lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(c1cccc(F)c1-n1nccn1)N1C2CCC1C(Nc1ccc(C(F)(F)F)cn1)C2
InChIKey: LWXHAAFJSBPQID-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 446.41, ALogP 3.68, HBA 6, HBD 1, PSA 75.94, QED 0.62
Compound (SMILES): Cc1cccc(C(=O)N2C3CCC2C(Nc2ccc(C(F)(F)F)cn2)C3)c1-n1nccn1
InChIKey: IFGKMPOQNDWNDO-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 442.45, ALogP 3.85, HBA 6, HBD 1, PSA 75.94, QED 0.66
Compound (SMILES): Cc1cccc(C(=O)N2C3CCC2C(Nc2ccc(C(F)(F)F)cn2)C3)c1-c1ncco1
InChIKey: UHZOJHWKZIPNJN-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 442.44, ALogP 4.92, HBA 5, HBD 1, PSA 71.26, QED 0.62
Compound (SMILES): NC(=O)c1cccc2[nH]n(C3CCN(C4CCCC4)CC3)c(=O)c12
InChIKey: OVJIYLSTZRNOLG-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 328.42, ALogP 2.01, HBA 4, HBD 2, PSA 84.12, QED 0.9
Compound (SMILES): Cn1c2cccc(C(N)=O)c2c(=O)n1C1CCN(C2CCCCC2)CC1
InChIKey: XPKUFZAKPWQMOR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 356.47, ALogP 2.41, HBA 5, HBD 1, PSA 73.26, QED 0.92
Compound (SMILES): Cn1c2cccc(C(N)=O)c2c(=O)n1C1CCN(C2CCC(F)(F)CC2)CC1
InChIKey: IMXAAXJRLKLQGB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 392.45, ALogP 2.65, HBA 5, HBD 1, PSA 73.26, QED 0.87
Compound (SMILES): Cn1c2cccc(C(N)=O)c2c(=O)n1C1CCN(C2CCCC2)CC1
InChIKey: NPMKKPKCZJHHCM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 342.44, ALogP 2.02, HBA 5, HBD 1, PSA 73.26, QED 0.93
Compound (SMILES): CN1CCC(n2[nH]c3cccc(C(N)=O)c3c2=O)CC1
InChIKey: SBXCLTZHGFAEGE-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 274.32, ALogP 0.7, HBA 4, HBD 2, PSA 84.12, QED 0.84
Compound (SMILES): Cn1c2cccc(C(N)=O)c2c(=O)n1C1CCNCC1
InChIKey: XCMZWTDSYWVLET-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 274.32, ALogP 0.36, HBA 5, HBD 2, PSA 82.05, QED 0.83
Compound (SMILES): CC(C)N1CCC(n2c(=O)c3c(C(N)=O)cccc3n2C)CC1
InChIKey: QTAAMFZROWGTBV-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 316.41, ALogP 1.48, HBA 5, HBD 1, PSA 73.26, QED 0.93
Compound (SMILES): NC(=O)c1cc(F)cc2[nH]n(C3CCNCC3)c(=O)c12
InChIKey: QSOQCQWTGJEJJX-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Displacement Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps of a) providing a reaction mixture containing: the PARP protein isoform under investigation,a compound of formula (IP). b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, and c) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. Preferably, for the screening method above cited, both the PARP protein and the 5H-phenanthridin-6-one-derived probe of formula (IP) are pre-mixed, or the PARP protein and the test compound are pre-mixed.
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 278.29, ALogP 0.49, HBA 4, HBD 3, PSA 92.91, QED 0.75
Compound (SMILES): Cn1c2cc(F)cc(C(N)=O)c2c(=O)n1C1CCNCC1
InChIKey: LIGDLZRFUNWVFK-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Displacement Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps of a) providing a reaction mixture containing: the PARP protein isoform under investigation,a compound of formula (IP). b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, and c) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. Preferably, for the screening method above cited, both the PARP protein and the 5H-phenanthridin-6-one-derived probe of formula (IP) are pre-mixed, or the PARP protein and the test compound are pre-mixed.
Measurement: Kd < 10 nM (pChEMBL 8)
Descriptors: MW 292.31, ALogP 0.5, HBA 5, HBD 2, PSA 82.05, QED 0.85
Compound (SMILES): Cn1c2cc(F)cc(C(N)=O)c2c(=O)n1C1CCN(C2CCCCC2)CC1
InChIKey: PQXUCBRUEQVEIZ-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Displacement Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps of a) providing a reaction mixture containing: the PARP protein isoform under investigation,a compound of formula (IP). b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, and c) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. Preferably, for the screening method above cited, both the PARP protein and the 5H-phenanthridin-6-one-derived probe of formula (IP) are pre-mixed, or the PARP protein and the test compound are pre-mixed.
Measurement: Kd = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 374.46, ALogP 2.55, HBA 5, HBD 1, PSA 73.26, QED 0.9
Compound (SMILES): NC(=O)c1cc(F)cc2[nH]n(C3CCN(C4CCCCC4)CC3)c(=O)c12
InChIKey: OKBDXGNRRUXLQE-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PAR Assay: Cellular activity of PARP-1 inhibitors was assessed by measuring the inhibition of the hydrogen peroxide induced PAR formation in HeLa cells (ECACC). Cellular PAR levels were measured by immunocytochemistry, and quantified using an ArrayScan vTi instrument (Cellomics Thermo Scientific). Studies were performed as follows: 6000 cells/well were seeded in 96 well plates (Perkin Elmer) in MEM/10% FCS and incubated for 24 hours at 37 C., 5% carbon dioxide. Test compounds were then added at the required concentration for 30 minutes. DNA damage was then induced adding hydrogen peroxide at the concentration of 0.1 mM for 15 minutes. Concentration curves were prepared in MEM/10% FCS from compound stocks in DMSO, and final DMSO concentration was 0.002% (v/v). Duplicate wells for each concentration point were prepared with a typical highest compound concentration of 20 uM and serial dilution 1:3. Plates were dried and fixed adding cold methanol-acetone (70:30) solution for 15 minutes at room temperature.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 360.43, ALogP 2.54, HBA 4, HBD 2, PSA 84.12, QED 0.88
Compound (SMILES): CC1CN(CC(=O)NC2C3CC4CC2CC(C(N)=O)(C4)C3)S(=O)(=O)N(c2c(Cl)cc(Cl)cc2Cl)C1
InChIKey: WMNWSFCMPBLVPL-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P50172
Assay: Inhibition of mouse 11beta-HSD1 expressed in CHOK1 cells using XL665-labeled cortisol as substrate measured after 24 hrs by HTRF assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 563.94, ALogP 3.45, HBA 4, HBD 2, PSA 112.81, QED 0.57
Compound (SMILES): Cc1c(-c2ccccc2)n[nH]c1C(=O)Nc1ccc([C@H]2CNCCO2)cc1
InChIKey: YXMBEECTJRWXGW-GOSISDBHSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Human TAAR1 assay: For the construction of expression plasmids the coding sequences of human TAAR 1 were amplified from genomic DNA essentially as described by Lindemann et al.[14]. The Expand High Fidelity PCR System (Roche Diagnostics) was used with 1.5 mM Mg2+ and purified PCR products were cloned into pCR2.1-TOPO cloning vector (Invitrogen) following the instructions of the manufacturer. PCR products were subcloned into the pIRESneo2 vector (BD Clontech, Palo Alto, Calif.), and expression vectors were sequence verified before introduction in cell lines.HEK293 cells (ATCC # CRL-1573) were cultured essentially as described by Lindemann et al. (2005). For the generation of stably transfected cell lines HEK293 cells were transfected with the pIRESneo2 expression plasmids containing the TAAR coding sequences (described above) with Lipofectamine 2000 (Invitrogen) according to the instructions of the manufacturer, and 24 hrs post transfection the culture medium was supplemented with 1 mg/ml G418 (Sigma, Buchs, Switzerland). After a culture period of about 10 d clones were isolated, expanded and tested for responsiveness to trace amines (all compounds purchased from Sigma) with the cAMP Biotrak Enzyme immunoassay (EIA) System (Amersham) following the non-acetylation EIA procedure provided by the manufacturer. Monoclonal cell lines which displayed a stable EC50 for a culture period of 15 passages were used for all subsequent studies.cAMP measurements were performed as described previously (Revel et al., Proc. Natl. Acad. Sci. USA 2011, 108, 8485-8490). In brief, cells that expressed human TAAR1 were plated on 96-well plates (BIOCOAT 6640; Becton Dickinson, Allschwil, Switzerland) and incubated for 20 h at 37° C. Prior to stimulation of the cells with a broad concentration range of agonists for 30 min at 37° C., the cells were washed with PBS and preincubated with PBS that contained 1 mM 3-isobutyl-1-methylxanthine for 10 min at 37° C. and 5% CO2. Stimulation with 0.2% DMSO was set as the basal level, and the effect of 30 μM β-PEA was set as the maximal response. Subsequently, the cells were lysed, and cAMP assays were performed according to the manufacturer's instructions (cAMP kit; Upstate/Millipore, Schaffhausen, Switzerland). Finally, the plates were read with a luminometer (1420 Multilabel counter; PerkinElmer, Schwerzenbach, Switzerland), and the amount of cAMP was calculated. The results were obtained from at least three independent experiments. Experiments were run in duplicate or triplicate. EC50 values are presented as mean ±standard deviation (in μM).
Measurement: EC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 362.43, ALogP 3.3, HBA 4, HBD 3, PSA 79.04, QED 0.67
Compound (SMILES): CCc1[nH]cc2c1NC1=C(C(=O)CNC1)C2c1cccc(Sc2nc3ccccc3[nH]2)c1
InChIKey: ZDDITUPJXGNNKU-UHFFFAOYSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Radioactive Assay: The capacity to inhibit the kinase activity of the enzyme is estimated by measuring the residual kinase activity of the enzyme in the presence of different concentrations of the test compound (generally from 0.17 to 10 000 nM). A dose-response curve is produced, which allows an IC50 (50% inhibitory concentration) to be determined. The kinase activity is measured by a radioactive assay of the amount of radioactive phosphate (33P) incorporated into a fragment of the protein NuMA (Nuclear Mitotic Apparatus protein) after 30 minutes of incubation at 37Â° C. The test compound is first dissolved at different concentrations in dimethyl sulphoxide (DMS (J). Reaction takes place in the wells of a FlashPlate microtiter plate (Nickel Chelate FlashPlate-96, PerkinElmer). Each well (100 Î¼l) contains 10 nM Aurora A, 500 nM NuMA, 1 Î¼M ATP and 0.2 Î¼Ci ATP-Î³-33P in a buffer of 50 mM Tris-HCl, pH=7.5; 10 mM MgCl2; 50 mM NaCl, 1 mM dithiothreitol. The final percentage of DMSO is 3%.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 441.56, ALogP 4.59, HBA 5, HBD 4, PSA 85.6, QED 0.37
Compound (SMILES): CCOC(=O)c1[nH]cc2c1NC1=C(C(=O)CCC1)[C@@H]2c1ccc(Sc2nc3ccccc3[nH]2)o1
InChIKey: QNOOVTZVMOOSAW-FQEVSTJZSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Radioactive Assay: The capacity to inhibit the kinase activity of the enzyme is estimated by measuring the residual kinase activity of the enzyme in the presence of different concentrations of the test compound (generally from 0.17 to 10 000 nM). A dose-response curve is produced, which allows an IC50 (50% inhibitory concentration) to be determined. The kinase activity is measured by a radioactive assay of the amount of radioactive phosphate (33P) incorporated into a fragment of the protein NuMA (Nuclear Mitotic Apparatus protein) after 30 minutes of incubation at 37Â° C. The test compound is first dissolved at different concentrations in dimethyl sulphoxide (DMS (J). Reaction takes place in the wells of a FlashPlate microtiter plate (Nickel Chelate FlashPlate-96, PerkinElmer). Each well (100 Î¼l) contains 10 nM Aurora A, 500 nM NuMA, 1 Î¼M ATP and 0.2 Î¼Ci ATP-Î³-33P in a buffer of 50 mM Tris-HCl, pH=7.5; 10 mM MgCl2; 50 mM NaCl, 1 mM dithiothreitol. The final percentage of DMSO is 3%.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 474.54, ALogP 5.38, HBA 7, HBD 3, PSA 113.01, QED 0.33
Compound (SMILES): COc1cc(F)ccc1-c1ccnc2[nH]c(C3CCNCC3)cc12
InChIKey: UBVYPGDWOQOPMK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) using FL-Ahx-QSPKKG-CONH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 325.39, ALogP 3.84, HBA 3, HBD 2, PSA 49.94, QED 0.77
Compound (SMILES): COc1cc(F)ccc1-c1ccnc2[nH]c(C3CCN(C)CC3)cc12
InChIKey: MYGCBFRVFDUTBD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 uM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 339.41, ALogP 4.19, HBA 3, HBD 1, PSA 41.15, QED 0.78
Compound (SMILES): CN1Cc2ccccc2C(c2cccs2)C1
InChIKey: HFAXMKVVLFVHBE-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 2450 nM (pChEMBL 5.610000133514404)
Descriptors: MW 229.35, ALogP 3.33, HBA 2, HBD 0, PSA 3.24, QED 0.72
Compound (SMILES): Cc1ccc(C2CN(C)Cc3ccccc32)s1
InChIKey: YTYBDRIOUDWUGR-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 3170 nM (pChEMBL 5.5)
Descriptors: MW 243.38, ALogP 3.63, HBA 2, HBD 0, PSA 3.24, QED 0.74
Compound (SMILES): Cc1ccc(C2CN(C)Cc3ccccc32)o1
InChIKey: NPFSYWQNMCUQFC-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 227.31, ALogP 3.17, HBA 2, HBD 0, PSA 16.38, QED 0.74
Compound (SMILES): COc1ccc(C2CN(C)Cc3ccccc32)cn1
InChIKey: XNBOTHGRHLGURP-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 254.33, ALogP 2.67, HBA 3, HBD 0, PSA 25.36, QED 0.82
Compound (SMILES): COc1cccc2cc(C3CN(C)Cc4ccccc43)oc12
InChIKey: OXERSMRQMIRNOS-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki > 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 293.37, ALogP 4.02, HBA 3, HBD 0, PSA 25.61, QED 0.71
Compound (SMILES): CN1Cc2cc(-c3cccnn3)ccc2C(c2cc3ccccc3s2)C1
InChIKey: KIRDSTWSOYAHOS-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 357.48, ALogP 4.94, HBA 4, HBD 0, PSA 29.02, QED 0.51
Compound (SMILES): CN1Cc2cc(-c3cncnc3)ccc2C(c2cc3ccccc3s2)C1
InChIKey: HAQQTPCJCLWUMT-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 357.48, ALogP 4.94, HBA 4, HBD 0, PSA 29.02, QED 0.51
Compound (SMILES): CN1Cc2cc(CN3CCOCC3)ccc2C(c2cc3ccccc3s2)C1
InChIKey: QMOZFCXYKWWVFV-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 35.4 nM (pChEMBL 7.449999809265137)
Descriptors: MW 378.54, ALogP 4.31, HBA 4, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): COc1c(C2CN(C)Cc3ccccc32)ccc2sccc12
InChIKey: JRMIJYKTHQCXEO-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 24.5 nM (pChEMBL 7.610000133514404)
Descriptors: MW 309.43, ALogP 4.49, HBA 3, HBD 0, PSA 12.47, QED 0.69
Compound (SMILES): COc1c(C2CN(C)Cc3cc(-c4ccc(C)nn4)ccc32)ccc2sccc12
InChIKey: TWKWOGUGCQDBEG-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 58.2 nM (pChEMBL 7.239999771118164)
Descriptors: MW 401.54, ALogP 5.25, HBA 5, HBD 0, PSA 38.25, QED 0.47
Compound (SMILES): CN1Cc2cc(-c3cccnn3)ccc2C(c2ccc3sccc3c2)C1
InChIKey: FHVZRKFXAWGVLU-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 357.48, ALogP 4.94, HBA 4, HBD 0, PSA 29.02, QED 0.51
Compound (SMILES): CN1Cc2cc(-c3cccnn3)ccc2C(c2cc3ccccc3o2)C1
InChIKey: UBPCUEVRWJIHLS-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 341.41, ALogP 4.47, HBA 4, HBD 0, PSA 42.16, QED 0.54
Compound (SMILES): CCN1Cc2ccccc2C(c2ccc3cn[nH]c3c2)C1
InChIKey: ZUZFJRJMEROGCY-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 22.5 nM (pChEMBL 7.650000095367432)
Descriptors: MW 277.37, ALogP 3.53, HBA 2, HBD 1, PSA 31.92, QED 0.78
Compound (SMILES): CN1Cc2ccccc2C(c2ccc3sncc3c2)C1
InChIKey: NUMHOXGZNHJTHF-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: In order to evaluate the relative affinity of the various compounds at the NE, DA and 5HT transporters, HEK293E cell lines were developed to express each of the three human transporters. cDNAs containing the complete coding regions of each transporter were amplified by PCR from human brain libraries. The cDNAs contained in pCRII vectors were sequenced to verify their identity and then subcloned into an Epstein-Barr virus based expression plasmid (Shen et al., Gene 156:235-239 (1995), which is hereby incorporated by reference in its entirety). This plasmid containing the coding sequence for one of the human transporters was transfected into HEK93E cells. Successful transfection was verified by the ability of known reuptake blockers to inhibit the uptake of tritiated NE, DA or 5HT.For binding, cells were homogenized, centrifuged, and then resuspended in incubation buffer (5 mM Tris, 120 mM NaCl, 5 mM KCl, pH 7.4). Then, the appropriate radioligand was added.
Measurement: Ki = 38.6 nM (pChEMBL 7.409999847412109)
Descriptors: MW 280.4, ALogP 3.87, HBA 3, HBD 0, PSA 16.13, QED 0.67
Compound (SMILES): C=CC(=O)N1CC[C@@H](Oc2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)cc3)c(C(N)=O)nc2CC)C1
InChIKey: QKDCLUARMDUUKN-XMMPIXPASA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant in human NCI-H1975 cells assessed as suppression of cell proliferation
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 562.72, ALogP 2.26, HBA 9, HBD 2, PSA 120.16, QED 0.44
Compound (SMILES): Oc1ccc(-c2nsc(-c3ccc(O)c(O)c3)n2)cc1O
InChIKey: MKKIWISQFSVGQX-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Thio S Fluorometry Assay: The Thio S fluorometry assay as a primary screening method to identify tau protein aggregation inhibitors from our small molecule library. Aggregated tau fibrils were prepared in the presence of equimolar ratios of TauRD and heparin (10 μM each) in 20 mM Na-phosphate buffer, pH7.4. The reaction mixture was incubated at 37° C. with shaking (800-1000 rpm) for 22-24 hr (or for 3 days). In the Thio S inhibition assays, test compounds at 0, 0.1, 1, 10 and 100 μM were added at time 0 into the reaction containing TauRD and heparin. The same reaction mixture (+/− increasing concentrations of compounds) but without TauRD were also set up in parallel to serve as background controls. For all test compounds background fluorescence readings were very low, usually <5% of those of the TauRD-containing wells. For each compound, the IC50 was calculated using Prism version 5 software (GraphPad Software) by nonlinear regression [(Log [inhibitor] vs. normalized response; variable slope)].
Measurement: IC50 = 10240 nM (pChEMBL 4.989999771118164)
Descriptors: MW 302.31, ALogP 2.69, HBA 7, HBD 4, PSA 106.7, QED 0.54
Compound (SMILES): CC(C)CNC(=O)C(NCC(O)C(Cc1ccccc1)NC(=O)c1cccc(C(=O)N(C)C(C)c2ccccc2)c1)C(C)O
InChIKey: RLSADXVPOTXGOV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: Previously, one of the following compounds discussed below have been studied in memapsin 2 inhibition (Ghosh et al., 2008), which the others are previously unpublished. Given the closely related substrate specificity for memapsin 1 and memapsin 2, the inventors chose to screen these previously identified memapsin 2 inhibitors for lead compounds as memapsin 1 inhibitors. Recombinant memapsin 1 ectodomain was prepared as described by Turner et al. (2002) and assayed using a commercially purchased fluorescent substrate.
Measurement: Ki = 5812 nM (pChEMBL 5.239999771118164)
Descriptors: MW 602.78, ALogP 3.33, HBA 6, HBD 5, PSA 131, QED 0.18
Compound (SMILES): CCCC(O)C(NCC(O)C(Cc1ccccc1)NC(=O)c1cccc(C(=O)N2CCCC2OC)c1)C(=O)NCC(C)C
InChIKey: JICMITPNTOPAGH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: Previously, one of the following compounds discussed below have been studied in memapsin 2 inhibition (Ghosh et al., 2008), which the others are previously unpublished. Given the closely related substrate specificity for memapsin 1 and memapsin 2, the inventors chose to screen these previously identified memapsin 2 inhibitors for lead compounds as memapsin 1 inhibitors. Recombinant memapsin 1 ectodomain was prepared as described by Turner et al. (2002) and assayed using a commercially purchased fluorescent substrate.
Measurement: Ki = 267 nM (pChEMBL 6.570000171661377)
Descriptors: MW 596.77, ALogP 2.49, HBA 7, HBD 5, PSA 140.23, QED 0.2