lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C1=N[C@@H]2[C@@H](OCc3ccccc3)[C@H](COCc3ccccc3)[C@@H](C(O)C3SCCCS3)O[C@@H]2S1
InChIKey: IYBLYBDKLNYSLR-RAANROPKSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions are carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction is 0.7 nM. Test compound of varying concentrations is added to the enzyme prior to initiation of the reaction. The reaction is performed at room temperature in a 96-well plate and is initiated with the addition of substrate. The production of fluorescent product is measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production is determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 560.81, ALogP 4.72, HBA 9, HBD 1, PSA 63.52, QED 0.47
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCCC[C@H](N1CCC(c3cccc(Cl)c3)OC1=O)c1nc-2c[nH]1
InChIKey: OASTUTJTQAOEFC-NQCNTLBGSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 3396 nM (pChEMBL 5.46999979019165)
Descriptors: MW 538, ALogP 6.05, HBA 6, HBD 3, PSA 125.65, QED 0.37
Compound (SMILES): COC(=O)Nc1ccc2c(c1)N[C@@H](C(=O)OC)CCCC[C@H](N1CCC(c3cccc(Cl)c3)OC1=O)c1nc-2c[nH]1
InChIKey: SJQOENUGWSOLMZ-DJJHXFJNSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 12.24 nM (pChEMBL 7.909999847412109)
Descriptors: MW 582.06, ALogP 6.06, HBA 8, HBD 3, PSA 134.88, QED 0.25
Compound (SMILES): COC(=O)Nc1ccc2c(c1)N[C@@H](C(=O)OC)CCCC[C@H](N1CCC(c3cc(Cl)ccc3OC(F)F)OC1=O)c1nc-2c(C#N)[nH]1
InChIKey: RGSXXHYYBMCKMJ-HHDGPCQCSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 41.77 nM (pChEMBL 7.380000114440918)
Descriptors: MW 673.07, ALogP 6.53, HBA 10, HBD 3, PSA 167.9, QED 0.19
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CCC(c3cccc(Cl)c3)CC1=O)c1nc-2c[nH]1
InChIKey: YMEHWISYYMKMFO-BTQSIKNTSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 548.04, ALogP 6.03, HBA 5, HBD 3, PSA 116.42, QED 0.35
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)C(C)CCC[C@H](N1CC[C@H](c3c(F)ccc(Cl)c3F)OC1=O)c1cc-2cnn1
InChIKey: BOAJBXZDKGNIQB-XDOMWJSLSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 600.02, ALogP 6.64, HBA 7, HBD 2, PSA 122.75, QED 0.32
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCC(c3c(Cl)ccc(Cl)c3F)NC1=O)c1nc-2c[nH]1
InChIKey: FGJUHWGLUJLNMV-SROYVJGESA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 6.83 nM (pChEMBL 8.170000076293945)
Descriptors: MW 603.48, ALogP 6.66, HBA 5, HBD 4, PSA 128.45, QED 0.25
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCN(c3cccc(Cl)c3F)CC1=O)c1cc-2ccn1
InChIKey: JEHFAGDYMDSZFD-CJAUYULYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 7.46 nM (pChEMBL 8.130000114440918)
Descriptors: MW 580.06, ALogP 5.87, HBA 6, HBD 2, PSA 103.87, QED 0.4
Compound (SMILES): C[C@@H]1CCC[C@H](N2CC[C@H](c3c(F)ccc(Cl)c3F)OC2=O)c2cc(ccn2)-c2cc(C(=O)O)ccc2NC1=O
InChIKey: PAWKAWDJVQSALO-ZNZBMKLDSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 569.99, ALogP 6.76, HBA 5, HBD 2, PSA 108.83, QED 0.34
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CCC(C)(c3c(F)ccc(Cl)c3F)OC1=O)c1nc-2c(Cl)[nH]1
InChIKey: RYHYEVJNCKWHNX-LBJSYYEUSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 2461 nM (pChEMBL 5.610000133514404)
Descriptors: MW 634.47, ALogP 7.32, HBA 6, HBD 3, PSA 125.65, QED 0.2
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCCC(N1CC(=O)N(c3c(C(F)(F)F)ccc(Cl)c3F)CC1=O)c1cc-2ccn1
InChIKey: PJKTZRSONLMQJO-YAOANENCSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 662.04, ALogP 6.41, HBA 6, HBD 2, PSA 120.94, QED 0.31
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CCC(c3cc(Cl)ccn3)NC1=O)c1nc-2c[nH]1
InChIKey: CMXWSPLYQAIUKA-KKJWHPGESA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 24.42 nM (pChEMBL 7.610000133514404)
Descriptors: MW 550.02, ALogP 5.18, HBA 6, HBD 4, PSA 141.34, QED 0.33
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CC[C@H](c3c(F)ccc(Cl)c3F)NC1=O)c1nc-2c[nH]1
InChIKey: VVYCRGXPQOKNCU-MNCQGGSDSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 585.01, ALogP 6.06, HBA 5, HBD 4, PSA 128.45, QED 0.22
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCC(c3nccc(Cl)c3F)NC1=O)c1nc-2c[nH]1
InChIKey: IUGQXUQEKTZPLY-OWRKKYCOSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 570.03, ALogP 5.4, HBA 6, HBD 4, PSA 141.34, QED 0.33
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CC[C@@H](c3c(F)ccc(Cl)c3F)NC1=O)c1nc-2c[nH]1
InChIKey: QXYWBBTYOMYKHI-LNHNDHHWSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 587.03, ALogP 6.14, HBA 5, HBD 4, PSA 128.45, QED 0.27
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CC[C@@H](c3nccc(Cl)c3F)N(C)C1=O)c1nc-2c[nH]1
InChIKey: XXZGTDCBOMGCAM-YDFBLROQSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 329.8 nM (pChEMBL 6.480000019073486)
Descriptors: MW 584.05, ALogP 5.74, HBA 6, HBD 3, PSA 132.55, QED 0.36
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CC[C@H](c3nccc(Cl)c3F)N(C)C1=O)c1nc-2c[nH]1
InChIKey: XXZGTDCBOMGCAM-RTOPAQNCSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 28.79 nM (pChEMBL 7.539999961853027)
Descriptors: MW 584.05, ALogP 5.74, HBA 6, HBD 3, PSA 132.55, QED 0.36
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CC[C@H](c3cc(Cl)ccc3OC(F)F)OC1=O)c1nc-2c[nH]1
InChIKey: FRJQYBHNFZRSQW-FRKXHHAISA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 7.46 nM (pChEMBL 8.130000114440918)
Descriptors: MW 616.02, ALogP 6.81, HBA 7, HBD 3, PSA 134.88, QED 0.27
Compound (SMILES): COC(=O)Nc1ccc2c(c1)N[C@@H](C(=O)OC)CCCC[C@H](N1CCC(c3cccc(Cl)c3)OC1=O)c1nc-2c(C#N)[nH]1
InChIKey: UVNQNQVOCFGZCT-DJJHXFJNSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 13.35 nM (pChEMBL 7.880000114440918)
Descriptors: MW 607.07, ALogP 5.93, HBA 9, HBD 3, PSA 158.67, QED 0.24
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CC[C@@H](c3c(F)ccc(Cl)c3F)OC1=O)c1cc-2ccn1
InChIKey: HWWPEQUIKVTKQH-MNCIPDHPSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 599.03, ALogP 7.24, HBA 6, HBD 2, PSA 109.86, QED 0.31
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@@H](C)CCC[C@H](N1CC[C@@H](c3c(F)ccc(Cl)c3F)OC1=O)c1ccnc-2c1
InChIKey: RRFKLVWKCVSQSZ-BBBIZMJLSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 599.03, ALogP 7.24, HBA 6, HBD 2, PSA 109.86, QED 0.31
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCC(c3c(C(F)(F)F)ccc(Cl)c3F)OC1=O)c1cc-2ccn1
InChIKey: SWSGHGVAWHIRMT-JBDIKNGWSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 69.32 nM (pChEMBL 7.159999847412109)
Descriptors: MW 649.04, ALogP 8.12, HBA 6, HBD 2, PSA 109.86, QED 0.28
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CCCC[C@H](N1CCC(c3cccc(Cl)c3)CC1=O)c1nc-2c[nH]1
InChIKey: ZGVMWYBKAWCLGZ-LUTIACGYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 9.48 nM (pChEMBL 8.020000457763672)
Descriptors: MW 536.03, ALogP 5.87, HBA 5, HBD 3, PSA 116.42, QED 0.39
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCC(c3cccc(Cl)c3)CC1=O)c1cc-2ccn1
InChIKey: CUYPUVJQAGSMBN-GFNMQIPBSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 561.08, ALogP 6.79, HBA 5, HBD 2, PSA 100.63, QED 0.37
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CCN(c3cccc(Cl)c3)C(C)C1=O)c1nc-2c[nH]1
InChIKey: KRCJNFHXZICOIG-CHJXXOIQSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as inhibitors of the coagulation Factors XIa, VIIa, IXa, Xa, XIIa, plasma kallikrein or thrombin, can be determined using a relevant purified serine protease, respectively, and an appropriate synthetic substrate. The rate of hydrolysis of the chromogenic or fluorogenic substrate by the relevant serine protease was measured both in the absence and presence of compounds of the present invention. Assays were conducted at room temperature or at 37Â° C. Hydrolysis of the substrate resulted in the release of pNA (para nitroaniline), which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nm, or the release of AMC (amino methylcoumarin), which was monitored spectrofluorometrically by measuring the increase in emission at 460 nm with excitation at 380 nm. A decrease in the rate of absorbance or fluorescence change in the presence of inhibitor is indicative of enzyme inhibition.
Measurement: Ki = 983.8 nM (pChEMBL 6.010000228881836)
Descriptors: MW 563.06, ALogP 5.37, HBA 6, HBD 3, PSA 119.66, QED 0.37
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-YKATVRGKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@@H]1CCCN1
InChIKey: BXYUWIKGVQXGEA-ZUURVNMSSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Cell Proliferation Inhibition Assay: The following in vitro assay is to determine the activity of the tested compounds for inhibiting the proliferation of cancer cells, which has high expression of EGFR. The activity is represented by the IC50 value. The general procedures of the assay are given as follows: The cancer cells A431 that highly expressing EGFR (Institute of biochemistry and cell biology) were chosen and seeded to 96-well cell culture plate at a suitable concentration (e.g., 5000 cells/mL medium). The cells then were incubated in carbon dioxide (CO2) incubator until they reached 85% confluency. Then, the cell culture medium was replaced by fresh one with tested compounds added in it at serial concentrations (general 6 to 7 concentrations). Then the cells were put back to the incubator and cultured continuously. 72 hours later, the activity of the tested compounds for inhibiting the cell proliferation was determined by using Sulforhodamine B (SRB) method.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 569.06, ALogP 6.12, HBA 8, HBD 3, PSA 121.19, QED 0.2
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@@H]1C[C@@H](O)CN1C
InChIKey: MGJMZWXLGRKRAN-XLGCXCGNSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 599.09, ALogP 5.44, HBA 9, HBD 3, PSA 132.63, QED 0.2
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Cell Proliferation Inhibition Assay: The following in vitro assay is to determine the activity of the tested compounds for inhibiting the proliferation of cancer cells, which has high expression of EGFR. The activity is represented by the IC50 value. The general procedures of the assay are given as follows: The cancer cells A431 that highly expressing EGFR (Institute of biochemistry and cell biology) were chosen and seeded to 96-well cell culture plate at a suitable concentration (e.g., 5000 cells/mL medium). The cells then were incubated in carbon dioxide (CO2) incubator until they reached 85% confluency. Then, the cell culture medium was replaced by fresh one with tested compounds added in it at serial concentrations (general 6 to 7 concentrations). Then the cells were put back to the incubator and cultured continuously. 72 hours later, the activity of the tested compounds for inhibiting the cell proliferation was determined by using Sulforhodamine B (SRB) method.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/[C@@H]1CCCN1C
InChIKey: JZQOPZNZLUYLTR-DYLHUKMJSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 469.95, ALogP 5.15, HBA 6, HBD 2, PSA 79.38, QED 0.47
Compound (SMILES): COCCOc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: JLZPLOMYCANQFI-DBWMJRBXSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 499.97, ALogP 4.78, HBA 7, HBD 2, PSA 88.61, QED 0.32
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: JZQOPZNZLUYLTR-MNDMWVCDSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Time-Resolved Fluorescence Assay: The following assay may be used to determine the activity of the compounds of the invention for inhibiting EGFR kinase activity. The half maximal inhibitory concentration IC50 (the concentration of the tested compound showing 50% inhibition of the enzyme activity) of each compound was determined by incubating several different concentrations of the tested compounds with a specific enzyme and substrate. EGFR kinase used in this assay is a human-derived recombinant protein (Cell signaling technology, #7908), which was reacted with peptide substrate and different concentrations of tested compounds in a buffer solution containing 60 mM HEPES (pH7.5), 5 mM MgCl2, 5 mM MnCl2, 3 μM Na3VO4, 1.25 M DTT (1000×) and 20 μM ATP at 25° C., for 45 minutes.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 469.95, ALogP 5.15, HBA 6, HBD 2, PSA 79.38, QED 0.47
Compound (SMILES): CCOC(=O)CNC(=O)NCc1ccc(N)cc1
InChIKey: UCMPTJMHPJQEED-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase G (SINGLE PROTEIN), Homo sapiens
UniProt: Q13427
Assay: Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry. 1991 Jun. 25; 30(25):6127-34). The assay buffer (25 mM Hepes, 100 mM NaCl, pH 7.8) and CypA, B or D (1900 nM stock solution) were pre-cooled to 4 C., to which then was added 5 uL of 50 mg/ml chymotrypsin in 1 mM HCl. The reaction was initiated by adding 20 uL of 3.2 mM peptide substrate (Suc-Ala-Ala-cis-Pro-Phe-pNA) in LiCl/TFE solution with rapid inversion. After a delay from the onset of mixing, the absorbance of p-nitroaniline was followed at 390 nM until the reaction was complete (1 min). The final concentration of LiCl in the assay was 20 mM; TFE was present at a concentration of 4% (v/v). Absorbance readings were collected every 1 s by spectrophotometer.
Measurement: IC50 = 16800 nM (pChEMBL 4.78000020980835)
Descriptors: MW 251.29, ALogP 0.63, HBA 4, HBD 3, PSA 93.45, QED 0.53
Compound (SMILES): CCOC(=O)C1CCCN(C(=O)CNC(=O)NCc2ccc(N)cc2)C1
InChIKey: AOYNGKLTOSMOQF-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase B (SINGLE PROTEIN), Homo sapiens
UniProt: P23284
Assay: Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry. 1991 Jun. 25; 30(25):6127-34). The assay buffer (25 mM Hepes, 100 mM NaCl, pH 7.8) and CypA, B or D (1900 nM stock solution) were pre-cooled to 4 C., to which then was added 5 uL of 50 mg/ml chymotrypsin in 1 mM HCl. The reaction was initiated by adding 20 uL of 3.2 mM peptide substrate (Suc-Ala-Ala-cis-Pro-Phe-pNA) in LiCl/TFE solution with rapid inversion. After a delay from the onset of mixing, the absorbance of p-nitroaniline was followed at 390 nM until the reaction was complete (1 min). The final concentration of LiCl in the assay was 20 mM; TFE was present at a concentration of 4% (v/v). Absorbance readings were collected every 1 s by spectrophotometer.
Measurement: IC50 = 75100 nM (pChEMBL 4.119999885559082)
Descriptors: MW 362.43, ALogP 0.87, HBA 5, HBD 3, PSA 113.76, QED 0.51
Compound (SMILES): Nc1ccc(CNC(=O)NCC(=O)N2CCOC(CN3C(=O)c4ccccc4C3=O)C2)cc1
InChIKey: LQMKNSYNNIHCSU-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase B (SINGLE PROTEIN), Homo sapiens
UniProt: P23284
Assay: Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry. 1991 Jun. 25; 30(25):6127-34). The assay buffer (25 mM Hepes, 100 mM NaCl, pH 7.8) and CypA, B or D (1900 nM stock solution) were pre-cooled to 4 C., to which then was added 5 uL of 50 mg/ml chymotrypsin in 1 mM HCl. The reaction was initiated by adding 20 uL of 3.2 mM peptide substrate (Suc-Ala-Ala-cis-Pro-Phe-pNA) in LiCl/TFE solution with rapid inversion. After a delay from the onset of mixing, the absorbance of p-nitroaniline was followed at 390 nM until the reaction was complete (1 min). The final concentration of LiCl in the assay was 20 mM; TFE was present at a concentration of 4% (v/v). Absorbance readings were collected every 1 s by spectrophotometer.
Measurement: IC50 = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 451.48, ALogP 0.59, HBA 6, HBD 3, PSA 134.07, QED 0.43
Compound (SMILES): COc1ccc(N(C)C(=O)CNC(=O)NCc2ccc(N)cc2)cc1
InChIKey: RWIUYNXOFPIAEB-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase B (SINGLE PROTEIN), Homo sapiens
UniProt: P23284
Assay: Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry. 1991 Jun. 25; 30(25):6127-34). The assay buffer (25 mM Hepes, 100 mM NaCl, pH 7.8) and CypA, B or D (1900 nM stock solution) were pre-cooled to 4 C., to which then was added 5 uL of 50 mg/ml chymotrypsin in 1 mM HCl. The reaction was initiated by adding 20 uL of 3.2 mM peptide substrate (Suc-Ala-Ala-cis-Pro-Phe-pNA) in LiCl/TFE solution with rapid inversion. After a delay from the onset of mixing, the absorbance of p-nitroaniline was followed at 390 nM until the reaction was complete (1 min). The final concentration of LiCl in the assay was 20 mM; TFE was present at a concentration of 4% (v/v). Absorbance readings were collected every 1 s by spectrophotometer.
Measurement: IC50 = 27800 nM (pChEMBL 4.559999942779541)
Descriptors: MW 342.4, ALogP 1.74, HBA 4, HBD 3, PSA 96.69, QED 0.7
Compound (SMILES): CN(C(=O)CNC(=O)NCc1ccc(N)cc1)c1ccccc1
InChIKey: KLGPLJDVBFPMKH-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase B (SINGLE PROTEIN), Homo sapiens
UniProt: P23284
Assay: Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry. 1991 Jun. 25; 30(25):6127-34). The assay buffer (25 mM Hepes, 100 mM NaCl, pH 7.8) and CypA, B or D (1900 nM stock solution) were pre-cooled to 4 C., to which then was added 5 uL of 50 mg/ml chymotrypsin in 1 mM HCl. The reaction was initiated by adding 20 uL of 3.2 mM peptide substrate (Suc-Ala-Ala-cis-Pro-Phe-pNA) in LiCl/TFE solution with rapid inversion. After a delay from the onset of mixing, the absorbance of p-nitroaniline was followed at 390 nM until the reaction was complete (1 min). The final concentration of LiCl in the assay was 20 mM; TFE was present at a concentration of 4% (v/v). Absorbance readings were collected every 1 s by spectrophotometer.
Measurement: IC50 = 44500 nM (pChEMBL 4.349999904632568)
Descriptors: MW 312.37, ALogP 1.73, HBA 3, HBD 3, PSA 87.46, QED 0.73