α-MSH. Each assay was conducted in duplicate and the actual mean values are described, with results less than 0% reported as 0%. Ki values for peptides of the present invention were determined using Graph-Pad Prism curve-fitting software.
Measurement: Ki = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 939.09, ALogP -0.93, HBA 10, HBD 13, PSA 353.16, QED 0.03
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: BOAIJXQJMLWMSF-VWUVXGKKSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: GTMASPVXPKDKOK-VWUVXGKKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 0.189 nM (pChEMBL 9.720000267028809)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: BOAIJXQJMLWMSF-GWZAZKCQSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCNC(=O)CCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: FSTDLRINZOKGRA-IQSCWYJSSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 1058.22
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCC(=O)NCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: ZLLOVWBBACAVIV-VWUVXGKKSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC(=O)NCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: HYNXKHHGAXLIEQ-VWUVXGKKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: KOMGNGDDTPNSKC-PDBPWWFNSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 1055.21
Compound (SMILES): COc1ccc(Cn2c(=O)c3cc(OC(CF)CF)ccc3n(C3CCN(C=O)CC3)c2=O)cc1OC
InChIKey: JYHQBYXSPOBQMT-UHFFFAOYSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Enzymatic Assay: By using for PDE8 an enzymatic assay equivalent to that described for PDE7. PDE7 Enzymatic Assay: The assay is carried out in 1.5 ml Eppendorf tubes comprising 40 mM of Tris-HCl (pH 7.5), 15 mM of MgCl2, 1 mM of EGTA, 0.5 mg/ml of bovine serum albumin, 0.063 uCi of [3H]-cAMP (corresponding to a cAMP concentration of between 15 and 25 nM), 10 uM of rolipram and PDE7 in a final volume of 100 ul. The assay is carried out in the absence (control sample) or in the presence (treated sample) of the compounds tested as PDE7 inhibitors. The final concentration of DMSO in the assay is 2%. The reaction is initiated by addition of enzyme and the samples are maintained at ambient temperature for 30 minutes. The enzymatic dilution is adjusted so as to obtain a degree of conversion of 10 to 15%. The enzymatic reaction is halted by immersion of the stoppered Eppendorf tubes in a water bath at 100C. for 3 minutes.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 517.53, ALogP 2.71, HBA 8, HBD 0, PSA 92, QED 0.38
Compound (SMILES): COc1cc(Cn2c(=O)c3cc(OC(CF)CF)ccc3n(C3CCN(C=O)CC3)c2=O)ccc1OCC(=O)N1CCCCC1
InChIKey: BBHYMAIPZZCFDD-UHFFFAOYSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Enzymatic Assay: By using for PDE8 an enzymatic assay equivalent to that described for PDE7. PDE7 Enzymatic Assay: The assay is carried out in 1.5 ml Eppendorf tubes comprising 40 mM of Tris-HCl (pH 7.5), 15 mM of MgCl2, 1 mM of EGTA, 0.5 mg/ml of bovine serum albumin, 0.063 uCi of [3H]-cAMP (corresponding to a cAMP concentration of between 15 and 25 nM), 10 uM of rolipram and PDE7 in a final volume of 100 ul. The assay is carried out in the absence (control sample) or in the presence (treated sample) of the compounds tested as PDE7 inhibitors. The final concentration of DMSO in the assay is 2%. The reaction is initiated by addition of enzyme and the samples are maintained at ambient temperature for 30 minutes. The enzymatic dilution is adjusted so as to obtain a degree of conversion of 10 to 15%. The enzymatic reaction is halted by immersion of the stoppered Eppendorf tubes in a water bath at 100C. for 3 minutes.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 628.67, ALogP 3.09, HBA 9, HBD 0, PSA 112.31, QED 0.28
Compound (SMILES): N#Cc1cc(Cn2c(=O)c3cc(OC(CF)CF)ccc3n(C3CCN(C=O)CC3)c2=O)ccc1-c1ccccc1
InChIKey: ORTHDXKTDAKOBP-UHFFFAOYSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Enzymatic Assay: By using for PDE8 an enzymatic assay equivalent to that described for PDE7. PDE7 Enzymatic Assay: The assay is carried out in 1.5 ml Eppendorf tubes comprising 40 mM of Tris-HCl (pH 7.5), 15 mM of MgCl2, 1 mM of EGTA, 0.5 mg/ml of bovine serum albumin, 0.063 uCi of [3H]-cAMP (corresponding to a cAMP concentration of between 15 and 25 nM), 10 uM of rolipram and PDE7 in a final volume of 100 ul. The assay is carried out in the absence (control sample) or in the presence (treated sample) of the compounds tested as PDE7 inhibitors. The final concentration of DMSO in the assay is 2%. The reaction is initiated by addition of enzyme and the samples are maintained at ambient temperature for 30 minutes. The enzymatic dilution is adjusted so as to obtain a degree of conversion of 10 to 15%. The enzymatic reaction is halted by immersion of the stoppered Eppendorf tubes in a water bath at 100C. for 3 minutes.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 558.59, ALogP 4.23, HBA 7, HBD 0, PSA 97.33, QED 0.29
Compound (SMILES): CO[C@@H]1CCN(c2nc(-c3c(C)ccc4[nH]nc(C)c34)nc3c2CN(c2c(Cl)c(C4CC4)nn2C)CC3)CC1(C)C
InChIKey: GQEOCXVLXYTOAW-HSZRJFAPSA-N
Target: C5a anaphylatoxin chemotactic receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21730
Assay: FLIPR Assay: Compounds were tested for their ability to inhibit C5a-mediated calcium mobilization using a stable cell line over expressing the human C5aR & the Galpha 15 protein on the FLIPR (Fluorescent Imaging Plate Reader) Tetra system. Cells were maintained in culture media containing DMEM (Dulbecco's Modified Eagle Medium) with 4.5 g/L glucose, 10% fetal bovine serum, 100 U/mL, 1x non-essential amino acid, and 250 ug/mL G418 (Geneticin). Prior to testing of compounds, cells were plated at 10,000 cells/well in clear bottom 384-well black plate, and incubated overnight at 37C. with 5% CO2. On the day of experiment, culture media was removed, and replaced with assay buffer HBSS (Hanks' Balanced Salt Solution) with 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) and 0.1% BSA (bovine serum albumin) BSA containing calcium 5 dye (Molecular Devices) and 2.5 mM probenecid. After 1 hour incubation at 37C., 5% CO2 for 60 min, cells were pre-incubated with compounds for 30 minutes.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 575.16, ALogP 5.72, HBA 8, HBD 1, PSA 87.99, QED 0.33
Compound (SMILES): COc1ccc(C)c(N2CCc3nc(-c4c(C)ccc5[nH]ncc45)cc(C)c3C2)c1
InChIKey: AUVDUYXOUMRHMM-UHFFFAOYSA-N
Target: C5a anaphylatoxin chemotactic receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21730
Assay: FLIPR Assay: Compounds were tested for their ability to inhibit C5a-mediated calcium mobilization using a stable cell line over expressing the human C5aR & the Galpha 15 protein on the FLIPR (Fluorescent Imaging Plate Reader) Tetra system. Cells were maintained in culture media containing DMEM (Dulbecco's Modified Eagle Medium) with 4.5 g/L glucose, 10% fetal bovine serum, 100 U/mL, 1x non-essential amino acid, and 250 ug/mL G418 (Geneticin). Prior to testing of compounds, cells were plated at 10,000 cells/well in clear bottom 384-well black plate, and incubated overnight at 37C. with 5% CO2. On the day of experiment, culture media was removed, and replaced with assay buffer HBSS (Hanks' Balanced Salt Solution) with 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) and 0.1% BSA (bovine serum albumin) BSA containing calcium 5 dye (Molecular Devices) and 2.5 mM probenecid. After 1 hour incubation at 37C., 5% CO2 for 60 min, cells were pre-incubated with compounds for 30 minutes.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 398.51, ALogP 5.12, HBA 4, HBD 1, PSA 54.04, QED 0.52
Compound (SMILES): Cc1ccc(C(C)C)cc1N1CCc2nc(-c3c(C)ccc4[nH]ncc34)cc(C)c2C1
InChIKey: JMJCCEXIFUOKLB-UHFFFAOYSA-N
Target: C5a anaphylatoxin chemotactic receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21730
Assay: FLIPR Assay: Compounds were tested for their ability to inhibit C5a-mediated calcium mobilization using a stable cell line over expressing the human C5aR & the Galpha 15 protein on the FLIPR (Fluorescent Imaging Plate Reader) Tetra system. Cells were maintained in culture media containing DMEM (Dulbecco's Modified Eagle Medium) with 4.5 g/L glucose, 10% fetal bovine serum, 100 U/mL, 1x non-essential amino acid, and 250 ug/mL G418 (Geneticin). Prior to testing of compounds, cells were plated at 10,000 cells/well in clear bottom 384-well black plate, and incubated overnight at 37C. with 5% CO2. On the day of experiment, culture media was removed, and replaced with assay buffer HBSS (Hanks' Balanced Salt Solution) with 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) and 0.1% BSA (bovine serum albumin) BSA containing calcium 5 dye (Molecular Devices) and 2.5 mM probenecid. After 1 hour incubation at 37C., 5% CO2 for 60 min, cells were pre-incubated with compounds for 30 minutes.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 410.57, ALogP 6.24, HBA 3, HBD 1, PSA 44.81, QED 0.43
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCO[C@@H]4CCC[C@H]43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: FDBWTMMKIZGUEZ-IEGYKGNPSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 550.06, ALogP 5.07, HBA 9, HBD 1, PSA 114.96, QED 0.37
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCOC4CCCCC43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: UARAEDGQJRIWEY-YTFADCBGSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 564.09, ALogP 5.46, HBA 9, HBD 1, PSA 114.96, QED 0.34
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCO[C@H]4CCC[C@@H]43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: FDBWTMMKIZGUEZ-DODAUVCRSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 550.06, ALogP 5.07, HBA 9, HBD 1, PSA 114.96, QED 0.37