lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC1CN(CC(=O)Nc2ccc(-n3ccccc3=O)cc2F)CC1NC(=O)c1ccc(Cl)s1
InChIKey: BOCLXHFYRGMFSC-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Protein construct 	Factor Xa purchased from R&D Systems- Source : Sf9 derived, Met1-Lys488, C-terminal 10-His tag 	Reconstituted purchased 25 ug to 100 ug/mL in 25 mM MES, 150 mM NaCl, 5 mM CalCl2, pH 6.0 	http://rndsystems.com/products/ACFP1063Compounds 	The 55 compounds were obtained from the K4DD collaboration partners:  	Sheraz Gul 	European Screening Port GmbHBuffers 	Coupling buffer :  	10 mM sodium acetate, pH 5.0 	Immobilisation : HBS- N, pH 7.5 	10 mM HEPES, 150 mM NaCl 	Assay running buffer : HBS-NP + 2 mM CaCl2 + 2% DMSO 	20 mM HEPES, 150 mM NaCl, 2 mM CaCl2, 0.05% Tween 20, 2% DMSO 	Sample buffer :  	Identical to assay running buffer 	Regeneration solution : 	 identical to assay running bufferKinetic titration experiments of 10 ug/ mL FXa immobilised onto a CM5 chip using standard amine coupling chemistry for use with SPR at 25C.Compounds assayed against the surface in a 1:3 dilution series in 2% DMSO
Measurement: Kd = 5.397 nM (pChEMBL 8.270000457763672)
Descriptors: MW 504.97, ALogP 2.76, HBA 7, HBD 2, PSA 92.67, QED 0.52
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ncccn3)ccc21
InChIKey: HSOCYPPAQYZHMJ-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 3 to 5 mins at -50 mV holding potential by patchXpress electrophysiology assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 552.53, ALogP 5.28, HBA 7, HBD 1, PSA 103.18, QED 0.31
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(C)c(NC(C)(C)C)nc34)[nH]c21
InChIKey: HLPARXMUJBJYFM-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding affinity to human PIM3 (16 to 317 residues) expressed in bacterial system by KINOMEScan assay
Measurement: Kd = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 365.44, ALogP 2.94, HBA 5, HBD 3, PSA 91.81, QED 0.65
Compound (SMILES): CCC(CC(C(=O)Nc1ccc(C(=O)O)cc1)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O)OC
InChIKey: NWTLKQWFPQKMLC-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 523.97, ALogP 4.74, HBA 7, HBD 2, PSA 130.65, QED 0.39
Compound (SMILES): Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)cn1
InChIKey: MJHOMTRKVMKCNE-NWDGAFQWSA-N
Target: Phosphorylase b kinase gamma catalytic chain, liver/testis isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P15735
Assay: Inhibition of human recombinant full length N-terminal GST-tagged PHKG2 expressed in baculovirus expression system by Z'-LYTE assay
Measurement: IC50 = 226 nM (pChEMBL 6.650000095367432)
Descriptors: MW 344.39, ALogP 1.55, HBA 6, HBD 3, PSA 97.86, QED 0.78
Compound (SMILES): O=C1NC(=O)[C@](CNC(=O)[C@@H](Cc2ccc(C(F)(F)F)cc2)C2CC2)(C2CC2)N1
InChIKey: JHOUEQAOHDTLPY-KXBFYZLASA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 50200 nM (pChEMBL 4.300000190734863)
Descriptors: MW 409.41, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ncccn3)ccc21
InChIKey: HSOCYPPAQYZHMJ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of slow inactivated human NaV1.7 expressed in HEK293 cells at -20 mV holding potential after 5 mins by IonWorks electrophysiology method
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 552.53, ALogP 5.28, HBA 7, HBD 1, PSA 103.18, QED 0.31
Compound (SMILES): CCC(CC(C(=O)Nc1ccc(C(=O)O)cc1)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O)OC
InChIKey: NWTLKQWFPQKMLC-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 523.97, ALogP 4.74, HBA 7, HBD 2, PSA 130.65, QED 0.39
Compound (SMILES): Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)cn1
InChIKey: MJHOMTRKVMKCNE-NWDGAFQWSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human recombinant GST-tagged RET cytoplasmic domain (658 to 1114 residues) expressed in baculovirus expression system by Z'-LYTE assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 344.39, ALogP 1.55, HBA 6, HBD 3, PSA 97.86, QED 0.78
Compound (SMILES): O=C1NC(=O)[C@](CNC(=O)[C@@H](Cc2ccc(C(F)(F)F)cc2)C2CC2)(C2CC2)N1
InChIKey: JHOUEQAOHDTLPY-KXBFYZLASA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs in the presence of 50% Lewis rat plasma by Alphascreen assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 409.41, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ncccn3)ccc21
InChIKey: HSOCYPPAQYZHMJ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human NaV1.7 expressed in HEK293 cells at -125 mV holding potential yielding 20 to 50% inactivation after 3 to 5 mins by PatchXpress automated electrophysiology method
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 552.53, ALogP 5.28, HBA 7, HBD 1, PSA 103.18, QED 0.31
Compound (SMILES): Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)cn1
InChIKey: MJHOMTRKVMKCNE-NWDGAFQWSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human recombinant N-terminal GST-tagged RET V804L mutant cytoplasmic domain (658 to 1114 residues) expressed in baculovirus expression system by Z'-LYTE assay
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 344.39, ALogP 1.55, HBA 6, HBD 3, PSA 97.86, QED 0.78
Compound (SMILES): O=C1NC(=O)[C@](CNC(=O)[C@@H](Cc2ccc(C(F)(F)F)cc2)C2CC2)(C2CC2)N1
InChIKey: JHOUEQAOHDTLPY-KXBFYZLASA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of human MMP3 using Mca-PQGL-(3-[2, 4-dinitrophenyl]-L-2, 3-diaminopropionyl)-AR-OH as substrate after 2 to 4 hrs by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 409.41, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)cn1
InChIKey: MJHOMTRKVMKCNE-NWDGAFQWSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human recombinant His-tagged VEGFR2 cytoplasmic domain (789 to1356 residues) expressed in baculovirus expression system by Z'-LYTE assay
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 344.39, ALogP 1.55, HBA 6, HBD 3, PSA 97.86, QED 0.78
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 = 8940 nM (pChEMBL 5.050000190734863)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition Assay: The inhibitions of activities of HDAC enzymes by the compounds N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluoro phenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 and N1'-[3-fluoro-4-[[7-[6-(hydroxyamino)-6-oxohexyloxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluo rophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 13 were measured by Reaction Biology Corporation (Reaction Biology Corp., One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA . http://www.reactionbiology.com/pages/hdac.htm). The HDAC enzymes tested include the following 11 HDAC isoforms: HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10 and HDAC11.Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 10 mM. The stock solution was diluted in 4-fold series starting from 10 mM to prepare 10 different dosages.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): CN(C)c1nc(NCc2ccc(NC(=O)C3CCN(Cc4ccccc4)CC3)cc2)c2ccccc2n1
InChIKey: DBCOLASKGYSTCT-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 1996 nM (pChEMBL 5.699999809265137)
Descriptors: MW 494.64, ALogP 5.16, HBA 6, HBD 2, PSA 73.39, QED 0.35
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3cccnc3)cc2)c2cc([N+](=O)[O-])ccc2n1
InChIKey: MRTPRLAHKIGQLP-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 > 23286 nM (pChEMBL 4.632999897003174)
Descriptors: MW 429.44, ALogP 3.84, HBA 8, HBD 3, PSA 134.97, QED 0.3
Compound (SMILES): CN(C)CC#Cc1ccc2nc(N(C)C)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: HXENEYFZJAQYSV-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 2007 nM (pChEMBL 5.699999809265137)
Descriptors: MW 496.59, ALogP 4.61, HBA 6, HBD 2, PSA 73.39, QED 0.36
Compound (SMILES): CCOCc1cc2cnc(NC3CCCCN3c3cccnc3)nc2n(C2CCCC2)c1=O
InChIKey: SHDOXKQVNTWZCX-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of Cdk2/Cyclin A (unknown origin) using retinoblastoma protein substrate and [gamma32P]ATP incubated for 15 mins by beta plate counter based assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 448.57, ALogP 4.27, HBA 8, HBD 1, PSA 85.17, QED 0.58
Compound (SMILES): CC(=O)Nc1nc2ccc(-c3nn(Cc4cc5cccc(C)c5c(=O)n4-c4ccccc4)c4ncnc(N)c34)cc2s1
InChIKey: VPJWIFAOPKDKPC-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 572.65, ALogP 5.3, HBA 10, HBD 2, PSA 133.61, QED 0.29
Compound (SMILES): O=C(O)C(F)(F)F.O=c1[nH]nc([C@]2(Cc3cccc(Nc4cc[nH]n4)n3)CC[C@@H](S(=O)(=O)c3cccc(Cl)c3Cl)CC2)o1
InChIKey: PUXFAKBQGPOLAW-IGVGDGLPSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human full-length N-terminal GST-tagged Aurora B/His-tagged INCENP (803 to 916 residues) using kemptide as substrate and [gamma33P]ATP after 45 mins by liquid scintillation counting method
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 549.44, ALogP 4.43, HBA 8, HBD 3, PSA 146.63, QED 0.31
Compound (SMILES): O=C(Nc1ccc(CNc2nc(N3CCN(c4ncccn4)CC3)nc3ccc(C(F)(F)F)cc23)cc1)C1CCN(Cc2ccc(F)cc2)CC1
InChIKey: WPFAWDSGQHLDJA-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 > 7145 nM (pChEMBL 5.145999908447266)
Descriptors: MW 699.76, ALogP 6.37, HBA 9, HBD 2, PSA 102.41, QED 0.17
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Br)cc4)ccc3o2)cc1)c1ccc(Br)cc1
InChIKey: FKHDTZDCOPGXLO-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES-ATPase activity expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by malachite green dye based fluorescence assay
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 663.37, ALogP 6.62, HBA 6, HBD 2, PSA 118.37, QED 0.2
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)Nc4ccc(Br)cc4)cc3)nc(N(C)C)nc2c1
InChIKey: MDSQKPYZQOGJBG-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 538 nM (pChEMBL 6.269999980926514)
Descriptors: MW 505.42, ALogP 6.02, HBA 5, HBD 3, PSA 82.18, QED 0.3
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)nc(N(C)Cc3ccccc3)nc2c1
InChIKey: MHBWTTBCDCFUFG-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 505.6, ALogP 6.58, HBA 5, HBD 2, PSA 70.15, QED 0.25
Compound (SMILES): Cc1ccn2nc([C@H](C)Nc3ncnc4[nH]cc(Cc5cccc(O)c5)c34)n(-c3ccccc3)c(=O)c12
InChIKey: FGCZLXKOGNAMNO-SFHVURJKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal His-tagged full length p110delta/recombinant human full length p85alpha using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 491.56, ALogP 4.53, HBA 8, HBD 3, PSA 113.13, QED 0.32
Compound (SMILES): Cc1cc(C)c2nc(N(C)C)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: PEMQPOZMRINTFV-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 1649 nM (pChEMBL 5.78000020980835)
Descriptors: MW 443.53, ALogP 5.32, HBA 5, HBD 2, PSA 70.15, QED 0.42
Compound (SMILES): N=C(N)NCCCCC(=O)Nc1ccc(C[C@H](NC(=O)[C@@H]2C=CCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: DKMKGQACSCOXGQ-VXKWHMMOSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 556.65, ALogP 1.02, HBA 6, HBD 6, PSA 194.78, QED 0.09
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc5nsnc5c4)ccc3o2)cc1)c1ccc2nsnc2c1
InChIKey: KNKNBKXGEGSPFV-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES-ATPase activity expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by malachite green dye based fluorescence assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 621.71, ALogP 5.11, HBA 12, HBD 2, PSA 169.93, QED 0.24
Compound (SMILES): O=C(Nc1ccc(CNc2nc(N3CCN(c4ncccn4)CC3)nc3ccc(C(F)(F)F)cc23)cc1)c1ccc(Cl)cc1
InChIKey: NJOUBZFFVPDTFJ-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 5190 nM (pChEMBL 5.289999961853027)
Descriptors: MW 619.05, ALogP 6.28, HBA 8, HBD 2, PSA 99.17, QED 0.22
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4ccc(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: MUDLWRHYTYCFBR-UZQPLGKSSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 520.94, ALogP 4.78, HBA 6, HBD 0, PSA 69.36, QED 0.5
Compound (SMILES): CC(C)(O)c1cn(-c2ccc(-c3cc(F)c(CO)c(S(C)(=O)=O)c3)cc2)c(Cc2c(Cl)cccc2Cl)n1
InChIKey: YIPWZEZDOVPNDU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13133
Assay: Displacement of [3H]-24,25-epoxycholesterol from human LXRalpha/RXRalpha expressed in baculovirus infected Sf9 cells by scintillation proximity analysis
Measurement: Ki = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 563.48, ALogP 5.7, HBA 6, HBD 2, PSA 92.42, QED 0.3
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cnn(CCO)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: PFRLTIZDNKOVEF-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 510.53, ALogP 3.06, HBA 10, HBD 2, PSA 129.67, QED 0.35
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)nc(N3CCN(C=O)CC3)nc2c1
InChIKey: DODQIWICPVDLJC-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 1858 nM (pChEMBL 5.730000019073486)
Descriptors: MW 498.56, ALogP 4.22, HBA 6, HBD 2, PSA 90.46, QED 0.37
Compound (SMILES): Cc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(NC(=O)CCCCNC(=N)N)cc2)C(=O)O)c2ccccc12
InChIKey: OSUIXCNIVHYKRR-UIOOFZCWSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 622.75, ALogP 2.71, HBA 6, HBD 6, PSA 194.78, QED 0.1
Compound (SMILES): CCC(Nc1ncnc2[nH]cnc12)c1cc2cccc(C)c2c(=O)n1-c1ccccc1C
InChIKey: SFUBQGSYRFAFQY-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 424.51, ALogP 4.84, HBA 6, HBD 2, PSA 88.49, QED 0.42
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3ccccc3F)cc2)c2cc(C)ccc2n1
InChIKey: BQKLYPNRJIXLKP-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 11965 nM (pChEMBL 4.920000076293945)
Descriptors: MW 415.47, ALogP 4.98, HBA 5, HBD 3, PSA 78.94, QED 0.41
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)c4ccc(Cl)nc4)cc3)nc(N(C)C)nc2c1
InChIKey: CTLKHRIZXUQDGT-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 318 nM (pChEMBL 6.5)
Descriptors: MW 446.94, ALogP 4.92, HBA 6, HBD 2, PSA 83.04, QED 0.41
Compound (SMILES): Cc1cccc2cc(Cn3nc(/C=C4/SC(=O)NC4=O)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: UPAUUDAUVQHKKA-VXLYETTFSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 527.54, ALogP 3.53, HBA 10, HBD 2, PSA 137.79, QED 0.34
Compound (SMILES): CCN1CCN(c2nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c3ccc(C)cc3n2)CC1
InChIKey: GALPVVQJEKJSTD-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf22C11 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 1146 nM (pChEMBL 5.940000057220459)
Descriptors: MW 498.61, ALogP 5.08, HBA 6, HBD 2, PSA 73.39, QED 0.37
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4ccc(O)c(F)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: OTTASAKAVHIAGP-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 510.5, ALogP 4.72, HBA 8, HBD 2, PSA 111.85, QED 0.36
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccc(O)c(F)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: MTIPJDDLMBTIGG-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 506.54, ALogP 4.89, HBA 8, HBD 2, PSA 111.85, QED 0.35
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Br)cc4)ccc3o2)cc1)c1ccc(Br)cc1
InChIKey: FKHDTZDCOPGXLO-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P10809
Assay: Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 663.37, ALogP 6.62, HBA 6, HBD 2, PSA 118.37, QED 0.2
Compound (SMILES): Cc1cccc2cc(Cn3nc(C#C[C@@H](C)O)c4c(N)ncnc43)n(-c3ccccc3O)c(=O)c12
InChIKey: NMDJSKSXBHJZIM-MRXNPFEDSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 466.5, ALogP 2.51, HBA 9, HBD 3, PSA 132.08, QED 0.35
Compound (SMILES): Cc1ccn2nc([C@H](C)Nc3ncnc4[nH]cc(Cc5cccc(O)c5)c34)n(-c3ccccc3)c(=O)c12
InChIKey: FGCZLXKOGNAMNO-SFHVURJKSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal His6-tagged full length p110alpha/recombinant human full length p85alpha using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 491.56, ALogP 4.53, HBA 8, HBD 3, PSA 113.13, QED 0.32
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc5nsnc5c4)ccc3o2)cc1)c1ccc2nsnc2c1
InChIKey: KNKNBKXGEGSPFV-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P10809
Assay: Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence based assay
Measurement: IC50 = 62000 nM (pChEMBL 4.210000038146973)
Descriptors: MW 621.71, ALogP 5.11, HBA 12, HBD 2, PSA 169.93, QED 0.24
Compound (SMILES): Cc1cccc2cc(Cn3nc(C4=CCOCC4)c4c(N)ncnc43)n(-c3ccccc3)c(=O)c12
InChIKey: KJDQWYKQMWVIEC-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.53, ALogP 3.87, HBA 8, HBD 1, PSA 100.85, QED 0.43
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4ccc(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: MUDLWRHYTYCFBR-UZQPLGKSSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma-secretase in CHO cells expressing human APP assessed as reduction in amyloid beta (1 to 42 residues) production after 24 hrs by ELISA
Measurement: EC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 520.94, ALogP 4.78, HBA 6, HBD 0, PSA 69.36, QED 0.5
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cnn(CCO)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: PFRLTIZDNKOVEF-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.53, ALogP 3.06, HBA 10, HBD 2, PSA 129.67, QED 0.35
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3cc(N)nc(N)n3)n(C3CC3)c(=O)c12
InChIKey: ISBNADRWBMFNJS-NSHDSACASA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 350.43, ALogP 2.77, HBA 7, HBD 3, PSA 111.85, QED 0.67
Compound (SMILES): CCC(Nc1ncnc2[nH]cnc12)c1cc2cccc(C)c2c(=O)n1-c1ccccc1C
InChIKey: SFUBQGSYRFAFQY-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 424.51, ALogP 4.84, HBA 6, HBD 2, PSA 88.49, QED 0.42
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3cnc4[nH]ccc4c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: GJIISJOBQSYKCH-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.58, ALogP 4.92, HBA 8, HBD 2, PSA 120.3, QED 0.35
Compound (SMILES): COc1ccccc1-n1c(Cn2nc(-c3cccc(O)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: AIJMYXQIMTYOJP-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 504.55, ALogP 4.45, HBA 9, HBD 2, PSA 121.08, QED 0.36
Compound (SMILES): C[C@H](Oc1cccc2cccnc12)C(=O)NC[C@@H](O)CN1Cc2ccccc2C1
InChIKey: MFLPZXZETDMETA-OXJNMPFZSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 > 101 nM (pChEMBL 6.995999813079834)
Descriptors: MW 391.47, ALogP 2.5, HBA 5, HBD 2, PSA 74.69, QED 0.65
Compound (SMILES): CC(=O)Nc1nc2ccc(-c3nn(Cc4cc5cccc(C)c5c(=O)n4-c4ccccc4)c4ncnc(N)c34)cc2s1
InChIKey: VPJWIFAOPKDKPC-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 572.65, ALogP 5.3, HBA 10, HBD 2, PSA 133.61, QED 0.29
Compound (SMILES): Cc1cccc2cc(Cn3nc(C#C[C@@H](C)O)c4c(N)ncnc43)n(-c3ccccc3O)c(=O)c12
InChIKey: NMDJSKSXBHJZIM-MRXNPFEDSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 466.5, ALogP 2.51, HBA 9, HBD 3, PSA 132.08, QED 0.35
Compound (SMILES): Cc1ccn2nc([C@H](C)Nc3ncnc4[nH]cc(Cc5cccc(O)c5)c34)n(-c3ccccc3)c(=O)c12
InChIKey: FGCZLXKOGNAMNO-SFHVURJKSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of recombinant human N-terminal His6-tagged full length p110beta/recombinant human full length p85alpha using PIP2 as substrate preincubated for 30 mins followed by substrate addition and HTRF assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 491.56, ALogP 4.53, HBA 8, HBD 3, PSA 113.13, QED 0.32
Compound (SMILES): Cc1cccc2cc(Cn3nc(C4=CCOCC4)c4c(N)ncnc43)n(-c3ccccc3)c(=O)c12
InChIKey: KJDQWYKQMWVIEC-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.53, ALogP 3.87, HBA 8, HBD 1, PSA 100.85, QED 0.43
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cnn(CCO)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: PFRLTIZDNKOVEF-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.53, ALogP 3.06, HBA 10, HBD 2, PSA 129.67, QED 0.35
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3cc(N)nc(N)n3)n(C3CC3)c(=O)c12
InChIKey: ISBNADRWBMFNJS-NSHDSACASA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 350.43, ALogP 2.77, HBA 7, HBD 3, PSA 111.85, QED 0.67
Compound (SMILES): CCC(Nc1ncnc2[nH]cnc12)c1cc2cccc(C)c2c(=O)n1-c1ccccc1C
InChIKey: SFUBQGSYRFAFQY-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 424.51, ALogP 4.84, HBA 6, HBD 2, PSA 88.49, QED 0.42
Compound (SMILES): COc1ccccc1-n1c(Cn2nc(-c3cccc(O)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: AIJMYXQIMTYOJP-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 504.55, ALogP 4.45, HBA 9, HBD 2, PSA 121.08, QED 0.36
Compound (SMILES): Cc1cccc2cc(Cn3nc(/C=C4/SC(=O)NC4=O)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: UPAUUDAUVQHKKA-VXLYETTFSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 527.54, ALogP 3.53, HBA 10, HBD 2, PSA 137.79, QED 0.34
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4ccc(O)c(F)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: OTTASAKAVHIAGP-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.5, ALogP 4.72, HBA 8, HBD 2, PSA 111.85, QED 0.36
Compound (SMILES): CCOP(=O)(OCC)c1ccc2cc1CN(C)C(=O)[C@H](Nc1ccc3c(N)nccc3c1)c1ccc(c(C)c1)[C@@H](C)COC(=O)N2
InChIKey: YIXUXJDCYJOAHT-WKRVVKTRSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of full-length human TF/recombinant human factor 7a assessed as decrease in conversion of factor 10 to factor 10a by measuring S2765 hydrolysis after 15 mins
Measurement: Ki = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 645.7, ALogP 6.49, HBA 9, HBD 3, PSA 145.11, QED 0.19