lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1ncnn2c(CN3CCC(O)C3)cc(-c3cc(F)c(CO)c(F)c3)c12
InChIKey: BFUVVHGGORJPOX-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 375.38, ALogP 1.32, HBA 7, HBD 3, PSA 99.91, QED 0.64
Compound (SMILES): Nc1ncnn2c(CN3CCCC(O)C3)cc(-c3cc(F)c(CO)c(F)c3)c12
InChIKey: BJOJROYXDCYGRP-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 389.41, ALogP 1.71, HBA 7, HBD 3, PSA 99.91, QED 0.63
Compound (SMILES): CCc1cc(-c2cc([C@H]3CC[C@H](O)CC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: WYBNLHIHRKKQQO-CTYIDZIISA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 384.46, ALogP 3.19, HBA 6, HBD 3, PSA 96.67, QED 0.64
Compound (SMILES): COc1cc(-c2cc([C@H]3CC[C@H](O)CC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: RWORSPWJUTVGBW-AULYBMBSSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 386.43, ALogP 2.64, HBA 7, HBD 3, PSA 105.9, QED 0.64
Compound (SMILES): COc1cc(-c2cc(C3CCCNC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: DXSHKFJMROBTDG-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 371.42, ALogP 2.09, HBA 7, HBD 3, PSA 97.7, QED 0.65
Compound (SMILES): Cc1cc(-c2cc(C3CCCNC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: YXBKQVQHUYJBEU-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 355.42, ALogP 2.39, HBA 6, HBD 3, PSA 88.47, QED 0.67
Compound (SMILES): Cc1cc(-c2cc(C3CCNC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: MWTQNXALWBZYHH-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 341.39, ALogP 2, HBA 6, HBD 3, PSA 88.47, QED 0.68
Compound (SMILES): Nc1ncnn2c(C3(O)CCCCC3)cc(-c3cc(F)c(CO)c(F)c3)c12
InChIKey: QCUYUVQBHIYSJO-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 374.39, ALogP 2.9, HBA 6, HBD 3, PSA 96.67, QED 0.66
Compound (SMILES): NCc1nc(-c2cc(-c3cc(F)c(CO)c(F)c3)c3c(N)ncnn23)cs1
InChIKey: FWVKKGSYAGNETL-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 388.4, ALogP 2.33, HBA 8, HBD 3, PSA 115.35, QED 0.49
Compound (SMILES): CCc1cc(-c2cc(C3CCNC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: SRPGSKYQLDMWAK-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Radiometric Assay: ALKl (Invitrogen, Carlsbad, CA, USA) kinase activity was measured at ProQinase GmbH ( Freiburg. Germany) in a radiometric assay using gamma-33P-ATP and casein (Sigma, St. Louis, MO, USA) as substrate in 96-weli PerkinElmer FlashPlates (Boston, MA, USA). The compounds were tested at 10 concentrations in the range of 1 x 10"4 M to 3 x 10"9 M in a total volume of 50 ul with a finalDMSO concentration of 1 % each. The assay components were mixed in the order: 20 ul assay buffer (70 mM HEPES-NaOH, pi I 7.5. 3 mM MgCl2, 3 mM MnCl2, 2uM sodium orthovanadate, 1.2 mM DTT); - 5ul gamma-33P-ATP (1.0ug/50ug in water, approx. 6 x10E+5 cpm per well); 5 ul test compound solution (in 10% DMSO);10 ul substrate (200 ug/ml, 1.0ug/50ml final concentration) / enzyme (4 ug/ml, 20 ng/50ul = 5.5 nM final concentration) solution (1 : 1 mixture).
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 355.42, ALogP 2.25, HBA 6, HBD 3, PSA 88.47, QED 0.67
Compound (SMILES): CCc1cc(-c2cc(C3CCCNC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: PMFVTAQWEMKDLC-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Radiometric Assay: ALKl (Invitrogen, Carlsbad, CA, USA) kinase activity was measured at ProQinase GmbH ( Freiburg. Germany) in a radiometric assay using gamma-33P-ATP and casein (Sigma, St. Louis, MO, USA) as substrate in 96-weli PerkinElmer FlashPlates (Boston, MA, USA). The compounds were tested at 10 concentrations in the range of 1 x 10"4 M to 3 x 10"9 M in a total volume of 50 ul with a finalDMSO concentration of 1 % each. The assay components were mixed in the order: 20 ul assay buffer (70 mM HEPES-NaOH, pi I 7.5. 3 mM MgCl2, 3 mM MnCl2, 2uM sodium orthovanadate, 1.2 mM DTT); - 5ul gamma-33P-ATP (1.0ug/50ug in water, approx. 6 x10E+5 cpm per well); 5 ul test compound solution (in 10% DMSO);10 ul substrate (200 ug/ml, 1.0ug/50ml final concentration) / enzyme (4 ug/ml, 20 ng/50ul = 5.5 nM final concentration) solution (1 : 1 mixture).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 369.44, ALogP 2.64, HBA 6, HBD 3, PSA 88.47, QED 0.66
Compound (SMILES): CCc1cc(-c2cc(C(O)C3CC3)n3ncnc(N)c23)cc(F)c1CO
InChIKey: MDTULDMQZUPSIY-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Radiometric Assay: ALKl (Invitrogen, Carlsbad, CA, USA) kinase activity was measured at ProQinase GmbH ( Freiburg. Germany) in a radiometric assay using gamma-33P-ATP and casein (Sigma, St. Louis, MO, USA) as substrate in 96-weli PerkinElmer FlashPlates (Boston, MA, USA). The compounds were tested at 10 concentrations in the range of 1 x 10"4 M to 3 x 10"9 M in a total volume of 50 ul with a finalDMSO concentration of 1 % each. The assay components were mixed in the order: 20 ul assay buffer (70 mM HEPES-NaOH, pi I 7.5. 3 mM MgCl2, 3 mM MnCl2, 2uM sodium orthovanadate, 1.2 mM DTT); - 5ul gamma-33P-ATP (1.0ug/50ug in water, approx. 6 x10E+5 cpm per well); 5 ul test compound solution (in 10% DMSO);10 ul substrate (200 ug/ml, 1.0ug/50ml final concentration) / enzyme (4 ug/ml, 20 ng/50ul = 5.5 nM final concentration) solution (1 : 1 mixture).
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 356.4, ALogP 2.62, HBA 6, HBD 3, PSA 96.67, QED 0.65
Compound (SMILES): COc1cc(-c2cc(C(O)C3CC3)n3ncnc(N)c23)ccc1CO
InChIKey: CETAVAHOOHFRIY-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 340.38, ALogP 1.92, HBA 7, HBD 3, PSA 105.9, QED 0.66
Compound (SMILES): CC(C)c1cc(-c2cc(F)c(CO)c(F)c2)c2c(N)ncnn12
InChIKey: SOZVUFDUUVJPDR-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 318.33, ALogP 2.87, HBA 5, HBD 2, PSA 76.44, QED 0.78
Compound (SMILES): CC(O)c1cc(-c2cc(F)c(CO)c(F)c2)c2c(N)ncnn12
InChIKey: NNJNFOJAJSCTDY-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 320.3, ALogP 1.8, HBA 6, HBD 3, PSA 96.67, QED 0.68
Compound (SMILES): Nc1ncnn2c(N3CCOCC3)cc(-c3ccc(CO)c(F)c3)c12
InChIKey: RVNJRGXKAMFJDW-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Radiometric Assay: ALKl (Invitrogen, Carlsbad, CA, USA) kinase activity was measured at ProQinase GmbH ( Freiburg. Germany) in a radiometric assay using gamma-33P-ATP and casein (Sigma, St. Louis, MO, USA) as substrate in 96-weli PerkinElmer FlashPlates (Boston, MA, USA). The compounds were tested at 10 concentrations in the range of 1 x 10"4 M to 3 x 10"9 M in a total volume of 50 ul with a finalDMSO concentration of 1 % each. The assay components were mixed in the order: 20 ul assay buffer (70 mM HEPES-NaOH, pi I 7.5. 3 mM MgCl2, 3 mM MnCl2, 2uM sodium orthovanadate, 1.2 mM DTT); - 5ul gamma-33P-ATP (1.0ug/50ug in water, approx. 6 x10E+5 cpm per well); 5 ul test compound solution (in 10% DMSO);10 ul substrate (200 ug/ml, 1.0ug/50ml final concentration) / enzyme (4 ug/ml, 20 ng/50ul = 5.5 nM final concentration) solution (1 : 1 mixture).
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 343.36, ALogP 1.45, HBA 7, HBD 2, PSA 88.91, QED 0.75
Compound (SMILES): O=c1[nH]c2ccsc2c(=O)n1-c1cc(S(=O)(=O)N2CCCc3ccccc32)ccc1Cl
InChIKey: VWOZDBPRWRKKMI-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 473.96, ALogP 3.54, HBA 6, HBD 1, PSA 92.24, QED 0.49
Compound (SMILES): O=c1[nH]c2sccc2c(=O)n1-c1cc(S(=O)(=O)N2CCCc3ccccc32)ccc1Cl
InChIKey: OHSRIJBDPIVOLC-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 473.96, ALogP 3.54, HBA 6, HBD 1, PSA 92.24, QED 0.49
Compound (SMILES): Cc1cccc(N(C)S(=O)(=O)c2ccc(Cl)c(-n3c(=O)[nH]c4sccc4c3=O)c2)c1
InChIKey: KXKVDRUJUMGRSU-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 461.95, ALogP 3.53, HBA 6, HBD 1, PSA 92.24, QED 0.5
Compound (SMILES): O=C(O)c1scc2[nH]c(=O)n(-c3cc(S(=O)(=O)N4CCCc5ccccc54)ccc3Cl)c(=O)c12
InChIKey: OAPXLIYGMXPBRL-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 517.97, ALogP 3.23, HBA 7, HBD 2, PSA 129.54, QED 0.43
Compound (SMILES): Cc1ccccc1COc1ccc(Cl)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1
InChIKey: DJDXWWYJQLFGPO-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 442.88, ALogP 3.98, HBA 6, HBD 2, PSA 101.39, QED 0.49
Compound (SMILES): CNC(=O)c1scc2[nH]c(=O)n(-c3cc(S(=O)(=O)N4CCCc5ccccc54)ccc3Cl)c(=O)c12
InChIKey: HXDRHIVZXXJJCF-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 531.02, ALogP 2.9, HBA 7, HBD 2, PSA 121.34, QED 0.42
Compound (SMILES): COc1cccc(F)c1C(C)Oc1ccc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1
InChIKey: MHUIXNPUEJMNCS-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 474.44, ALogP 3.87, HBA 7, HBD 2, PSA 110.62, QED 0.44
Compound (SMILES): CN(C(=O)c1ccc(Cl)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1)c1ccccc1
InChIKey: YXEAJXIICFKZNU-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 455.88, ALogP 3.37, HBA 6, HBD 2, PSA 112.47, QED 0.49
Compound (SMILES): CC(C)(C(=O)c1ccc(Cl)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1)c1ccccc1
InChIKey: GESMLOLDXJKZBV-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 468.92, ALogP 4.25, HBA 6, HBD 2, PSA 109.23, QED 0.43
Compound (SMILES): COc1ccc(F)cc1C(C)(C)Sc1ccc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1
InChIKey: PUBRGANQNDOUMV-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 504.54, ALogP 4.75, HBA 7, HBD 2, PSA 101.39, QED 0.37
Compound (SMILES): CC(C)(c1ccccc1)S(=O)(=O)c1ccc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1
InChIKey: QXBWZICACGJAHJ-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 488.52, ALogP 3.29, HBA 7, HBD 2, PSA 126.3, QED 0.42
Compound (SMILES): COc1cc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)cc1OCc1c(OC)ccc(F)c1F
InChIKey: BMAAMIIYNNPHAB-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 508.43, ALogP 3.45, HBA 8, HBD 2, PSA 119.85, QED 0.39
Compound (SMILES): COCCOc1ccc(F)c(F)c1COc1ccc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)c1
InChIKey: VBCUMMKWZIJEND-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 522.46, ALogP 3.46, HBA 8, HBD 2, PSA 119.85, QED 0.32
Compound (SMILES): COc1cc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)cc1COc1c(OC)ccc(F)c1F
InChIKey: PMCRAVNJJCHBOB-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 508.43, ALogP 3.45, HBA 8, HBD 2, PSA 119.85, QED 0.39
Compound (SMILES): COc1cc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)cc1CN(C)c1c(F)cccc1F
InChIKey: MXOOXUTZJIIANK-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: FLIPR Calcium Assay: Antagonizing effect of compounds for human GnRHR1 was evaluated by change of calcium levels in GnRH-stimulated cells. After removing the culture medium of HEK293 cells transiently expressing human GnRHR1, cells were washed with 200 .mu.L piper well of the washing buffer (Hank's Balanced Salt Solutions, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 1.3 mM calcium chloride, 0.5 mM magnesium chloride, 0.4 mM magnesium sulfate). One hundred .mu.L of the Ca.sup.2+sensitive dye solution (FLIPR Calcium Assay Kit (Molecular Devices)) was added to the well, and the cells were incubated for 1 hour at 37.degree. C., 5% CO.sub.2. Then, intracellular calcium levels were determined under the following condition by using FLEX STATION (Molecular Devices). In the equipment, which was warmed to 37.degree. C., 50 .mu.L of test compound diluted with the measurement buffer (the washing buffer with 0.1% Albumin bovine serum) was added to the well.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 491.45, ALogP 3.5, HBA 7, HBD 2, PSA 104.63, QED 0.43
Compound (SMILES): c1ccc2c(-c3cnn4cc(-c5ccc(OCCN6CCOCC6)cc5)cnc34)ccnc2c1
InChIKey: DXLXRNZCYAYUED-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Kinase Assay: Kinase assays were performed using the assay kit by Reaction Biology Corp (Malvern, Pa.). The compounds were tested at 10 concentrations by 3-fold serial dilutions starting at 30 μM. Staurosporin was used as a control nonspecific kinase inhibitor. In vitro kinase reactions using purified kinases were carried out in the presence of 10 μM ATP and test compounds.
Measurement: IC50 = 42.77 nM (pChEMBL 7.369999885559082)
Descriptors: MW 451.53, ALogP 4.32, HBA 7, HBD 0, PSA 64.78, QED 0.38
Compound (SMILES): CN(C)CCCOc1ccc(-c2cnc3c(-c4ccnc5ccccc45)cnn3c2)cc1
InChIKey: MZIQJPGLZXVJCP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Kinase assays were performed using the assay kit by Reaction Biology Corp (Malvern, Pa.). The compounds were tested at 10 concentrations by 3-fold serial dilutions starting at 30 μM. Staurosporin was used as a control nonspecific kinase inhibitor. In vitro kinase reactions using purified kinases were carried out in the presence of 10 μM ATP and test compounds.
Measurement: IC50 = 2062 nM (pChEMBL 5.690000057220459)
Descriptors: MW 423.52, ALogP 4.94, HBA 6, HBD 0, PSA 55.55, QED 0.35
Compound (SMILES): Cc1c(-c2ccc(C(=O)N3CCN(C)CC3)cc2)c(=O)oc2c(C=O)c(O)ccc12
InChIKey: FEJCUYOATFXGBS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1alpha (GST-IRE-1alpha) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1alpha activity in vitro. Five ul of a reaction mixture comprising IX reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three ul of a 128 ng/ml IRE-1alpha preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound.After spinning the plates at 1200 rpm for 30 seconds, 3 ul of an IRE-1alpha human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 406.44, ALogP 2.67, HBA 6, HBD 1, PSA 91.06, QED 0.53
Compound (SMILES): CCN(CC)CCc1c(C)c2ccc(O)c(C=O)c2oc1=O
InChIKey: GPSHRPMCWFJHFE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1alpha (GST-IRE-1alpha) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1alpha activity in vitro. Five ul of a reaction mixture comprising IX reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three ul of a 128 ng/ml IRE-1alpha preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound.After spinning the plates at 1200 rpm for 30 seconds, 3 ul of an IRE-1alpha human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 303.36, ALogP 2.5, HBA 5, HBD 1, PSA 70.75, QED 0.66
Compound (SMILES): CC(C)c1cc(=O)oc2c(C=O)c(O)ccc12
InChIKey: DUNKAUOQDAHGTH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1alpha (GST-IRE-1alpha) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1alpha activity in vitro. Five ul of a reaction mixture comprising IX reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three ul of a 128 ng/ml IRE-1alpha preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound.After spinning the plates at 1200 rpm for 30 seconds, 3 ul of an IRE-1alpha human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 232.24, ALogP 2.43, HBA 4, HBD 1, PSA 67.51, QED 0.64
Compound (SMILES): COc1cc2c(C)c(Br)c(=O)oc2c(C=O)c1O
InChIKey: YPDZLYQNCHSQOJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1alpha (GST-IRE-1alpha) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1alpha activity in vitro. Five ul of a reaction mixture comprising IX reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three ul of a 128 ng/ml IRE-1alpha preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound.After spinning the plates at 1200 rpm for 30 seconds, 3 ul of an IRE-1alpha human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 313.1, ALogP 2.39, HBA 5, HBD 1, PSA 76.74, QED 0.68
Compound (SMILES): O=Cc1c(O)ccc2cc(-c3ccc(Br)cc3)c(=O)oc12
InChIKey: DJSPMRZGTUKARX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: IRE-1alpha Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1α (GST-IRE-1α) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1α activity in vitro. Five μl of a reaction mixture comprising 1× reaction buffer (5× reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three μl of a 128 ng/ml IRE-1α preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 μl of an IRE-1α human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2 (BH2) at the 3' end, are added to each well of a control plate. The plates are again spun at 1200 rpm for 30 seconds. Final concentrations for the assay are: 63 nM IRE-1α substrate, 5.82 ng IRE-1α protein, and 2.5 μM test compound. The plates are covered with lids and incubated for one hour at 30° C. The plates are then transferred to an ACQUEST™ microplate reader. Data is analyzed using data analysis software, and the percent activity of IRE-1α is calculated.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.15, ALogP 3.74, HBA 4, HBD 1, PSA 67.51, QED 0.57