lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(O)c1ccc(Nc2ncnc3c2CCN(c2ccc(C#N)c(Cl)c2)C3)nc1
InChIKey: TYOPGJVWUJIKHX-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist Activity for AR: Antagonist activity for AR was evaluated according to the following method. COS-7 cells (ATCC) were transfected with pMMTV-luc vector (reporter plasmid having, as an androgen response element, murine mouse mammary virus long terminal repeat) and pEX-hAR vector (human androgen receptor expression vector: which expresses human AR gene under control of CMV promoter) by using Nucleofector (registered trademark) Kit R (Lonza) as a transfection reagent and Amaxa (Lonza). The COS-7 cells obtained after transfection were seeded in a clear bottom 96 well microplate (BD) at 1.5×104/well with phenol red free RPMI1640 containing 10% charcoal-treated fetal bovine serum (hereinbelow, DCC-FBS) (hereinbelow, the medium is referred to as an evaluation medium), and then cultured overnight. The culture was added with the evaluation medium containing dihydrotestosterone (DHT) (final concentration of DHT: 1 nmol/L) or the evaluation medium containing the compound of Examples or the compound of Comparative Examples (final concentration of the compound of Examples or the compound of Comparative Examples: 5, 14, 41, 123, 370, 1111, 3333, or 10000 nmol/L), followed by culture for 24 hours. Then, the transcription activity value was measured. The transcription activity was measured by using Bright-Glo Luciferase Assay System (Promega). From the measured transcription activity, 50% transcription activity inhibition concentration (IC50 value) was calculated by logistic regression when the transcription activity value obtained by using 1 nmol/L DHT was 100% and the transcription activity value obtained by using the evaluation medium only was 0%.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 420.9, ALogP 3.93, HBA 7, HBD 2, PSA 97.96, QED 0.66
Compound (SMILES): CC(C)(C(=O)N1CCOc2c(C#N)cncc2C1)C(F)F
InChIKey: CSCLQCHKUAMZOY-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Fluorescent Polarization Binding (FP Binding) Assay: Test compounds were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final). In each well of a 384-well Plate were dispensed 0.1 μL of compound solution (or DMSO for controls) followed by 5 μL of GST-hRIPK1 (8-327) at twice the final concentrations in assay buffer (50 mM HEPES pH 7.5, 10 mM NaCl, 50 mM MgCl2, 0.02% CHAPS, 0.5 mM DTT and 0.01% Pluronic F127). For negative control the enzyme addition was replaced by assay buffer only.After addition of 5 μL of fluorescentlabeled ligand at twice the final concentrations in assay buffer, the plate was incubated at RT for 30 mM. At the end, the binding was measured as FP value with the Envision (PerkinElmer) plate reader using filter for an excitation λ=531 nm FP and an emission λ=595 nm FP (S & P-pol). GST-hRIPK1 (8-327) enzyme was produced via Baculovirus expression.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 295.29, ALogP 1.97, HBA 4, HBD 0, PSA 66.22, QED 0.84
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cncc(-c3oncc3C)c2)n1
InChIKey: ADGOPPKEIZXKAZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Assay: Kinase base buffer (50 mM HEPES, pH 7.5 0.0015% Brij-35; 10 mM MgCl2 2 mM DTT) and Stop buffer, (100 mM HEPES, pH 7.5 0.015% Brij-35; 0.2% Coating Reagent (50 mM EDTA) are prepared. Test compound is diluted in 100% DMSO to 50-times the desired final inhibitor concentration (the Stock Solution) and serially diluted in half-log increments resulting in final concentrations 250 μM to 75 μM, 25 μM, 7.5 μM, 2.5 μM, 0.75 μM, 0.25 μM, 75 nM, 25 nM, 7.5 nM in DMSO. 10 μl of each compound is placed in a 96-well plate as the intermediate plate. 90 μl of Kinase Buffer is added to to each well to prepare the intermediate plate.Figure US10906896-20210202-P00001Mix the compounds in intermediate plate for 10 min on shaker. For the assay of enzyme inhibitions, 5 μl of each well from the intermediate plate is transferred to a 384-well plate in duplicates, 10. Then 10 μl of 2.5× enzyme solution is added to each well of the 384-well assay plate and incubated for 10 min. Then enzyme substrate is added as 10 μl of 2.5×FAM-labeled peptide+ATP solution to each well of the 384-well assay plate. The reaction is allowed to proceed at 28° C. and quenched with the addition of 25 μl of stop buffer.
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 574.69, ALogP 5.55, HBA 9, HBD 2, PSA 112.31, QED 0.25
Compound (SMILES): N#CC[C@H](C1CCCC1)n1cc(-c2ncnc3[nH]ccc23)c(N)n1
InChIKey: ZGENDZDSLYKCSI-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzymatic Activity Assay: A testing platform for kinase activity of JAK2 (wild type and V617F mutant type) was established based on Homogeneous Time-Resolved Fluorescence (HTRF) assay, and the activities of the compounds were tested using the platform. The compounds were subjected to three-fold gradient dilutions with 100% DMSO with a starting concentration of 1 mM (11 dilutions in total). 4 μL of each dilution was added to 96 μL of reaction buffer (50 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 0.005% BAS, 2 mM DTT) and mixed homogeneously. 2.5 μL of the resulting liquid was then added to a 384-well plate (OptiPlate-384, available from PerkinElmer), and then 5 μL of JAK2 kinase (available from Carna) was added. The mixture was mixed homogeneously by centrifugation. Then 2.5 μL of a mixture of ATP (the final concentration is the corresponding Km value) and TK peptide (HTRF KinEASE-TK, available from Cisbio) was added to initiate the reaction (the total reaction volumn is 10 μL). The 384-well plate was placed in an incubator and the reaction was allowed to conduct for 120 min at 23° C. Then the reaction was terminated by adding 5 μL of Eu3+ cryptate-labled anti-phosphotyrosine antibody (available from Cisbio), and 5 μL of Streptavidin-XL-665 (HTRF KinEASE-TK, available from Cisbio). The plate was incubated in the incubator for 1 hr, and then the fluorescence values were read on Envision (available from PerkinElmer). The excitation wavelength was 320 nm, and the emission wavelengths for detecton were 665 nm and 620 nm. The enzymatic activity was representd by a ratio of the two readout at the two emission wavelengths.
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 321.39, ALogP 3.05, HBA 6, HBD 2, PSA 109.2, QED 0.77
Compound (SMILES): CC(C)c1ccc(N(C)c2ccc3c(c2)OCC[C@H]3CNc2cnccc2C(=O)O)cc1
InChIKey: NDVITLLKZQXKGU-IBGZPJMESA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 431.54, ALogP 5.65, HBA 5, HBD 2, PSA 74.69, QED 0.5
Compound (SMILES): CCn1ncc2c1-c1cnc(N)c(c1)O[C@H](C)c1cc(F)ccc1-c1nn(C)nc1C2
InChIKey: DTWUUAFTYSMNQX-GFCCVEGCSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of wild type ROS1 (unknown origin)
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 419.46, ALogP 3.53, HBA 8, HBD 1, PSA 96.67, QED 0.51
Compound (SMILES): C=CC(=O)NC1CCN(c2ncc3ncnc(Nc4ccc(Oc5ccc6c(c5)ncn6C)c(C)c4)c3n2)CC1
InChIKey: YSGNGFPNTLERCR-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 535.61, ALogP 4.42, HBA 10, HBD 2, PSA 122.98, QED 0.29
Compound (SMILES): C[C@H]1CN2CCNCc3ccc(C(=O)NCC(F)F)c1c32
InChIKey: KGOOOHQKLRUVSF-VIFPVBQESA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-DOI from 5-HT2C receptor (unknown origin) expressed in HEK293 cell membrane incubated for 1 hr by scintillation counter analysis
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 295.33, ALogP 1.71, HBA 3, HBD 2, PSA 44.37, QED 0.89
Compound (SMILES): Cn1c(-c2ccc(C(N)=O)cc2F)nnc1C(C)(C)Oc1c(F)cc(Cl)cc1F
InChIKey: CMQOKZCYVZFZLZ-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16232
Assay: Inhibition Assay: The procedure for measuring the 11β-HSD1-inhibitory activity is as follows. The enzyme reaction and the measurement were carried out using a 384-well plate. The enzyme was prepared in accordance with Journal of Biological Chemistry, 2001, Vol. 276, p. 21343-21350. The reaction was carried out by adding a test compound at various concentrations to a reaction liquid consisting of a 5 mM phosphate buffer (pH 6.6), 200 nM cortisone, 40 μM reduced nicotinamide adenine dinucleotide phosphate (NADPH), and rat recombinant 11β-HSD1, followed by incubating at room temperature for one hour (10 μl/well). The test compound was prepared by dissolving in dimethyl sulfoxide (DMSO) such that a DMSO concentration reached 1% in the reaction liquid. After the enzyme reaction was completed, the enzyme inhibitory action was measured by detecting cortisol using a homogeneous time-resolved fluorescence (HTRF) method. Each of a d2-labeled cortisol containing 400 μM carbenoxolone and a cryptate-labeled cortisol antibody (CIS Bio International Co., Ltd.) was added at 5 μl/well, followed by incubating at room temperature for 2 hours, and then the fluorescence intensity was measured using a fluorophotometer (trade name: ARVO HTS 1420, Perkin Elmer/Wallac), and the enzyme inhibitory activity was calculated from the fluorescence intensity ratio of two wavelengths (665 nm/620 nm).The measurement results were calculated by averaging the values of 3 wells of the same condition. The ratio when DMSO was added instead of the test compound was taken as 0% and the ratio when 11β-HSD1 was not added was taken as 100%, thereby calculating the 50% inhibition concentration of the test compound as IC50 of the compound inhibitory activity.
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 424.81, ALogP 3.97, HBA 5, HBD 1, PSA 83.03, QED 0.67
Compound (SMILES): C=CC(=O)N1CCN(c2c(C#N)c(=O)n(-c3c(C)ccnc3C(C)C)c3nc(-c4c(N)c(F)c(F)c(F)c4F)c(Cl)cc23)CC1
InChIKey: QRRJEUIQLZNPIO-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of His-tagged GDP-loaded KRAS G12C mutant (unknown origin) assessed as SOS1-mediated guanine nucleotide exchange preincubated with compound for 1 hrs followed by Flag-tagged SOS1 ExD and GTP addition and measured after 4 hrs by TR-FRET assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 640.04, ALogP 5.38, HBA 8, HBD 1, PSA 121.14, QED 0.1
Compound (SMILES): N#Cc1cc(F)cc(Oc2ccc3c4c2[C@@H](F)C[C@]4(O)C(F)(F)C3(F)F)c1
InChIKey: ZIEZRTWLAIDXDH-BLLLJJGKSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: VEGF ELISA Assay: The ability of the disclosed compounds to inhibit HIF-2α was measured by determining VEGF expression in 786-O cells. About 7500 786-O cells were seeded into each well of a 96-well, white, clear bottom plate (07-200-566, Fisher Scientific) with 200 ul growth medium. Four hours later, compounds were dispensed into wells by Tecan D300e digital dispenser with starting concentration of 10 uM and ½ log of dilution down to 1 nM as final concentration. Each concentration of treatment was performed in duplicate. About 20 hours later, medium was removed and fresh medium was added, followed by compounds treatment as described above. 24 hours later, cell culture medium was collected to determine VEGF concentration using an ELISA kit (R&D systems, cat #DVE00) following the manufacturer's instruction.The EC50 is calculated by GraphPad Prism using the dose-response-inhibition (four parameter) equation. The plate with cells was then subjected to CellTiter-Glo luminescence cell viability assay (Promega) to determine the effect of these compounds on cell numbers after the above treatment.
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 385.26, ALogP 4.83, HBA 3, HBD 1, PSA 53.25, QED 0.75
Compound (SMILES): C[C@@H]1CN(c2cc(N3CCN(CC4=C(c5ccc(Cl)cc5)CC(C)(C)CC4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c2cc3cc[nH]c3nc2O1
InChIKey: CCDRQWAEZGRMTP-WJOKGBTCSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 923.54, ALogP 8.79, HBA 12, HBD 3, PSA 175.27, QED 0.08
Compound (SMILES): COc1cc(N[C@H](C(=O)c2c[nH]c3ccc(OC(F)(F)F)cc23)c2ccc(Cl)cc2OC)cc(S(C)(=O)=O)c1
InChIKey: QNOPDDHSGQQLCV-DEOSSOPVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG stably expressed in CHO cells by automated Qpatch electrophysiological assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 582.98, ALogP 6.18, HBA 7, HBD 2, PSA 106.72, QED 0.23
Compound (SMILES): Cc1nc(NC(=O)N2CCC(C)(C)C2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: NXFPMDWYDKHFMM-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of KIT (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 = 76.98 nM (pChEMBL 7.110000133514404)
Descriptors: MW 420.47, ALogP 3.77, HBA 7, HBD 1, PSA 102.24, QED 0.69
Compound (SMILES): C=CC(=O)N1C[C@@H](n2nc(C#Cc3c(F)cc4c(ncn4C4CC4)c3F)c(C(N)=O)c2NC)C[C@@H]1COC
InChIKey: YXVDEILMUVTDMK-JKSUJKDBSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of wild type FGFR1 (unknown origin) using 5-FAM-KKKKEEIYFFF-CONH2 peptide as fluorogenic substrate incubated for 80 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 523.54, ALogP 2.36, HBA 8, HBD 2, PSA 120.3, QED 0.36
Compound (SMILES): COc1ccc2cc(O)c(N3CC(=O)NS3(=O)=O)c(F)c2c1
InChIKey: CPLSFGHDGOFDRP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of His-tagged PTPN2 (unknown origin) by mobility shift assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 326.31, ALogP 0.87, HBA 5, HBD 2, PSA 95.94, QED 0.85
Compound (SMILES): CN1CCC[C@]1(C)/C=C/S(=O)(=O)NC(=O)Nc1c2c(cc3c1CCC3)CCC2
InChIKey: HAMGPBKPACGWND-ZOXUKVPXSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in LPS/ATP induced IL-1beta production preincubated with LPS for 4 hrs prior to compound addition for 30 mins followed by ATP treatment for 1 hr
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 403.55, ALogP 3.11, HBA 4, HBD 2, PSA 78.51, QED 0.81
Compound (SMILES): CCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CN(CC(=O)O)CC(F)(F)F)cc1OC
InChIKey: XWGKZKKNJOQUSG-SFHVURJKSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Human TLR7 Assay: Recombinant human TLR7 was stably expressed in a HEK293 cell line already stably expressing the pNiFty2-SEAP reporter plasmid; integration of the reporter gene was maintained by selection with the antibiotic zeocin. The most common variant sequence of human TLR7 (represented by the EMBL sequence AF240467) was cloned into the mammalian cell expression vector pUNO and transfected into this reporter cell-line. Transfectants with stable expression were selected using the antibiotic blasticidin. In this reporter cell-line, expression of secreted alkaline phosphatase (SEAP) is controlled by an NFkB/ELAM-1 composite promoter comprising five NFkB sites combined with the proximal ELAM-1 promoter. TLR signaling leads to the translocation of NFkB and activation of the promoter results in expression of the SEAP gene. TLR7-specific activation was assessed by determining the level of SEAP produced following overnight incubation of the cells at 37° C. with the standard compound in the presence of 0.1% (v/v) dimethylsulfoxide (DMSO). Concentration dependent induction of SEAP production by compounds was expressed as the concentration of compound which produced half of the maximal level of SEAP induction for that compound (EC50). TLR7 activity for compounds of the present disclosure was assessed using the human TLR7 assay.
Measurement: EC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 513.56, ALogP 3.38, HBA 8, HBD 4, PSA 133.83, QED 0.3
Compound (SMILES): C=C(C)C(=O)Nc1ccc(-c2c(-c3ccc(Oc4nccc(C)n4)c(F)c3)c3c(N)ncnc3n2C)cc1
InChIKey: XOQVZSSDIQQUGO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin)
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 509.55, ALogP 5.43, HBA 8, HBD 2, PSA 120.84, QED 0.29
Compound (SMILES): Cc1cc(C)c2c(n1)CN(C(=O)CC1CN(c3ccnc(C(F)(F)F)c3)C1)C2
InChIKey: DTCZNKWBDTXEBS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human muscarinic M4 receptor expressed in HEK293 cells in presence of EC20 concentration of acetylcholine by Glosensor cAMP assay
Measurement: EC50 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 390.41, ALogP 3.48, HBA 4, HBD 0, PSA 49.33, QED 0.81
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(Nc3cc(Cl)c(F)cc3C(C)(C)O)n2)c(OC)cc1N1CC[C@@H](N(C)C)C1
InChIKey: BTMKEDDEMKKSEF-QGZVFWFLSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR D770_N771insSVD mutant (unknown origin) expressed in human NCI-H2073 cells preincubated for 2 hrs followed by EGF stimulation for 10 mins by HTRF assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 584.1, ALogP 5.26, HBA 9, HBD 4, PSA 114.88, QED 0.24
Compound (SMILES): N#C[C@H](C[C@@H]1CCCNC1=O)NC(=O)[C@H](CC1CC1)NC(=O)c1cc2cccc(Cl)c2[nH]1
InChIKey: BNMFQWUHWYJTRI-BQFCYCMXSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3-chymotrypsin-like protease assessed as inhibition constant
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 455.95, ALogP 2.64, HBA 4, HBD 4, PSA 126.88, QED 0.49
Compound (SMILES): C[C@@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1C[C@@H]2C[C@]2(c2cc(C(F)(F)F)on2)C1)C(F)(F)F
InChIKey: MYHDQTVHHMSLEF-DDBGAENHSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Affinity On-target Cellular interaction: (Inhibition of radiolabelled [3H]glycine uptake in human SK-N-MC cells) EUB0002599a SLC6A9
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 512.43, ALogP 3.84, HBA 6, HBD 0, PSA 89.71, QED 0.57
Compound (SMILES): Nc1ncc(-c2ccc([C@@]34C[C@@H]3CN(C3CCOCC3)C4)cc2)cc1C(=O)NC12CCC(O)(CC1)CC2
InChIKey: KPRPFTOLWQQUAV-OCVAFRRMSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Caliper Assay: A kinase selectivity panel which measures substrate peptide phosphorylation was set-up for wild-type ALK2 (aa172-499), ALK2 FOP mutant (aa172-499 R206H), ALK1 (aa166-493), ALK5 (aa162-503) and ALK6 (aa168-495). The technology used for the described assay is based on the separation and quantification of substrate and product in an electrical field. In the course of the kinase reaction the peptide substrate is phosphorylated by a kinase. The transfer of a phosphate residue also causes the introduction of two additional negative charges and hence to a change in the net charge of the phospho-peptide compared to the unphosphorylated peptide. Due to this difference in charge the phosphorylated und unphosphorylated peptides migrate with different velocities in an electrical field.In the applied method, this separation takes place inside a chip that contains a complex capillary system for simultaneous analysis of 12 samples (12-sipper chip, Caliper Technologies Corp., Mountain View, USA). In order to allow the detection and quantification of the peptides in the capillary system, the peptides carry a fluorescent label (fluorescein). With this label the peptides can be quantified by fluorescence intensity through the instruments laser and detection system (LC3000, Caliper Life Sciences).The assays were performed in 384-well, low volume microtiter assay plates in a final reaction volume of 9 ul. Dose-response curves were generated by incubating 10 nM of each kinase together with 2 μm of the fluorescently labeled substrate peptide 5-Fluo-Ahx-KKYQAEEN-T-YDEYENKK-amid (10 mM stock solution in DMSO) in 50 mM Hepes pH 7.5, 0.02% Tween 20, 0.02% BSA, 1 mM DTT, 10 m Na3VO4, 10 mM If-Glycerolphosphate, 1 mM MgCl2, 12 mM MnCl2 (ALK1 and ALK6 7 mM) and 15 μm ATP for 60 min at 30° C. in the presence or absence of compound diluted in DMSO. Kinase reaction were terminated by adding 15 ul STOP buffer (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35.Plates with terminated kinase reactions were transferred to the Caliper LC3000 workstation (Caliper Technologies Corp., Mountain View, USA) for reading. The relative amount of phosphorylated peptide r, was calculated using the heights of the substrate peak, s, and the product peak, p: r=p/(p+s).
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 502.66, ALogP 3.65, HBA 6, HBD 3, PSA 100.71, QED 0.58
Compound (SMILES): CC(C)[C@H](N)C(=O)SCC/C=C/[C@@H]1CC(=O)NCc2nc(cs2)C(=O)NC(C)(C)C(=O)N[C@@H](C(C)C)C(=O)O1.O=S(=O)(O)c1ccccc1
InChIKey: NIRZCQHSBOSBOH-CVYLVPDPSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using ZMAL (Z-(Ac)Lys-AMC) as fluorogenic substrate preincubated for 5 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 581.76, ALogP 1.91, HBA 10, HBD 4, PSA 169.58, QED 0.21
Compound (SMILES): C[C@@H](NC(=O)N1C(=O)[C@H](Cc2ccnc(N)c2)[C@H]1C(=O)O)C1CCCCC1
InChIKey: NYPSZHLKEMYZKK-XFJVYGCCSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human FXIa
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 374.44, ALogP 1.8, HBA 5, HBD 3, PSA 125.62, QED 0.67
Compound (SMILES): CCOCc1cnc(Cl)nc1Oc1ccc2c(ccc3sc4c(c32)NC[C@@H](C)NC4=O)n1
InChIKey: PYOQIOLRFIRRSO-LLVKDONJSA-N
Target: MAP kinase-activated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49137
Assay: Inhibition of human MK2 recombinant assessed as phosphorylation of Sox peptide by continuous fluorescence read assay
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 469.95, ALogP 4.77, HBA 8, HBD 2, PSA 98.26, QED 0.41
Compound (SMILES): C[C@]1(c2ccc(Cl)cn2)Oc2cccc(C3CCN(Cc4nc5ccc(C(=O)O)cc5n4C[C@@H]4CCO4)CC3)c2O1
InChIKey: SVPYZAJTWFQTSM-UGDMGKLASA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in HEK293 cells coexpressing CRE LUC incubated for 5 hrs by luciferase based microplate reader analysis
Measurement: EC50 = 9.23 nM (pChEMBL 8.039999961853027)
Descriptors: MW 575.07, ALogP 5.6, HBA 8, HBD 1, PSA 98.94, QED 0.3
Compound (SMILES): CC(C)NC(=O)c1ccc2c(c1)[C@]1(CCO2)C[C@H]1C(=O)Nc1cc(C#N)ccc1CCCC(=O)O
InChIKey: QSRLBYGDVFRMPT-IDISGSTGSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: EP4 Antagonistic Activity Measurement: EP4 Antagonistic Activity Measurement Experiment Using Prostanoid Receptor Subtype Expressing CellsCHO cells expressing rat EP4 receptor subtypes were prepared according to the methods of Nishigaki et al. (FEBS Letters, Vol. 364, p. 339-341, 1995), and used for experiment. Cultured subconfluent cells were detached, and suspended in an assay medium (MEM containing 1 mmol/L IBMX, 1% HSA) in a concentration of 1×106 cells/mL. For reaction, PGE2 was added to the cell suspension (25 μL) in a final concentration of 10 nmol/L, either alone or as a 25-μL PGE2 solution containing the test compound. After 30 minutes of reaction at room temperature, the amount of cAMP in the cells was quantified according to the method in the descriptions of the cAMP assay kit (CISBIO).The antagonistic effect (IC50 value) of the test compound was calculated as a value that represents an inhibition rate against a reaction with PGE2 alone at 10 nM, a concentration that produces a submaximal cAMP producing effect.
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 475.55, ALogP 3.78, HBA 5, HBD 3, PSA 128.52, QED 0.53
Compound (SMILES): C=C1C[C@@H]2CC[C@H]1[C@@H](C(=O)N1CCC3(CC1)CN(c1ncncc1Oc1ccc(F)cc1C(=O)N(C(C)C)C(C)C)C3)N2
InChIKey: JQHJEDMMWUIYCE-FVVBACEJSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Test for Evaluating the Inhibition of the Menin-MLL Binding: Menin1-615 wherein 6×His tag and HA tag are inserted in the N-terminus, and myc tag is inserted in the C-terminus (hereinafter, referred to as His-Menin1-615), is diluted with an assay buffer (25 mmol/L HEPES, 150 mmol/L NaCl, 1 mmol/L dithiothreitol, 0.5% (w/v) Tween 80, 0.3% (w/v) BSA, 0.3% (w/v) skim milk) to adjust the final concentration to 30 nmol/L. The test compounds are also diluted with the assay buffer to adjust each concentration of the test compounds to 0.005 to 5 μmol/L. The prepared His-Menin1-615 and test compounds were added to a light-shielding 384-well low-volume plate (Corning, #4514) in 2 μL/well and 6 μL/well, respectively, and the plate was covered with a lid for light-shielding (Corning, #3935), and incubated at room temperature for 3 hours. After the incubation, MLL1-172 wherein FLAG tag is inserted in the C-terminus (MLL1-172-FLAG), was separately diluted with the assay buffer to adjust the final concentration to 50 nmol/L. The prepared MLL1_172-FLAG was added to the above plate in 2 μL/well, and the plate was covered with a lid for light-shielding and incubated at room temperature for an hour.Then, anti-6HIS-d2 antibody (cisbio, 61HISDLA) and anti-FLAGM2-K antibody (cisbio, 61FG2KLA) were diluted with an antibody dilution buffer (50 mmol/L Tris, 150 mmnol/L NaCl, 800 mmnol/L KF, pH 7.4) to adjust the final concentration to 1.4 μg/mL to prepare an antibody mixture. The prepared antibody mixture was added to the above plate in 10 μL/well, and the plate was covered with a lid and incubated at 4° C. for 17 to 24 hours. After the incubation, the signal was detected with RUBYstar (BMG LABTECH). The binding inhibition rate (%) at each concentration of the test compounds was calculated from the following formula, and the IC50 value was obtained, that corresponds to the concentration of the test compound at which the binding inhibition rate is 50%.Binding inhibition rate (%)={1−(A−C)/(B−C)}×100A: Signal in the presence of test compoundB: Signal of negative control (in the absence of test compound)C: Signal of positive control (in the presence of known compound at the concentration which shows 100% inhibition ratio).
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 590.74, ALogP 4.79, HBA 7, HBD 1, PSA 90.9, QED 0.46
Compound (SMILES): Cn1cc(-c2ccc(CNc3cc(-c4cnc5cc(OCCCN6CCCC6)ccn45)ncn3)cc2)cn1
InChIKey: LVMAULGVWBINFP-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of KIT (delta 560 to 576 residues) deletion/V654A double mutant autophosphorylation at Y703 in human GIST-430/654 harboring KIT (delta560 to 576 residues) deletion mutation and V654A point mutation incubated for 45 mins by Luminex-based bead assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 508.63, ALogP 4.67, HBA 9, HBD 1, PSA 85.4, QED 0.27
Compound (SMILES): Br.O=C(NO)c1ccc(Cn2cc(CN[C@@H]3C[C@H]3c3ccccc3)cn2)cc1
InChIKey: VYVGGNXALTUECS-CMXBXVFLSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 362.43, ALogP 2.7, HBA 5, HBD 3, PSA 79.18, QED 0.45
Compound (SMILES): C=CC(=O)N[C@H]1CCC[C@H]1NC(=O)c1sc2nccc3c2c1NC(=O)N3c1cnc(CC(C)C)cc1C
InChIKey: OPLNLPWGEZNZFL-ZWKOTPCHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Lanthascreen Binding Assay: A BTK kinase lanthascreen binding assay monitors compound binding to unphosphorylated-BTK kinase domain (UP-BTK), by competing with a fluorescent labeled tracer. UP-BTK, consisting of the kinase domain of non-phosphorylated BTK protein (389-659aa), was produced in a Baculovirus/insect cell expression system. Into a 384-well plate, 2 ng of GST-tagged human BTK (389-659aa) was incubated with compound, 50 nM of Tracer 236 and 2 nM anti-GST antibody for 60 minutes using an optimized Lanthascreen assay. After 60 minutes, plates were read at 340 nM and 615/665 nM in an Infinite F500 (Tecan).
Measurement: IC50 = 8.13 nM (pChEMBL 8.09000015258789)
Descriptors: MW 518.64, ALogP 4.83, HBA 6, HBD 3, PSA 116.32, QED 0.39
Compound (SMILES): Cc1cc(OCCCNCC(C)(C)C(N)=O)ccc1Cc1c(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)n[nH]c1C(C)C
InChIKey: LREHMKLEOJAVMQ-TXKDOCKMSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Affinity On-target Cellular interaction: (Inhibition of radiolabelled [14C]AMG uptake by COS-7 cells expressing SLC5A1) EUB0002638a SLC5A1
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 564.68, ALogP 0.48, HBA 10, HBD 7, PSA 192.41, QED 0.16
Compound (SMILES): Cc1ccc([C@H]2C[C@@H]2COc2cc(NCc3nnc(C)s3)nc(C)n2)nc1
InChIKey: WQKPZDLZRFTMTI-CABCVRRESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of human PDE10A2 transfected in human AD293 cells cytosolic fraction using cAMP as substrate by fluorescence polarization assay
Measurement: Ki = 0.029 nM (pChEMBL 10.539999961853027)
Descriptors: MW 382.49, ALogP 3.44, HBA 8, HBD 1, PSA 85.71, QED 0.67
Compound (SMILES): CO[C@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@H]([C@H](C)C[C@@H]2CC[C@@H](OC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)N3CCc4cc(Cn5nc(-c6ccc7oc(N)nc7c6)c6c(N)ncnc65)ccc4C3)[C@H](OC)C2)C[C@@H](O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C/1C
InChIKey: IUTYTXDIGUNPAA-GKVGALOGSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay
Measurement: IC50 = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 1778.16
Compound (SMILES): Cn1cncc1-c1c(F)cncc1NC(=O)c1c(N)nn2cc(F)cnc12
InChIKey: RBQPCTBFIPVIJN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition Assay: Compounds were screened for their ability to inhibit ATR kinase using a radioactive-phosphate incorporation assay. Assays were carried out in a mixture of 50 mM Tris/HCl (pH 7.5), 10 mM MgCl2 and 1 mM DTT. Final substrate concentrations were 10 μM [γ-33P]ATP (3mCi 33P ATP/mmol ATP, Perkin Elmer) and 800 μM target peptide (ASELPASQPQPFSAKKK) (SEQ ID NO:1).Assays were carried out at 25° C. in the presence of 5 nM full-length ATR. An assay stock buffer solution was prepared containing all of the reagents listed above, with the exception of ATP and the test compound of interest. 13.5 μL of the stock solution was placed in a 96 well plate followed by addition of 2 μL of DMSO stock containing serial dilutions of the test compound (typically starting from a final concentration of 15 μM with 3-fold serial dilutions) in duplicate (final DMSO concentration 7%). The plate was pre-incubated for 10 minutes at 25° C. and the reaction initiated by addition of 15 μL [γ-33P]ATP (final concentration 10 μM).The reaction was stopped after 24 hours by the addition of 30 μL 0.1M phosphoric acid containing 2 mM ATP. A multiscreen phosphocellulose filter 96-well plate (Millipore, Cat no. MAPHN0B50) was pretreated with 100 μL 0.2M phosphoric acid prior to the addition of 454 of the stopped assay mixture. The plate was washed with 5×200 μL 0.2M phosphoric acid. After drying, 100 μL Optiphase SuperMix liquid scintillation cocktail (Perkin Elmer) was added to the well prior to scintillation counting (1450 Microbeta Liquid Scintillation Counter, Wallac).
Measurement: Ki = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 370.32, ALogP 1.64, HBA 8, HBD 2, PSA 116.02, QED 0.57
Compound (SMILES): C[C@@H](O)[C@@H](C(N)=O)N1C[C@@]2(CCCN2C(=O)OC(C)(C)C)C1=O
InChIKey: ABAPCYNTEPGBNJ-FTGAXOIBSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13224
Assay: Positive allosteric modulation of human GluN2B receptor expressed in HEK293 cells by Whole-cell patch-clamp method
Measurement: EC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 327.38, ALogP -0.17, HBA 5, HBD 2, PSA 113.17, QED 0.7
Compound (SMILES): CCn1cc(S(=O)(=O)N2CCC3(CC2)C[C@@H](NC[C@H](O)COc2cccc(S(C)(=O)=O)c2)CO3)c(=O)c2ccccc21
InChIKey: PVXLIOIISUUKOQ-YADHBBJMSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: Homogeneous Time-Resolved Fluorescence Assay: Compounds were dissolved and serially diluted (5-fold) in DMSO to generate a 10-point dose response stock. The stock was then diluted 100-fold in assay buffer (PBS containing 1 mM IBMX) before a volume of 2.5 μL was added to the cells (the final, top concentration of compound in the dose-response is typically 10 or 100 μM). After a brief incubation, 2.5 μL of isoproterenol stock, prepared at a concentration 4 times its EC90 at the receptor of interest, was added to the wells. The EC90 for isoproterenol, a beta-adrenergic agonist, was determined in separate experiments using standard methods to measure agonist potencies.Following a 1-hour incubation at room temperature, 5 μL of cAMP-D2 Reagent diluted in Lysis Buffer was added to each well followed by 5 μL of Cryptate Reagent. Plates were further incubated at room temperature for 1 hour prior to reading. Time resolved fluorescence measurements were collected on a suitable, HTRF-capable plate reader.
Measurement: IC50 = 37650 nM (pChEMBL 4.420000076293945)
Descriptors: MW 619.76, ALogP 1.77, HBA 10, HBD 2, PSA 144.24, QED 0.35
Compound (SMILES): COc1ccc(Cc2sccc2O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
InChIKey: BUXGTLNOWLNUKF-SOVHRIKKSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Inhibition of SGLT1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 382.43, ALogP 0.53, HBA 8, HBD 4, PSA 108.61, QED 0.58
Compound (SMILES): C=C1[C@H](CO)[C@@H](O)C[C@@H]1n1cnc2c(=O)[nH]c(N)nc21.O
InChIKey: YXPVEXCTPGULBZ-WQYNNSOESA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of capsid in HBV infected in human HepAD38 cells assessed as reduction in tetracycline-induced cccDNA formation by measuring reduction in HBe antigen secretion after 14 days by ELISA
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 277.28, ALogP -0.83, HBA 7, HBD 4, PSA 130.05, QED 0.53
Compound (SMILES): Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1.O.O
InChIKey: FPKARFMSZDBYQF-ILKKLZGPSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Binding affinity towards human DRD1 in an in vitro assay with cellular components (NIBR assay) measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 279.19, ALogP -1.66, HBA 7, HBD 4, PSA 147.9, QED 0.45
Compound (SMILES): CC(=O)O.CC(=O)O.CC/N=C(\NCC)NCCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCCCN/C(=N/CC)NCC)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@@H](Cc1cccnc1)NC(=O)[C@@H](Cc1ccc(Cl)cc1)NC(=O)[C@@H](Cc1ccc2ccccc2c1)NC(C)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O
InChIKey: OVBICQMTCPFEBS-SATRDZAXSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Competitive antagonism of GnRH-induced response in the reporter gene assay
Measurement: Kd = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 1570.35
Compound (SMILES): CC[C@H]1[C@@H]2C[C@H]3[C@@H]4N(C)c5ccccc5[C@]45C[C@@H]([C@@H]2[C@H]5O)N3[C@@H]1O
InChIKey: CJDRUOGAGYHKKD-OVXZWHIBSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG K channel
Measurement: IC50 = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 326.44, ALogP 1.55, HBA 4, HBD 2, PSA 46.94, QED 0.82
Compound (SMILES): CC1(C)COc2ccc(F)cc2CN2c3nc4c(cnn4cc3OC[C@H]2C(F)F)C(=O)N1
InChIKey: ILAMRXVQSGVCJX-AWEZNQCLSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin)
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 447.42, ALogP 2.8, HBA 7, HBD 1, PSA 80.99, QED 0.62
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1Sc1ccnc(N)c1Cl
InChIKey: HISJAYUQVHMWTA-BLLLJJGKSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin)
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 451, ALogP 2.39, HBA 9, HBD 3, PSA 123.41, QED 0.64
Compound (SMILES): CNC(=O)c1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3)ccnc2cc1OC
InChIKey: JSPCKALGNNVYOO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: AXL Kinase Assay: Human Axl (residues H473-A894 with Q764R, 161 nM) was incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 250 μM KKSRGDYMTMQIG (SEO ID NO. 43) 10 mM magnesium acetate and 10 μM [γ-33P-ATP]. The reaction was initiated by the addition of the Mg/ATP mix. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of phosphoric acid to a concentration of 0.5%. A reaction aliquot of 10 μL was then spotted onto a P30 filtermat and washed four times for 4 minutes in 0.425% phosphoric acid and once in methanol prior to drying and scintillation counting. Incorporated 33P was measured using the Wallac Microbeta scintillation counter (Perkin Elmer).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 528.54, ALogP 4.89, HBA 6, HBD 3, PSA 118.65, QED 0.28
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4cc5c(n(-c6ccccc6)c4=O)CCCC5=O)nc3)c2cc1OC
InChIKey: WHMMKPWGWNYYFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MER (unknown origin) preincubated for 15 mins followed by substrate and ATP addition and measured after 3 hrs by ADP-Glo kinase assay
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 562.58, ALogP 5.36, HBA 9, HBD 1, PSA 121.64, QED 0.28
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(C6=CC[C@](COc7ncccc7C#N)(C(=O)O)CC6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: PQBROJOHKLMPKM-WJGXRGGQSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 4400 nM (pChEMBL 5.35699987411499)
Descriptors: MW 827.19, ALogP 8.78, HBA 8, HBD 2, PSA 132.62, QED 0.22
Compound (SMILES): O=C(c1nc2n(n1)[C@H](c1ccccc1)C[C@@H]2F)C1CC1
InChIKey: LMXPZWQVDDSYHH-RYUDHWBXSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Enzyme Assay: The ability of the receptor interacting protein kinase (RIPK1) to catalyze the hydrolysis of adenosine-5′-triphosphate (ATP) is monitored using the Transcreener ADP (adenosine-5′-diphosphate) assay (BellBrook Labs). Purified human RIP1 kinase domain (2-375) (50 nM) derived from a baculovirus-infected insect cell expression system is incubated with test compounds for 2 hours in 50 mM Hepes buffer (pH 7.5) containing 30 mM MgCl2, 1 mM dithiothreitol, 50 μM ATP, 0.002% Brij-35, and 0.5% dimethyl sulfoxide (DMSO). Reactions are quenched by the addition of 1× Bell Brooks Stop buffer B (20 mM Hepes (ph 7.5), 40 mM ethylenediaminetetraacetic acid and 0.02% Brij-35) containing an additional 12 mM EDTA and 55 ug/mL ADP2 antibody and 4 nM ADP-AlexaFluor® 633 tracer. The tracer bound to the antibody is displaced by the ADP generated during the RIP1K reaction, which causes a decrease in fluorescence polarization that is measured by laser excitation at 633 nm with a FP microplate reader M1000.
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 271.3, ALogP 2.87, HBA 4, HBD 0, PSA 47.78, QED 0.81
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cncc(-c3oncc3C)c2)n1
InChIKey: ADGOPPKEIZXKAZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42684
Assay: Kinase Assay: Kinase base buffer (50 mM HEPES, pH 7.5 0.0015% Brij-35; 10 mM MgCl2 2 mM DTT) and Stop buffer, (100 mM HEPES, pH 7.5 0.015% Brij-35; 0.2% Coating Reagent (50 mM EDTA) are prepared. Test compound is diluted in 100% DMSO to 50-times the desired final inhibitor concentration (the Stock Solution) and serially diluted in half-log increments resulting in final concentrations 250 μM to 75 μM, 25 μM, 7.5 μM, 2.5 μM, 0.75 μM, 0.25 μM, 75 nM, 25 nM, 7.5 nM in DMSO. 10 μl of each compound is placed in a 96-well plate as the intermediate plate. 90 μl of Kinase Buffer is added to to each well to prepare the intermediate plate.Figure US10906896-20210202-P00001Mix the compounds in intermediate plate for 10 min on shaker. For the assay of enzyme inhibitions, 5 μl of each well from the intermediate plate is transferred to a 384-well plate in duplicates, 10. Then 10 μl of 2.5× enzyme solution is added to each well of the 384-well assay plate and incubated for 10 min. Then enzyme substrate is added as 10 μl of 2.5×FAM-labeled peptide+ATP solution to each well of the 384-well assay plate. The reaction is allowed to proceed at 28° C. and quenched with the addition of 25 μl of stop buffer.
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 574.69, ALogP 5.55, HBA 9, HBD 2, PSA 112.31, QED 0.25
Compound (SMILES): CC(C)c1ccc(N(C)c2ccc3c(c2)OCC[C@H]3CNc2cnccc2C(=O)O)cc1
InChIKey: NDVITLLKZQXKGU-IBGZPJMESA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: JMJD3 Assay: The enzymatic assay of JMJD3 activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of JMJD3 was determined in 384-well plate format under the following reaction conditions: 5 nM JMJD3, 250 nM H3K27me3-biotin labeled peptide (Anaspec cat #64367), 0.4 to 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 27 (H3K27me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 750 nM H3K27me3-biotin labeled peptide and 1.2 to 6 μM alpha-ketoglutaric acid with 2 μL of 11-point serial diluted inhibitor in 3% DMSO were added to each well of plate, followed by the addition of 2 μl of 15 nM JMJD3 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μL of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K27me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio from the readout of 665/615 was calculated for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 431.54, ALogP 5.65, HBA 5, HBD 2, PSA 74.69, QED 0.5
Compound (SMILES): C=CC(=O)NC1CCN(c2ncc3ncnc(Nc4ccc(Oc5ccc6c(c5)ncn6C)c(C)c4)c3n2)CC1
InChIKey: YSGNGFPNTLERCR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 579 nM (pChEMBL 6.239999771118164)
Descriptors: MW 535.61, ALogP 4.42, HBA 10, HBD 2, PSA 122.98, QED 0.29
Compound (SMILES): C[C@H]1CN2CCNCc3ccc(C(=O)NCC(F)F)c1c32
InChIKey: KGOOOHQKLRUVSF-VIFPVBQESA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-DOI from 5-HT2C receptor (unknown origin) expressed in HEK293 cell membrane assessed as inhibition constant incubated for 1 hr by scintillation counter analysis
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 295.33, ALogP 1.71, HBA 3, HBD 2, PSA 44.37, QED 0.89
Compound (SMILES): C=CC(=O)N1CCN(c2c(C#N)c(=O)n(-c3c(C)ccnc3C(C)C)c3nc(-c4c(N)c(F)c(F)c(F)c4F)c(Cl)cc23)CC1
InChIKey: QRRJEUIQLZNPIO-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of His-tagged GDP-loaded KRAS G12C mutant (unknown origin) assessed as SOS1-mediated guanine nucleotide exchange preincubated with compound for 1 hrs followed by Flag-tagged SOS1 ExD and GTP addition and measured after 4 hrs by TR-FRET assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 640.04, ALogP 5.38, HBA 8, HBD 1, PSA 121.14, QED 0.1
Compound (SMILES): C[C@@H]1CN(c2cc(N3CCN(CC4=C(c5ccc(Cl)cc5)CC(C)(C)CC4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c2cc3cc[nH]c3nc2O1
InChIKey: CCDRQWAEZGRMTP-WJOKGBTCSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of Bcl-2 G101V mutant (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 923.54, ALogP 8.79, HBA 12, HBD 3, PSA 175.27, QED 0.08