lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(N)nc(-c2cc(CN3CCN(C(=O)N(C)C)CC3)cnc2Nc2cnc(O)c(F)c2)n1
InChIKey: PUBMSBCYCLFVRU-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 482.52, ALogP 1.61, HBA 10, HBD 3, PSA 149.52, QED 0.49
Compound (SMILES): COc1ncc(Nc2ncc([C@@H](C)N3CCOCC3)cc2-c2cc(N)nc(C)n2)cc1F
InChIKey: DODICWVNTJJJPT-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 439.5, ALogP 3.11, HBA 9, HBD 2, PSA 111.31, QED 0.6
Compound (SMILES): COc1ncc(Nc2ncc([C@H](C)N3CCOCC3)cc2-c2nc(C)nc(N)n2)cc1F
InChIKey: NSLPSCGNZPYBNX-LBPRGKRZSA-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 = 4015 nM (pChEMBL 5.400000095367432)
Descriptors: MW 440.48, ALogP 2.5, HBA 10, HBD 2, PSA 124.2, QED 0.59
Compound (SMILES): COc1ccc(Nc2ncc([C@H](O)C(F)(F)F)cc2-c2nc(C)nc(N)n2)cn1
InChIKey: DPFYZQXBFNDDAE-ZDUSSCGKSA-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 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 407.36, ALogP 2.57, HBA 9, HBD 3, PSA 131.96, QED 0.58
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)c(OC)c1
InChIKey: PCLRPJYQKLMMKX-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): COc1cc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)cc(OC)c1OC
InChIKey: DRBBILLFANXMKL-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 391.43, ALogP 2.38, HBA 9, HBD 2, PSA 112.71, QED 0.34
Compound (SMILES): COc1ccc(N/C(=C/[N+](=O)[O-])NCCCn2cncc2C)cc1OC
InChIKey: XGSCKLKAQKSJDK-GZTJUZNOSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 361.4, ALogP 2.38, HBA 8, HBD 2, PSA 103.48, QED 0.38
Compound (SMILES): Cc1cncn1CCCCN/C(=C\[N+](=O)[O-])NC1CCCCC1
InChIKey: KJDYILRPNDWKLG-FOWTUZBSSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 321.43, ALogP 2.56, HBA 6, HBD 2, PSA 85.02, QED 0.41
Compound (SMILES): Cc1cncn1CCCN/C(=C\[N+](=O)[O-])Nc1ccc2c(c1)OCO2
InChIKey: JUISCZDVYAJMBT-CXUHLZMHSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 345.36, ALogP 2.09, HBA 8, HBD 2, PSA 103.48, QED 0.43
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])NC1CCCCC1
InChIKey: YAPJFJYUXSGRHO-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 307.4, ALogP 2.18, HBA 5, HBD 1, PSA 85.35, QED 0.27
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc(Cl)cc1
InChIKey: OVKWACFPXWSZFC-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 335.8, ALogP 3.02, HBA 5, HBD 1, PSA 85.35, QED 0.28
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc(C(F)(F)F)cc1
InChIKey: GPQHOIQTHKOAGY-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 369.35, ALogP 3.39, HBA 5, HBD 1, PSA 85.35, QED 0.27
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1cccc2ccccc12
InChIKey: AMQXTNLKQTXNJU-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 351.41, ALogP 3.52, HBA 5, HBD 1, PSA 85.35, QED 0.23
Compound (SMILES): Cc1cncn1CCC/N=C(\C[N+](=O)[O-])Nc1ccc2c(c1)OCCO2
InChIKey: MZYLSVFGZFWYEJ-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Fluorometric Assay: All measurements were performed with a BioAssay Reader HTS-7000Plus for microplates (Perkin Elmer) at 30C. QC activity was evaluated fluorometrically using H-Gln-beta NA. The samples consisted of 0.2 mM fluorogenic substrate, 0.25 U pyroglutamyl aminopeptidase (Unizyme, Horsholm, Denmark) in 0.2 M Tris/HCl, pH 8.0 containing 20 mM EDTA and an appropriately diluted aliquot of QC in a final volume of 250 ul. Excitation/emission wavelengths were 320/410 nm. The assay reactions were initiated by addition of glutaminyl cyclase. QC activity was determined from a standard curve of beta -naphthylamine under assay conditions. One unit is defined as the amount of QC catalyzing the formation of 1 umol pGlu-beta NA from H-Gln-beta NA per minute under the described conditions. In a second fluorometric assay, QC was activity determined using H-Gln-AMC as substrate. Reactions were carried out at 30C. utilizing the NOVOStar reader for microplates (BMG labtechnologies).
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 359.39, ALogP 2.14, HBA 7, HBD 1, PSA 103.81, QED 0.27
Compound (SMILES): COc1ccc(NC(=O)Nc2ccc3cc(C(=O)N[C@H]4CN5CCC4CC5)sc3c2)cc1
InChIKey: VAEDYBLXCIOINJ-FQEVSTJZSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Alpha 7 UAChR Inhibition Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. in Neuropharmacol, 1999, 38, 679-690.Rat brain tissue (hippocampus or whole brain) is homogenized in aqueous homogenization buffer (10% w/v, 0.32 M sucrose, 1 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4° C.) at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000×g, 4° C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000×g, 4° C., 10 min). The two supernatants are combined and centrifuged (15 000×g, 4° C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is suspended in binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and the suspension is centrifuged (15 000×g, 4° C., 30 min), twice.The residue is resuspended in binding buffer to a concentration of 4 mg/ml and incubated in a volume of 250 μl (amount of membrane protein 0.4 mg) in the presence of 2 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 60 min.Incubation is then carried out in the presence of 1 μM α-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine). The incubation is stopped by adding 4 ml of PBS (20 mM Na2HPO4, 5 mM KH2PO4, 150 mM NaCl, pH 7.4, 4° C.) and filtering through type A/E glass fiber filters (Gelman Sciences) which have previously been placed in 0.3% (v/v) polyethyleneirnine (PEI) for 3 h. The filters are washed twice with 4 ml of PBS (4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance was determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]-methyllycaconitine using the equation K1=IC50/(1+L/KD).In place of [3H]-methyllycaconitine it is also possible to employ other α7 nAChR-selective radioligands such as, for example, [125I]-α-bungarotoxin or nonselective nAChR radioligands together with inhibitors of other nAChRs.The in vitro data for the effects of the compounds of the invention show a Ki of <300 nM.
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 450.56, ALogP 4.38, HBA 5, HBD 3, PSA 82.7, QED 0.54
Compound (SMILES): O=C(NCCc1ccccc1)Nc1ccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc2c1
InChIKey: MORUDEMULGREIK-NRFANRHFSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: 5-HT3 Receptor Assay: Membranes from HEK293 cells which express recombinant human 5-HT3 receptor (RB-HS3, Receptor Biology, Inc., MD, USA) are diluted in accordance with the manufacturer's instructions in incubation buffer (50 mM tris base, pH 7.4, 5 mM MgCl2, 0.5 mM EDTA, 0.1% (w/v) ascorbic acid, 10 μM pargyline and incubated in a volume of 200 μl (amount of membrane protein 3 μg) in the presence of 0.5 nM of the selective 5-HT3 receptor radio ligand [3H]-GR65630 (NET 1011, Du Pont) and various concentrations of the test substance at 21° C. for 60 min. The nonspecific binding is determined by incubation in the presence of 100 μM 5-HT (5-hydroxytryptamine). The incubation is stopped by filtering through type A/E glass fiber filters (Gelman Sciences) or GF/B filters (Whatman) which have previously been placed in 0.3% (v/v) polyethyleneimine (PEI) for at least 1 h. The filters are washed three times with 3 ml of washing buffer (50 mM Tris-HCl, pH 7.4; 4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance is determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]GR65630 (Ki=IC50/(1+L/KD)).
Measurement: Ki = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 448.59, ALogP 4.09, HBA 4, HBD 3, PSA 73.47, QED 0.53
Compound (SMILES): N#Cc1cccc(NC(=O)Nc2ccc3cc(C(=O)N[C@H]4CN5CCC4CC5)sc3c2)c1
InChIKey: QNQOVTZANISRRO-FQEVSTJZSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: 5-HT3 Receptor Assay: Membranes from HEK293 cells which express recombinant human 5-HT3 receptor (RB-HS3, Receptor Biology, Inc., MD, USA) are diluted in accordance with the manufacturer's instructions in incubation buffer (50 mM tris base, pH 7.4, 5 mM MgCl2, 0.5 mM EDTA, 0.1% (w/v) ascorbic acid, 10 μM pargyline and incubated in a volume of 200 μl (amount of membrane protein 3 μg) in the presence of 0.5 nM of the selective 5-HT3 receptor radio ligand [3H]-GR65630 (NET 1011, Du Pont) and various concentrations of the test substance at 21° C. for 60 min. The nonspecific binding is determined by incubation in the presence of 100 μM 5-HT (5-hydroxytryptamine). The incubation is stopped by filtering through type A/E glass fiber filters (Gelman Sciences) or GF/B filters (Whatman) which have previously been placed in 0.3% (v/v) polyethyleneimine (PEI) for at least 1 h. The filters are washed three times with 3 ml of washing buffer (50 mM Tris-HCl, pH 7.4; 4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance is determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]GR65630 (Ki=IC50/(1+L/KD)).
Measurement: Ki = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 445.55, ALogP 4.24, HBA 5, HBD 3, PSA 97.26, QED 0.56
Compound (SMILES): O=C(Nc1ccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc2c1)Nc1c(F)cccc1F
InChIKey: UOKZDYDZJJPEDZ-SFHVURJKSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: 5-HT3 Receptor Assay: Membranes from HEK293 cells which express recombinant human 5-HT3 receptor (RB-HS3, Receptor Biology, Inc., MD, USA) are diluted in accordance with the manufacturer's instructions in incubation buffer (50 mM tris base, pH 7.4, 5 mM MgCl2, 0.5 mM EDTA, 0.1% (w/v) ascorbic acid, 10 μM pargyline and incubated in a volume of 200 μl (amount of membrane protein 3 μg) in the presence of 0.5 nM of the selective 5-HT3 receptor radio ligand [3H]-GR65630 (NET 1011, Du Pont) and various concentrations of the test substance at 21° C. for 60 min. The nonspecific binding is determined by incubation in the presence of 100 μM 5-HT (5-hydroxytryptamine). The incubation is stopped by filtering through type A/E glass fiber filters (Gelman Sciences) or GF/B filters (Whatman) which have previously been placed in 0.3% (v/v) polyethyleneimine (PEI) for at least 1 h. The filters are washed three times with 3 ml of washing buffer (50 mM Tris-HCl, pH 7.4; 4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance is determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]GR65630 (Ki=IC50/(1+L/KD)).
Measurement: Ki = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 456.52, ALogP 4.65, HBA 4, HBD 3, PSA 73.47, QED 0.54
Compound (SMILES): COc1cccc(NC(=O)Nc2ccc3cc(C(=O)N[C@H]4CN5CCC4CC5)sc3c2)c1
InChIKey: YTFKYVRHCVUFIO-FQEVSTJZSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Alpha 7 UAChR Inhibition Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. in Neuropharmacol, 1999, 38, 679-690.Rat brain tissue (hippocampus or whole brain) is homogenized in aqueous homogenization buffer (10% w/v, 0.32 M sucrose, 1 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4° C.) at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000×g, 4° C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000×g, 4° C., 10 min). The two supernatants are combined and centrifuged (15 000×g, 4° C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is suspended in binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and the suspension is centrifuged (15 000×g, 4° C., 30 min), twice.The residue is resuspended in binding buffer to a concentration of 4 mg/ml and incubated in a volume of 250 μl (amount of membrane protein 0.4 mg) in the presence of 2 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 60 min.Incubation is then carried out in the presence of 1 μM α-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine). The incubation is stopped by adding 4 ml of PBS (20 mM Na2HPO4, 5 mM KH2PO4, 150 mM NaCl, pH 7.4, 4° C.) and filtering through type A/E glass fiber filters (Gelman Sciences) which have previously been placed in 0.3% (v/v) polyethyleneirnine (PEI) for 3 h. The filters are washed twice with 4 ml of PBS (4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance was determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]-methyllycaconitine using the equation K1=IC50/(1+L/KD).In place of [3H]-methyllycaconitine it is also possible to employ other α7 nAChR-selective radioligands such as, for example, [125I]-α-bungarotoxin or nonselective nAChR radioligands together with inhibitors of other nAChRs.The in vitro data for the effects of the compounds of the invention show a Ki of <300 nM.
Measurement: Ki = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 450.56, ALogP 4.38, HBA 5, HBD 3, PSA 82.7, QED 0.54
Compound (SMILES): O=C(Nc1ccccc1)Nc1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc12
InChIKey: VOEZCTHQVJCHAX-IBGZPJMESA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Alpha 7 UAChR Inhibition Assay: The [3H]-methyllycaconitine binding assay is a modification of the method described by Davies et al. in Neuropharmacol, 1999, 38, 679-690.Rat brain tissue (hippocampus or whole brain) is homogenized in aqueous homogenization buffer (10% w/v, 0.32 M sucrose, 1 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4° C.) at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000×g, 4° C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000×g, 4° C., 10 min). The two supernatants are combined and centrifuged (15 000×g, 4° C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is suspended in binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and the suspension is centrifuged (15 000×g, 4° C., 30 min), twice.The residue is resuspended in binding buffer to a concentration of 4 mg/ml and incubated in a volume of 250 μl (amount of membrane protein 0.4 mg) in the presence of 2 nM [3H]-methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance at 21° C. for 60 min.Incubation is then carried out in the presence of 1 μM α-bungarotoxin or 100 μM nicotine or 10 μM MLA (methyllycaconitine). The incubation is stopped by adding 4 ml of PBS (20 mM Na2HPO4, 5 mM KH2PO4, 150 mM NaCl, pH 7.4, 4° C.) and filtering through type A/E glass fiber filters (Gelman Sciences) which have previously been placed in 0.3% (v/v) polyethyleneirnine (PEI) for 3 h. The filters are washed twice with 4 ml of PBS (4° C.), and the bound radioactivity is determined by scintillation measurement. All the assays are carried out in triplicate. The dissociation constant Ki of the test substance was determined from the IC50 of the compounds (concentration of the test substance at which 50% of the ligand bound to the receptor is displaced), the dissociation constant KD and the concentration L of [3H]-methyllycaconitine using the equation K1=IC50/(1+L/KD).In place of [3H]-methyllycaconitine it is also possible to employ other α7 nAChR-selective radioligands such as, for example, [125I]-α-bungarotoxin or nonselective nAChR radioligands together with inhibitors of other nAChRs.The in vitro data for the effects of the compounds of the invention show a Ki of <300 nM.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 420.54, ALogP 4.37, HBA 4, HBD 3, PSA 73.47, QED 0.59
Compound (SMILES): CC1CCC(NCc2ccn(Cc3ccccc3)c(=O)c2O)CC1
InChIKey: VJHCNYYTYSQTGD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 27400 nM (pChEMBL 4.559999942779541)
Descriptors: MW 326.44, ALogP 3.27, HBA 4, HBD 2, PSA 54.26, QED 0.89
Compound (SMILES): O=c1c(O)c(CNCCCn2ccnc2)ccn1Cc1ccccc1
InChIKey: VKLSJRDNBKOSAR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 42500 nM (pChEMBL 4.369999885559082)
Descriptors: MW 338.41, ALogP 1.98, HBA 6, HBD 2, PSA 72.08, QED 0.62
Compound (SMILES): CC(NCc1ccn(Cc2ccccc2)c(=O)c1O)c1ccccc1
InChIKey: VGDRCKOTQHHWTA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 334.42, ALogP 3.45, HBA 4, HBD 2, PSA 54.26, QED 0.73
Compound (SMILES): CSCCNCc1ccn(Cc2ccccc2)c(=O)c1O
InChIKey: QGEIIBDJASWVRH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 304.42, ALogP 2.05, HBA 5, HBD 2, PSA 54.26, QED 0.77
Compound (SMILES): O=c1c(O)c(CN2CCN(c3ccc(Cl)nn3)CC2)ccn1Cc1ccccc1
InChIKey: TXYBXEDSXGTMIV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 411.89, ALogP 2.37, HBA 7, HBD 1, PSA 74.49, QED 0.69
Compound (SMILES): O=C1NCCCCC1NCc1ccn(Cc2ccccc2)c(=O)c1O
InChIKey: UTHFJVFVBLVONK-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 62900 nM (pChEMBL 4.199999809265137)
Descriptors: MW 341.41, ALogP 1.36, HBA 5, HBD 3, PSA 83.36, QED 0.77
Compound (SMILES): O=c1c(O)c(CN2CCN(Cc3ccccc3)CC2)ccn1Cc1ccccc1
InChIKey: YIROCWNERWBGFO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 12600 nM (pChEMBL 4.900000095367432)
Descriptors: MW 389.5, ALogP 2.92, HBA 5, HBD 1, PSA 48.71, QED 0.7
Compound (SMILES): O=c1c(O)c(CN2CCCCCC2)ccn1Cc1ccccc1CO
InChIKey: SEDQAFVMDOBVEF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 29200 nM (pChEMBL 4.539999961853027)
Descriptors: MW 342.44, ALogP 2.47, HBA 5, HBD 2, PSA 65.7, QED 0.88
Compound (SMILES): Cc1ccc(S(=O)(=O)n2ccc(CN3CCC(N4CCCCC4)CC3)c(O)c2=O)cc1
InChIKey: ADTSWGMSEGSYRB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 445.59, ALogP 2.55, HBA 7, HBD 1, PSA 82.85, QED 0.76
Compound (SMILES): Cc1ccc(S(=O)(=O)n2ccc(CN3CCN(c4ccc(Cl)nn4)CC3)c(O)c2=O)cc1
InChIKey: WKOHXGUFCXFRQQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 475.96, ALogP 1.86, HBA 9, HBD 1, PSA 108.63, QED 0.6
Compound (SMILES): O=c1c(O)c(CNCc2ccccc2)ccn1Cc1ccc(Cl)cc1
InChIKey: SJYNBRCAAHWFJE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 354.84, ALogP 3.55, HBA 4, HBD 2, PSA 54.26, QED 0.71
Compound (SMILES): Cc1ccc(S(=O)(=O)n2ccc(CN(C)CC(=O)O)c(O)c2=O)cc1
InChIKey: SUGKSHMYQZJYRO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 366.4, ALogP 0.62, HBA 7, HBD 2, PSA 116.91, QED 0.77
Compound (SMILES): O=c1c(O)cccn1Cc1ccc(Cl)cc1
InChIKey: WFROSYVMUUJSPL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 235.67, ALogP 2.26, HBA 3, HBD 1, PSA 42.23, QED 0.87
Compound (SMILES): O=c1c(O)cccn1Cc1cccc(Cl)c1
InChIKey: VIWSANOEUHNZFR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: ELISA assay using VEGF.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 235.67, ALogP 2.26, HBA 3, HBD 1, PSA 42.23, QED 0.87
Compound (SMILES): CN1C(=O)[C@@H](Cc2ccc(-c3cn[nH]c3)cc2)NC(=O)c2cc(Cl)ccc21
InChIKey: MPYUKVIQGNHMJS-QGZVFWFLSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition Assay: In a final reaction volume of 25 uL, ROCK-II (h, amino acids 11-552) (5-10 mU) was incubated with 50 mM Tris pH 7.5, 0.1 mM EGTA, 30 [uM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 10 mM magnesium acetate and gamma-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction was initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of 5 uL of a 3% phosphoric acid solution. 10 uL of the reaction was then spotted onto a P30 filter-mat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 380.84, ALogP 3.05, HBA 3, HBD 2, PSA 78.09, QED 0.73
Compound (SMILES): CN1C(=O)[C@@H](Cc2ccc(-c3ccnc(N)c3)cc2)NC(=O)c2cc(Cl)ccc21
InChIKey: LEQJKROPWKTJPY-GOSISDBHSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition Assay: In a final reaction volume of 25 uL, ROCK-II (h, amino acids 11-552) (5-10 mU) was incubated with 50 mM Tris pH 7.5, 0.1 mM EGTA, 30 [uM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 10 mM magnesium acetate and gamma-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction was initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of 5 uL of a 3% phosphoric acid solution. 10 uL of the reaction was then spotted onto a P30 filter-mat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 406.87, ALogP 3.3, HBA 4, HBD 2, PSA 88.32, QED 0.7
Compound (SMILES): COc1ccc2c(c1)C(=O)N[C@@H](Cc1ccc(-c3ccnc(N)c3)cc1)C(=O)N2C
InChIKey: QRURHEBCZYOJOF-IBGZPJMESA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition Assay: In a final reaction volume of 25 uL, ROCK-II (h, amino acids 11-552) (5-10 mU) was incubated with 50 mM Tris pH 7.5, 0.1 mM EGTA, 30 [uM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 10 mM magnesium acetate and gamma-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction was initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of 5 uL of a 3% phosphoric acid solution. 10 uL of the reaction was then spotted onto a P30 filter-mat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 402.45, ALogP 2.66, HBA 5, HBD 2, PSA 97.55, QED 0.7
Compound (SMILES): CN1C(=O)[C@H](Cc2ccc(-c3ccnc4[nH]ccc34)cc2)NC(=O)c2cc(Cl)ccc21
InChIKey: HTGMQNUJODTQNX-FQEVSTJZSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition Assay: In a final reaction volume of 25 uL, ROCK-II (h, amino acids 11-552) (5-10 mU) was incubated with 50 mM Tris pH 7.5, 0.1 mM EGTA, 30 [uM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 10 mM magnesium acetate and gamma-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction was initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of 5 uL of a 3% phosphoric acid solution. 10 uL of the reaction was then spotted onto a P30 filter-mat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 430.9, ALogP 4.2, HBA 3, HBD 2, PSA 78.09, QED 0.51
Compound (SMILES): COc1ccc2c(c1)C(=O)N[C@@H](Cc1ccc(-c3ccnc4[nH]ccc34)cc1)C(=O)N2C
InChIKey: DVDJHQZUJJBYLZ-NRFANRHFSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition Assay: In a final reaction volume of 25 uL, ROCK-II (h, amino acids 11-552) (5-10 mU) was incubated with 50 mM Tris pH 7.5, 0.1 mM EGTA, 30 [uM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 10 mM magnesium acetate and gamma-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction was initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of 5 uL of a 3% phosphoric acid solution. 10 uL of the reaction was then spotted onto a P30 filter-mat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 426.48, ALogP 3.56, HBA 4, HBD 2, PSA 87.32, QED 0.52
Compound (SMILES): NC(=O)OC(CCN1CCN(c2ccccn2)CC1)c1ccccc1
InChIKey: MXHHMSOYGOLVRZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Binding Assay: 6-week-old Sprague-Dawley (SD) rats were anesthetized in an ether container for 5 minutes, brains were separated from rats, and cortical regions were then separated from the brains of the rats. The cortical regions of the rats were put into a Tris-HCl buffer solution (50 mM, pH 7.7) and homogenized, and the homogenate was centrifuged twice at 4 C. at a rotary speed of 50,000 g to obtain a precipitate (membrane protein). The precipitate was put into a buffer solution, and homogenized, which was used later as a protein source. 0.5 nM [3H]-Ketanserin was used as a radioactive isotope, and 10 uM serotonin was used to remove non-specific bindings. 25 ul of the compound, 100 ul of an aqueous radioactive isotope solution, and 100 ul of the protein source were put together, and kept at 25 C. for 1 hour. The resulting mixture was filtered with a membrane filter in a 96-well harvester when the 96-well plate reaction was completed.
Measurement: IC50 = 448 nM (pChEMBL 6.349999904632568)
Descriptors: MW 340.43, ALogP 2.43, HBA 5, HBD 1, PSA 71.69, QED 0.87
Compound (SMILES): NC(=O)OC(CCN1CCN(C(c2ccc(F)cc2)c2ccc(F)cc2)CC1)c1ccccc1
InChIKey: JIZYOUDLXROXIQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Binding Assay: 6-week-old Sprague-Dawley (SD) rats were anesthetized in an ether container for 5 minutes, brains were separated from rats, and cortical regions were then separated from the brains of the rats. The cortical regions of the rats were put into a Tris-HCl buffer solution (50 mM, pH 7.7) and homogenized, and the homogenate was centrifuged twice at 4 C. at a rotary speed of 50,000 g to obtain a precipitate (membrane protein). The precipitate was put into a buffer solution, and homogenized, which was used later as a protein source. 0.5 nM [3H]-Ketanserin was used as a radioactive isotope, and 10 uM serotonin was used to remove non-specific bindings. 25 ul of the compound, 100 ul of an aqueous radioactive isotope solution, and 100 ul of the protein source were put together, and kept at 25 C. for 1 hour. The resulting mixture was filtered with a membrane filter in a 96-well harvester when the 96-well plate reaction was completed.
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 465.54, ALogP 4.9, HBA 4, HBD 1, PSA 58.8, QED 0.51
Compound (SMILES): NC(=O)OC(CCCN1CCN(c2ccccc2)CC1)c1ccccc1
InChIKey: UBEFATOHTBJESS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Binding Assay: 6-week-old Sprague-Dawley (SD) rats were anesthetized in an ether container for 5 minutes, brains were separated from rats, and cortical regions were then separated from the brains of the rats. The cortical regions of the rats were put into a Tris-HCl buffer solution (50 mM, pH 7.7) and homogenized, and the homogenate was centrifuged twice at 4 C. at a rotary speed of 50,000 g to obtain a precipitate (membrane protein). The precipitate was put into a buffer solution, and homogenized, which was used later as a protein source. 0.5 nM [3H]-Ketanserin was used as a radioactive isotope, and 10 uM serotonin was used to remove non-specific bindings. 25 ul of the compound, 100 ul of an aqueous radioactive isotope solution, and 100 ul of the protein source were put together, and kept at 25 C. for 1 hour. The resulting mixture was filtered with a membrane filter in a 96-well harvester when the 96-well plate reaction was completed.
Measurement: IC50 = 514 nM (pChEMBL 6.289999961853027)
Descriptors: MW 353.47, ALogP 3.43, HBA 4, HBD 1, PSA 58.8, QED 0.83
Compound (SMILES): COc1ccccc1N1CCN(CCCC(OC(N)=O)c2ccccc2)CC1
InChIKey: TXRPUILYQGZJMX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Binding Assay: 6-week-old Sprague-Dawley (SD) rats were anesthetized in an ether container for 5 minutes, brains were separated from rats, and cortical regions were then separated from the brains of the rats. The cortical regions of the rats were put into a Tris-HCl buffer solution (50 mM, pH 7.7) and homogenized, and the homogenate was centrifuged twice at 4 C. at a rotary speed of 50,000 g to obtain a precipitate (membrane protein). The precipitate was put into a buffer solution, and homogenized, which was used later as a protein source. 0.5 nM [3H]-Ketanserin was used as a radioactive isotope, and 10 uM serotonin was used to remove non-specific bindings. 25 ul of the compound, 100 ul of an aqueous radioactive isotope solution, and 100 ul of the protein source were put together, and kept at 25 C. for 1 hour. The resulting mixture was filtered with a membrane filter in a 96-well harvester when the 96-well plate reaction was completed.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 383.49, ALogP 3.43, HBA 5, HBD 1, PSA 68.03, QED 0.76
Compound (SMILES): NC(=O)OC(CCCN1CCN(c2ccccn2)CC1)c1ccccc1
InChIKey: KMPZINBUQUOENH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Binding Assay: 6-week-old Sprague-Dawley (SD) rats were anesthetized in an ether container for 5 minutes, brains were separated from rats, and cortical regions were then separated from the brains of the rats. The cortical regions of the rats were put into a Tris-HCl buffer solution (50 mM, pH 7.7) and homogenized, and the homogenate was centrifuged twice at 4 C. at a rotary speed of 50,000 g to obtain a precipitate (membrane protein). The precipitate was put into a buffer solution, and homogenized, which was used later as a protein source. 0.5 nM [3H]-Ketanserin was used as a radioactive isotope, and 10 uM serotonin was used to remove non-specific bindings. 25 ul of the compound, 100 ul of an aqueous radioactive isotope solution, and 100 ul of the protein source were put together, and kept at 25 C. for 1 hour. The resulting mixture was filtered with a membrane filter in a 96-well harvester when the 96-well plate reaction was completed.
Measurement: IC50 = 3140 nM (pChEMBL 5.5)
Descriptors: MW 354.45, ALogP 2.82, HBA 5, HBD 1, PSA 71.69, QED 0.83
Compound (SMILES): O=c1[nH]c2cc(CN3CCCC3)ccc2c2c1CCCN2
InChIKey: UKEYGRHQVLCOHV-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Enzyme Inhibitory Assay: The activity of the compounds according to the present invention to inhibit the PARP-1 enzyme was examined using a PARP Assay kit (4671-096-K) purchased from Trevigen. The assay was performed following a modified previously reported method by Lee et al [Methods Find, Exp. Clin. Pharmacol., 27, 617-622, 2005].Histone was coated on 384-well plate, which is a small volume PS plate (784101) of Greiner Bio-One, and left at 25 C. for 2 hours. After that, the plate was rinsed four times with PBS (7.5 mM Na2HPO4, 2.5 mM NaH2PO4, 145 mM NaCl, pH 7.4), and in order to prevent non-specific reaction, the Strep-diluent (provided from kit of Trevigen) was added and left at 25 C. for one hour. After one hour, the plate was again rinsed with PBS four times, and the compounds of the Examples in various concentrations were put into reactant containing PARP-1 enzyme (0.12 unit/well), 2x PARP cocktail.
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 283.37, ALogP 2.48, HBA 3, HBD 2, PSA 48.13, QED 0.89