afegostat [Ligand Id: 7410] activity data from GtoPdb and ChEMBL

Click here for a description of the charts and data table

Please tell us if you are using this feature and what you think!

ChEMBL ligand: CHEMBL206468 (Afegostat, Isofagomine)
  • Alpha-galactosidase in Coffea arabica [ChEMBL: CHEMBL5217] [UniProtKB: Q42656]
There should be some charts here, you may need to enable JavaScript!
  • Alpha-glucosidase in Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) [ChEMBL: CHEMBL3784909] [UniProtKB: Q9C0Y4]
There should be some charts here, you may need to enable JavaScript!
There should be some charts here, you may need to enable JavaScript!
There should be some charts here, you may need to enable JavaScript!
There should be some charts here, you may need to enable JavaScript!
  • Glycogen phosphorylase, liver form in Human [ChEMBL: CHEMBL2568] [UniProtKB: P06737]
  • Glycogen phosphorylase, liver form in Rat [ChEMBL: CHEMBL3239] [UniProtKB: P09811]
There should be some charts here, you may need to enable JavaScript!
  • Glycogen phosphorylase, muscle form in Rabbit [ChEMBL: CHEMBL4696] [UniProtKB: P00489]
There should be some charts here, you may need to enable JavaScript!
There should be some charts here, you may need to enable JavaScript!
  • glucosylceramidase beta/Lysosomal acid glucosylceramidase in Human [ChEMBL: CHEMBL2179] [GtoPdb: 2978] [UniProtKB: P04062]
There should be some charts here, you may need to enable JavaScript!
DB Assay description Assay Type Standard value Standard parameter Original value Original units Original parameter Reference
Alpha-galactosidase in Coffea arabica (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5217] [UniProtKB: Q42656]
ChEMBL Inhibition of green coffee bean alpha-galactosidase B 4 pIC50 >100000 nM IC50 Medchemcomm (2016) 7: 365-370
Alpha-glucosidase in Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3784909] [UniProtKB: Q9C0Y4]
ChEMBL Inhibition of Saccharomyces cerevisiae alpha glucosidase B 4 pIC50 >100000 nM IC50 Medchemcomm (2016) 7: 365-370
Beta-galactosidase in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2522] [UniProtKB: P16278]
ChEMBL Inhibition of beta-galactosidase derived from human peripheral blood mononuclear cell lysate using 4-methylumbelliferyl beta-D-galactopyranoside as substrate after 2 hrs by fluorescence analysis B 5 pIC50 >10000 nM IC50 Bioorg Med Chem (2018) 26: 5462-5469 [PMID:30270003]
Beta-galactosidase in Bovine (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3482] [UniProtKB: Q58D55]
ChEMBL Inhibition of bovine liver beta-galactosidase assessed as production of p-nitrophenol by spectrophotometry B 5.44 pIC50 3600 nM IC50 Bioorg Med Chem (2011) 19: 3558-3568 [PMID:21546253]
Beta-galactosidase in Escherichia coli (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4603] [UniProtKB: P00722]
ChEMBL Inhibition of Escherichia coli beta-galactosidase B 4 pIC50 >100000 nM IC50 Medchemcomm (2016) 7: 365-370
Beta-glucosidase in Agrobacterium tumefaciens (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4663] [UniProtKB: P27034]
ChEMBL Inhibition of Agrobacterium sp. beta-glucosidase B 8.15 pKi 7 nM Ki Bioorg Med Chem Lett (2006) 16: 2067-2070 [PMID:16481162]
Beta-glucosidase in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3761] [UniProtKB: Q9HCG7]
ChEMBL Inhibition of beta-glucosidase derived from human peripheral blood mononuclear cell lysate using 4-methylumbelliferyl beta-D-glucopyranoside as substrate after 2 hrs by fluorescence analysis B 7.7 pIC50 20 nM IC50 Bioorg Med Chem (2018) 26: 5462-5469 [PMID:30270003]
Glucosylceramidase in Bovine (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1275219] [UniProtKB: Q2KHZ8]
ChEMBL Inhibition of bovine liver beta-glucosidase assessed as production of 4-methylumbelliferone using 4-methylumbelliferyl beta-D-glucoside as substrate by spectrophotometry B 4.51 pIC50 31000 nM IC50 Bioorg Med Chem (2011) 19: 3558-3568 [PMID:21546253]
Glycogen phosphorylase, liver form in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2568] [UniProtKB: P06737]
ChEMBL Inhibition of liver glycogen phosphorylase A B 6.15 pIC50 700 nM IC50 Bioorg Med Chem (2008) 16: 7330-7336 [PMID:18595718]
ChEMBL Inhibition of phosphorylated form of pig liver glycogen phosphorylase B 6.17 pIC50 670 nM IC50 J Med Chem (2006) 49: 5687-5701 [PMID:16970395]
Glycogen phosphorylase, liver form in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3239] [UniProtKB: P09811]
ChEMBL Inhibition of phosphorylated form of rat liver glycogen phosphorylase B 6.17 pIC50 680 nM IC50 J Med Chem (2006) 49: 5687-5701 [PMID:16970395]
Glycogen phosphorylase, muscle form in Rabbit (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4696] [UniProtKB: P00489]
ChEMBL Inhibition of non-phosphorylated form of rabbit muscle glycogen phosphorylase in presence of phosphate B 5.28 pKi 5200 nM Ki J Med Chem (2006) 49: 5687-5701 [PMID:16970395]
ChEMBL Inhibition of non-phosphorylated form of rabbit muscle glycogen phosphorylase B 5.92 pIC50 1210 nM IC50 J Med Chem (2006) 49: 5687-5701 [PMID:16970395]
ChEMBL Inhibition of phosphorylated form of rabbit muscle glycogen phosphorylase B 6.12 pIC50 760 nM IC50 J Med Chem (2006) 49: 5687-5701 [PMID:16970395]
Lactase/phlorizin hydrolase in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3389] [UniProtKB: Q02401]
ChEMBL Inhibition of rat intestinal lactase assessed as production of p-nitrophenol by spectrophotometry B 6.92 pIC50 120 nM IC50 Bioorg Med Chem (2011) 19: 3558-3568 [PMID:21546253]
glucosylceramidase beta/Lysosomal acid glucosylceramidase in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2179] [GtoPdb: 2978] [UniProtKB: P04062]
ChEMBL Competitive inhibition of human recombinant imiglucerase using 4-MU-beta-D-Glu as substrate at pH 5.2 after 30 mins by fluorometry based Lineweaver-Burk plot analysis B 6.66 pKi 220 nM Ki Medchemcomm (2016) 7: 365-370
ChEMBL Assay for Determination of Ki Values for Inhibition of GCase Activity: Various concentrations of test compounds were prepared in DMSO and then diluted into buffer consisting of 50 mM sodium phosphate 0.25% w/v sodium taurodexoycholate, pH 7.0. GCase enzyme (Cerezyme®, recombinant human GCase obtained from R&D Systems) was diluted in the same buffer to 0.143 nM. The reaction solution consisted of 25 μL of 6 mM 4-methylumbelliferone-β-D glucopyranoside in 10% DMSO in the same buffer, 12.5 μL of enzyme and 12.5 μL of various concentrations of test compound diluted in buffer. The final concentrations in the reaction were 0.036 nM GCase, 3 mM 4-methylumbelliferone-β-D glucopyranoside, and various concentrations of inhibitor. The reaction was initiated by addition of enzyme and allowed to proceed for 20 min at 37° C. to assess GCase activity. Reactions were stopped by the addition of an equal volume (50 μL) of 0.5 M NaOH, 0.3 M glycine, pH 10.5. Fluorescence was measured on a Biotek Synergy H4 plate reader using a setting of 10 measurements per data point at wavelengths of 365 nm for excitation and 450 nm for emission. Incubations without added enzyme or added inhibitors were used to define no enzyme activity and maximal enzyme activity, respectively. IC50 values were determined by fitting the data to a log[inhibitor concentration] versus response curve using GraphPad Prism. IC50 values were calculated as the concentration of inhibitor required to inhibit GCase activity by 50%. Ki values were determined from the IC50 values by employing the Cheng-Prusoff equation using a GCase Km of 7.9 mM for 4-methylumbelliferone-β-D glucopyranoside at pH 7.0. The compounds of the invention tested exhibit Ki values for inhibition of GCase in the range 0.1 nM-50 μM. B 8.77 pKi 1.7 nM Ki US-10081601-B2. Glucocerebrosidase modulators and uses thereof (2018)
ChEMBL Inhibition Assay: Various concentrations of test compounds were prepared in DMSO and then diluted into buffer consisting of 50 mM sodium phosphate 0.25% w/v sodium taurodexoycholate, pH 7.0. GCase enzyme (Cerezyme®, recombinant human GCase obtained from R&D Systems) was diluted in the same buffer to 0.143 nM. The reaction solution consisted of 25 μL of 6 mM 4-methylumbelliferone-β-D glucopyranoside in 10% DMSO in the same buffer, 12.5 μL of enzyme and 12.5 μL of various concentrations of test compound diluted in buffer. The final concentrations in the reaction were 0.036 nM GCase, 3 mM 4-methylumbelliferone-β-D glucopyranoside, and various concentrations of inhibitor. The reaction was initiated by addition of enzyme and allowed to proceed for 20 min at 37° C. to assess GCase activity. Reactions were stopped by the addition of an equal volume (50 μL) of 0.5 M NaOH, 0.3 M glycine, pH 10.5. Fluorescence was measured on a Biotek Synergy H4 plate reader using a setting of 10 measurements per data point at wavelengths of 365 nm for excitation and 450 nm for emission. Incubations without added enzyme or added inhibitors were used to define no enzyme activity and maximal enzyme activity, respectively. IC50 values were determined by fitting the data to a log [inhibitor concentration] versus response curve using GraphPad Prism. IC50 values were calculated as the concentration of inhibitor required to inhibit GCase activity by 50%. Ki values were determined from the IC50 values by employing the Cheng-Prusoff equation using a GCase Km of 7.9 mM for 4-methylumbelliferone-β-D glucopyranoside at pH 7.0. B 8.77 pKi 1.7 nM Ki US-9796680-B2. Glucocerebrosidase modulators and uses thereof (2017)
ChEMBL Inhibition of human recombinant imiglucerase using 4-MU-beta-D-Glu as substrate at pH 7.0 after 30 mins by fluorometric analysis B 5.82 pIC50 1520 nM IC50 Medchemcomm (2016) 7: 365-370
ChEMBL Inhibition of human recombinant imiglucerase using 4-MU-beta-D-Glu as substrate at pH 5.2 after 30 mins by fluorometric analysis B 6.13 pIC50 740 nM IC50 Medchemcomm (2016) 7: 365-370
ChEMBL Inhibition of GCase in patient derived fibroblast cells using 5'pentafluorobenzoylaminofluorescein-di-beta-D-glucoside as substrate assessed as substrate hydrolysis by FACS analysis B 6.39 pIC50 410 nM IC50 Bioorg Med Chem Lett (2023) 81: 129130-129130 [PMID:36640928]
ChEMBL Inhibition of GCase N370S GBA mutant in patient derived fibroblast cells using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate incubated for 5 days by fluorescence based analysis B 6.39 pIC50 410 nM IC50 Bioorg Med Chem Lett (2023) 96: 129531-129531 [PMID:37866711]
ChEMBL Inhibition of recombinant GCase (unknown origin) using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate at pH 4.5 B 6.64 pIC50 230 nM IC50 Bioorg Med Chem Lett (2023) 81: 129130-129130 [PMID:36640928]
ChEMBL Inhibition of glucocerebrosidase N370S mutant in spleen homogenates of patient with Gaucher disease using resorufin-beta-D-glucopyranoside as substrate after 20 mins fluorescence assay B 7.1 pIC50 80 nM IC50 Medchemcomm (2012) 3: 56-60 [PMID:22606365]
ChEMBL Inhibition of human lysosome beta-glucosidase assessed as production of 4-methylumbelliferone using 4-methylumbelliferyl beta-D-glucoside as substrate by spectrophotometry B 7.2 pIC50 63 nM IC50 Bioorg Med Chem (2011) 19: 3558-3568 [PMID:21546253]
ChEMBL Inhibition of human lysosomal beta-glucosidase B 7.22 pIC50 60 nM IC50 Bioorg Med Chem (2008) 16: 7330-7336 [PMID:18595718]
ChEMBL Inhibition of GCase assessed as 4-methylumbelliferone release assay after 30 mins by fluorimetry B 7.23 pIC50 59 nM IC50 Nat Chem Biol (2007) 3: 101-107 [PMID:17187079]
ChEMBL Inhibition of human GCase assessed as reduction of 4-methylumbelliferone liberation using 4-methylumbelliferyl-beta-glucopyranoside as substrate preincubated with enzyme for 10 mins followed by substrate addition by fluorescence spectrophotometry B 7.4 pIC50 40 nM IC50 Eur J Med Chem (2022) 238: 114499-114499 [PMID:35675756]
ChEMBL Assay for Determination of Ki Values for Inhibition of GCase Activity: Various concentrations of test compounds were prepared in DMSO and then diluted into buffer consisting of 50 mM sodium phosphate 0.25% w/v sodium taurodexoycholate, pH 7.0. GCase enzyme (Cerezyme®, recombinant human GCase obtained from R&D Systems) was diluted in the same buffer to 0.143 nM. The reaction solution consisted of 25 μL of 6 mM 4-methylumbelliferone-β-D glucopyranoside in 10% DMSO in the same buffer, 12.5 μL of enzyme and 12.5 μL of various concentrations of test compound diluted in buffer. The final concentrations in the reaction were 0.036 nM GCase, 3 mM 4-methylumbelliferone-β-D glucopyranoside, and various concentrations of inhibitor. The reaction was initiated by addition of enzyme and allowed to proceed for 20 min at 37° C. to assess GCase activity. Reactions were stopped by the addition of an equal volume (50 μL) of 0.5 M NaOH, 0.3 M glycine, pH 10.5. Fluorescence was measured on a Biotek Synergy H4 plate reader using a setting of 10 measurements per data point at wavelengths of 365 nm for excitation and 450 nm for emission. Incubations without added enzyme or added inhibitors were used to define no enzyme activity and maximal enzyme activity, respectively. IC50 values were determined by fitting the data to a log[inhibitor concentration] versus response curve using GraphPad Prism. IC50 values were calculated as the concentration of inhibitor required to inhibit GCase activity by 50%. Ki values were determined from the IC50 values by employing the Cheng-Prusoff equation using a GCase Km of 7.9 mM for 4-methylumbelliferone-β-D glucopyranoside at pH 7.0. The compounds of the invention tested exhibit Ki values for inhibition of GCase in the range 0.1 nM-50 μM. B 8.09 pIC50 8.2 nM IC50 US-10081601-B2. Glucocerebrosidase modulators and uses thereof (2018)
ChEMBL Inhibition Assay: Various concentrations of test compounds were prepared in DMSO and then diluted into buffer consisting of 50 mM sodium phosphate 0.25% w/v sodium taurodexoycholate, pH 7.0. GCase enzyme (Cerezyme®, recombinant human GCase obtained from R&D Systems) was diluted in the same buffer to 0.143 nM. The reaction solution consisted of 25 μL of 6 mM 4-methylumbelliferone-β-D glucopyranoside in 10% DMSO in the same buffer, 12.5 μL of enzyme and 12.5 μL of various concentrations of test compound diluted in buffer. The final concentrations in the reaction were 0.036 nM GCase, 3 mM 4-methylumbelliferone-β-D glucopyranoside, and various concentrations of inhibitor. The reaction was initiated by addition of enzyme and allowed to proceed for 20 min at 37° C. to assess GCase activity. Reactions were stopped by the addition of an equal volume (50 μL) of 0.5 M NaOH, 0.3 M glycine, pH 10.5. Fluorescence was measured on a Biotek Synergy H4 plate reader using a setting of 10 measurements per data point at wavelengths of 365 nm for excitation and 450 nm for emission. Incubations without added enzyme or added inhibitors were used to define no enzyme activity and maximal enzyme activity, respectively. IC50 values were determined by fitting the data to a log [inhibitor concentration] versus response curve using GraphPad Prism. IC50 values were calculated as the concentration of inhibitor required to inhibit GCase activity by 50%. Ki values were determined from the IC50 values by employing the Cheng-Prusoff equation using a GCase Km of 7.9 mM for 4-methylumbelliferone-β-D glucopyranoside at pH 7.0. B 8.09 pIC50 8.2 nM IC50 US-9796680-B2. Glucocerebrosidase modulators and uses thereof (2017)
ChEMBL Chaperone activity at GCase N370S GBA mutant in patient derived fibroblast cell assessed as GCase level incubated for 5 days by immunocytochemistry assay B 6.41 pEC50 390 nM EC50 Bioorg Med Chem Lett (2023) 81: 129130-129130 [PMID:36640928]
ChEMBL Chaperone activity at GCase N370S GBA mutant in patient derived fibroblast cell using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate assessed as substrate cleavage by measuring concentration required for maximal response incubated for 5 days by fluorescence based assay B 6.52 pEC50 300 nM EC50 Bioorg Med Chem Lett (2023) 81: 129130-129130 [PMID:36640928]
ChEMBL Chaperone activity at GCase N370S GBA mutant in patient derived fibroblast cells using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate incubated for 5 days by fluorescence based analysis B 6.52 pEC50 300 nM EC50 Bioorg Med Chem Lett (2023) 96: 129531-129531 [PMID:37866711]

ChEMBL data shown on this page come from version 36:

Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]