lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 4.24 nM (pChEMBL 8.369999885559082)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 82000 nM (pChEMBL 4.090000152587891)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 5345 nM (pChEMBL 5.269999980926514)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCC2)c1=O
InChIKey: YQRPDABJJCVAGZ-ZBYYUNFXSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Alpha-Opioid Receptor GTPgammaS Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/4 kappa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 uL/well) was transferred to 96-shallow well polypropylene plates containing 10 xL of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 uL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 C.
Measurement: EC50 = 1960 nM (pChEMBL 5.710000038146973)
Descriptors: MW 451.61, ALogP 5.55, HBA 5, HBD 1, PSA 75.43, QED 0.66
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(C(=O)O)nc4ccccc41)C3)C2
InChIKey: OWAGGONYNCKXDC-PCXLCNFCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Alpha-Opioid Receptor GTPgammaS Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/4 kappa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 uL/well) was transferred to 96-shallow well polypropylene plates containing 10 xL of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 uL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 C.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 449.6, ALogP 4.87, HBA 5, HBD 1, PSA 75.43, QED 0.72
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCCC2)c1=O
InChIKey: DNQQJKRDKSYDKP-JKHIJQBDSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: ORL-1 GTPgammaS Binding Assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4° C., and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at -80° C. Functional binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 ug/uL ORL-1 membrane protein, 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]G IPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.
Measurement: EC50 = 686 nM (pChEMBL 6.159999847412109)
Descriptors: MW 465.64, ALogP 5.94, HBA 5, HBD 1, PSA 75.43, QED 0.61
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of N-terminal GST-tagged BMX (1 to 675 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): CC(C)(C)OC(=O)c1ccc(-n2[nH]cc(-n3ccnn3)c2=O)nc1
InChIKey: HWQQDVNGHZIALS-UHFFFAOYSA-N
Target: Methylcytosine dioxygenase TET1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NFU7
Assay: Inhibition of tetracyclin/Dox-inducible N-terminal 3xFLAG/C-terminal GFP tagged human TET1 catalytic domain (1481 to 2136 residues) expressed in human U2OS cells assessed as reduction in 5-hydroxymethylcytosine level incubated for 24 hrs by immunofluorescence analysis
Measurement: EC50 = 79432.82 nM (pChEMBL 4.099999904632568)
Descriptors: MW 328.33, ALogP 1.1, HBA 8, HBD 1, PSA 107.69, QED 0.72
Compound (SMILES): O=c1c(-n2ccnn2)c[nH]n1-c1cc(N2CCOCC2)ncn1
InChIKey: IJMBOKOTALXLKS-UHFFFAOYSA-N
Target: Hypoxia-inducible factor 1-alpha inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWT6
Assay: Inhibition of FIH (unknown origin) by solid-phase extraction coupled to MS based assay
Measurement: IC50 = 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 314.31, ALogP -0.63, HBA 9, HBD 1, PSA 106.75, QED 0.69
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(-c3csc4c(-c5cnn(C[C@H](C)O)c5)cnc(N)c34)cc2)c1
InChIKey: VKBFHTIUXUCYRQ-KRWDZBQOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibtion Assay: Assays (200 μL final volume) were carried out in NUNC polypropylene deep well plates in 50 mM potassium phosphate buffer, pH 7.4, using a microtiter plate shaker in a 37° C. incubator. Pooled human liver microsomes (BD Gentest, 50 μg/mL) were incubated with 5 concentrations of test compound (from 0.1 μM to 10 μM), 1 mM NADPH (Sigma), and 2 μM midazolam (Sigma). A constant amount of dimethylsulfoxide (1%) was added to the incubations with the test compounds, and each analysis was performed in duplicate. For preincubation experiments (Pre), the microsomes, test compounds, and NADPH were mixed and incubated 30 minutes before addition of midazolam. For coincubation experiments (Co), the compounds, microsomes, and midazolam were mixed and the reaction initiated by addition of NADPH to the wells.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.61, ALogP 5.74, HBA 7, HBD 4, PSA 118.09, QED 0.24
Compound (SMILES): COc1ccc(NC(=O)Nc2ccc(-c3csc4c(-c5cnn(C[C@H](O)CO)c5)cnc(N)c34)cc2)cc1
InChIKey: BRTHUECZMVKNMQ-FQEVSTJZSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Enzyme Inhibtion Assay: To determine Aurora A and C activity of representative compounds of the invention, Active Aurora A or C enzyme was incubated in wells of a 384 well plate with biotinylated STK substrate-2 (Upstate), 1 mM ATP, and various concentrations of inhibitors in a Hepes buffer, pH 7.4 containing MgCl2, sodium othrovanadate, and Triton X-100. After 1 hour, the reaction was stopped with EDTA and anti-phospho-STK antibody Europium Cryptate (Upstate) and SA-XL665 (Upstate) were added to detect the phosphopeptide. The amount of phosphorylation was determined by the time-resolved fluorescence ratio of signals at 665 nm and 615 nm.
Measurement: IC50 = 570.14 nM (pChEMBL 6.239999771118164)
Descriptors: MW 530.61, ALogP 4.41, HBA 9, HBD 5, PSA 147.55, QED 0.2
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of N-terminal His6-tagged recombinant truncated human PHD2 (181 to 426 residues) extracted from Escherichia coli BL21 DE3 cells using HIF-1alpha CODD/2-OG as substrate by SPE-MS analysis
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 2 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3H407
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20ug membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 500uL binding buffer (5mM MgCl2, 5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 uM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: ORL-1 GTPgammaS Binding Assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4° C., and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at -80° C. Functional binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 ug/uL ORL-1 membrane protein, 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]G IPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.
Measurement: EC50 = 57.2 nM (pChEMBL 7.239999771118164)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCCC2)c1=O
InChIKey: DNQQJKRDKSYDKP-JKHIJQBDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Alpha-Opioid Receptor GTPgammaS Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/4 kappa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 uL/well) was transferred to 96-shallow well polypropylene plates containing 10 xL of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 uL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 C.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 465.64, ALogP 5.94, HBA 5, HBD 1, PSA 75.43, QED 0.61
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of N-terminal GST-tagged ITK (2 to 620 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): CC(C)(C)OC(=O)c1ccc(-n2[nH]cc(-n3ccnn3)c2=O)nc1
InChIKey: HWQQDVNGHZIALS-UHFFFAOYSA-N
Target: Methylcytosine dioxygenase TET1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NFU7
Assay: Inhibition of tetracyclin/Dox-inducible N-terminal 3xFLAG/C-terminal GFP tagged human TET1 catalytic domain (1481 to 2136 residues) expressed in human U2OS cells assessed as reduction in 5-hydroxymethylcytosine level incubated for 24 hrs by immunofluorescence analysis
Measurement: EC50 = 79000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 328.33, ALogP 1.1, HBA 8, HBD 1, PSA 107.69, QED 0.72
Compound (SMILES): O=c1c(-n2ccnn2)c[nH]n1-c1cc(N2CCOCC2)ncn1
InChIKey: IJMBOKOTALXLKS-UHFFFAOYSA-N
Target: Methylcytosine dioxygenase TET1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NFU7
Assay: Inhibition of tetracyclin/Dox-inducible N-terminal 3xFLAG/C-terminal GFP tagged human TET1 catalytic domain (1481 to 2136 residues) expressed in human U2OS cells assessed as reduction in 5-hydroxymethylcytosine level incubated for 24 hrs by immunofluorescence analysis
Measurement: EC50 ~ 100000 nM (pChEMBL 4)
Descriptors: MW 314.31, ALogP -0.63, HBA 9, HBD 1, PSA 106.75, QED 0.69
Compound (SMILES): COc1ccc(NC(=O)Nc2ccc(-c3csc4c(-c5cnn(C[C@H](O)CO)c5)cnc(N)c34)cc2)cc1
InChIKey: BRTHUECZMVKNMQ-FQEVSTJZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibtion Assay: Assays (200 μL final volume) were carried out in NUNC polypropylene deep well plates in 50 mM potassium phosphate buffer, pH 7.4, using a microtiter plate shaker in a 37° C. incubator. Pooled human liver microsomes (BD Gentest, 50 μg/mL) were incubated with 5 concentrations of test compound (from 0.1 μM to 10 μM), 1 mM NADPH (Sigma), and 2 μM midazolam (Sigma). A constant amount of dimethylsulfoxide (1%) was added to the incubations with the test compounds, and each analysis was performed in duplicate. For preincubation experiments (Pre), the microsomes, test compounds, and NADPH were mixed and incubated 30 minutes before addition of midazolam. For coincubation experiments (Co), the compounds, microsomes, and midazolam were mixed and the reaction initiated by addition of NADPH to the wells.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 530.61, ALogP 4.41, HBA 9, HBD 5, PSA 147.55, QED 0.2
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Aspartyl/asparaginyl beta-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q12797
Assay: Inhibition of AspH (unknown origin)
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 4.08 nM (pChEMBL 8.390000343322754)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) measured by ADP-Glo assay
Measurement: IC50 = 31.7 nM (pChEMBL 7.5)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Substance-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21452
Assay: Displacement of [125I]NKA from recombinant human NK2 measured after 60 mins by scintillation counting method
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: ORL-1 GTPgammaS Binding Assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4° C., and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as a standard. Aliquots of the ORL-1 receptor membranes were stored at -80° C. Functional binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 ug/uL ORL-1 membrane protein, 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]G IPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.
Measurement: EC50 = 4.03 nM (pChEMBL 8.390000343322754)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Mu-Opioid GTPgammaS Binding Assay: [35S]GTP gamma S functional assays were conducted using freshly thawed mu-receptor membranes. Assay reactions were prepared by sequentially adding the following reagents to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice (final concentrations indicated): membrane protein (0.026 mg/mL), saponin (10 mg/mL), GDP (3 mM) and [35S]GTP gamma S (0.20 nM; NEN). The prepared membrane solution (1904/well) was transferred to 96-shallow well polypropylene plates containing 10 uL of 20x concentrated stock solutions of the agonist DAMGO ([D-Ala2, N-methyl-Phe4 Gly-ol5]-enkephalin) prepared in DMSO. Plates were incubated for 30 min at about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard, Meriden, Conn.) using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by three filtration washes with 200 mL of ice-cold wash buffer.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 expressed in baculovirus expression system incubated for 1 hr by Z'lyte assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 14.3 nM (pChEMBL 7.840000152587891)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Bifunctional peptidase and arginyl-hydroxylase JMJD5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N371
Assay: Inhibition of JMJD5 (unknown origin)
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 7.18 nM (pChEMBL 8.140000343322754)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology method
Measurement: IC50 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Mu-Opioid GTPgammaS Binding Assay: [35S]GTP gamma S functional assays were conducted using freshly thawed mu-receptor membranes. Assay reactions were prepared by sequentially adding the following reagents to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice (final concentrations indicated): membrane protein (0.026 mg/mL), saponin (10 mg/mL), GDP (3 mM) and [35S]GTP gamma S (0.20 nM; NEN). The prepared membrane solution (1904/well) was transferred to 96-shallow well polypropylene plates containing 10 uL of 20x concentrated stock solutions of the agonist DAMGO ([D-Ala2, N-methyl-Phe4 Gly-ol5]-enkephalin) prepared in DMSO. Plates were incubated for 30 min at about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard, Meriden, Conn.) using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by three filtration washes with 200 mL of ice-cold wash buffer.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Alpha-Opioid Receptor GTPgammaS Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/4 kappa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 uL/well) was transferred to 96-shallow well polypropylene plates containing 10 xL of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 uL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 C.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of recombinant human N-terminal GST-tagged ERBB4 catalytic domain expressed in baculovirus expression system incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase Fgr (SINGLE PROTEIN), Homo sapiens
UniProt: P09769
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of HIF-PHD2 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 13700 nM (pChEMBL 4.860000133514404)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 2 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3H407
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: COTYYZPYDJKKIS-KQMWNOITSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Alpha-Opioid Receptor GTPgammaS Functional Assay: Functional [35S]GTPgammaS binding assays were conducted as follows. Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 ug/4 kappa membrane protein (in-house), 10 ug/mL saponin, 3 uM GDP and 0.20 nM [35S]GTPgammaS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 uL/well) was transferred to 96-shallow well polypropylene plates containing 10 xL of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 uL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 C.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 435.57, ALogP 4.62, HBA 5, HBD 1, PSA 75.43, QED 0.76
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 3825 nM (pChEMBL 5.420000076293945)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of recombinant human His-tagged LCK expressed in baculovirus expression system incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Enzyme Assay: The EGLN-1 (or EGLN-3) enzyme activity is determined using mass spectrometry (matrix-assisted laser desorption ionization, time-of-flight MS, MALDI-TOF MS—for assay details, see reference (Greis et al., 2006).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 2.38 nM (pChEMBL 8.619999885559082)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-5/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P28472
Assay: Displacement of [3H]-flumazenil from human GABAA alpha5beta3gamma2 expressed in HEK293 cell membranes measured after 2 hrs by liquid scintillation counting method
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 202.8 nM (pChEMBL 6.690000057220459)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of recombinant human GST-tagged full length ITK expressed in baculovirus expression system incubated for 1 hr by Z'lyte assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase HCK (SINGLE PROTEIN), Homo sapiens
UniProt: P08631
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 cells per well in DMEM (10% FBS, 1% NEAA, 0.1% glutamine). Following overnight incubation, the cells are washed with 100 uL of Opti-MEM (Gibco, Carlsbad, Calif.) to remove serum. Compound in DMSO is serially diluted (beginning with 100 μM) in Opti-MEM and added to the cells. The conditioned media is analyzed for VEGF with a Quantikine human VEGF immunoassay kit (R&D Systems, Minneapolis, Minn.).
Measurement: EC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CC3CCCC(C3)C2)c1=O
InChIKey: WKPMMJFYKKQWLO-WZMLIQCHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 6143 nM (pChEMBL 5.210000038146973)
Descriptors: MW 421.54, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of recombinant human His-tagged full length BLK expressed in baculovirus expression system incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Binding affinity to full length PHD2 (181 to 426 residues) (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 256.9 nM (pChEMBL 6.590000152587891)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR (668 to 1210 residues) expressed in baculovirus expression system incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47