digitoxin [Ligand Id: 6782] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL254219 (Cristapurat, Crystodigin, CRYSTODIGIN, Digimerck, Digitalin, crystalline, Digitophyllin, Digitoxin, Digitoxina, Digitoxine, Digitoxinum, Glucodigin, Lanatoxin, Nativelle digitaline, NSC-7529, Purpurid, Tradigal) |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| sodium/potassium-transporting ATPase subunit α-1/sodium/potassium-transporting ATPase subunit β-1/sodium/potassium-transporting ATPase subunit α-3/sodium/potassium-transporting ATPase subunit β-2/sodium/potassium-transporting ATPase subunit α-2/sodium/potassium-transporting ATPase subunit β-3/sodium/potassium-transporting ATPase subunit γ/sodium/potassium-transporting ATPase subunit α-4/Sodium/potassium-transporting ATPase in Human (target type: PROTEIN COMPLEX GROUP) [ChEMBL: CHEMBL2095186] [GtoPdb: 833, 837, 835, 838, 834, 839, 2610, 836] [UniProtKB: P05023, P05026, P13637, P14415, P50993, P54709, P54710, Q13733] | ||||||||
| ChEMBL | Inhibition of [3H]- ouabain binding to digitalis receptor | B | 8.1 | pIC50 | 8 | nM | IC50 | J Med Chem (1993) 36: 42-45 [PMID:8421289] |
| sodium/potassium-transporting ATPase subunit α-1/sodium/potassium-transporting ATPase subunit β-1/sodium/potassium-transporting ATPase subunit α-3/sodium/potassium-transporting ATPase subunit β-2/sodium/potassium-transporting ATPase subunit α-2/sodium/potassium-transporting ATPase subunit β-3/sodium/potassium-transporting ATPase subunit γ/sodium/potassium-transporting ATPase subunit α-4 in Dog [GtoPdb: 833, 837, 835, 838, 834, 839, 2610, 836] | ||||||||
| GtoPdb | - | - | 8.1 | pIC50 | 8 | nM | IC50 | J Med Chem (1993) 36: 42-5 [PMID:8421289] |
| Sodium/potassium-transporting ATPase subunit alpha-1 in Dog (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4838] [UniProtKB: P50997] | ||||||||
| ChEMBL | Inhibition of [3H]ouabain binding to Digitalis receptor in dog heart microsomes | B | 8.1 | pIC50 | 8 | nM | IC50 | J Med Chem (1997) 40: 1439-1446 [PMID:9154966] |
| sodium/potassium-transporting ATPase subunit α-1/sodium/potassium-transporting ATPase subunit β-1/Sodium/potassium-transporting ATPase subunit alpha-1/beta-1 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL6066559] [GtoPdb: 833, 837] [UniProtKB: P05023, P05026] | ||||||||
| ChEMBL | Selective Inhibition Assays of Isolated Na,K-ATPase: To screen for isoform selectivity of the digoxin derivatives we compared inhibition of Na,K-ATPase activity of purified detergent-soluble human isoform complexes α1β1FXYD1, α2β1FXYD1, α2β2FXTD1 and α2β3FXYD1. Although all the preparations and assays were conducted with FXYD1 in order to stabilize the complexes, the FXYD1 suffix is omitted in naming of isoform complexes for simplicity.Na,K-ATPase activity of α/βPFXYD1 complexes was measured over one hour at 37° C. in a medium containing 130 mM NaCl, 5 mM KCl, 3 mM MgCl2, 1 mM EGTA, 25 mM Histidine, pH 7.4 and 1 mM ATP using the PiColor Lock gold malachite green assay (Inova Biosciences).The Na,K-ATPase activities were α1β1, 21.5±5.3 μmoles/min/mg; α2β1, 18.7±1.8 μmoles/min/mg, and α2β3, 10.7±1.9 μmoles/min/mg protein. As discussed below, an important kinetic property in relation to inhibition by cardiac glycosides is K0.5 for activation by K: α1β1-1.25±0.05 mM, α2β1-2.7±0.14 mM and α2β3 6.4±0.50 mM, respectively.Selectivity of the compounds for various isolated isoforms of human Na,K-ATPase was determined essentially as described before [Katz, A. et al., J Biol Chem., 2010, 285(25), pp. 19582-19592].ATPase activity assays as well as titrations with NaCl, KCl and vanadate were performed as described in Lifshitz-2007 and Loayza-1998 using PiColorLock malachite green assay (Inova Bioscience). Inhibitor assays were performed as described in Katz-2010. [3H]ouabain binding and K+-[3H]digoxin displacement assays were performed as described in Katz-2010.The percent inhibition VCG/V0 was calculated and Ki values were obtained by fitting the data to the function VCG/V0=Ki/([CG]+Ki)+c (CG stands for cardiac glycoside). Inhibition was estimated in 3-5 separate experiments and average Ki values±standard error of the mean (SEM) were calculated. The ratios Ki α1β1/α2β1, α1β1/α2β2 and α1β1/α2β3 was calculated for each compound. | B | 7.05 | pKi | 89 | nM | Ki | US-10668094-B2. Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure (2020) |
| sodium/potassium-transporting ATPase subunit α-1/sodium/potassium-transporting ATPase subunit β-1 in Dog [GtoPdb: 833, 837] | ||||||||
| GtoPdb | - | - | 8.1 | pIC50 | 8 | nM | IC50 | J Med Chem (1993) 36: 42-5 [PMID:8421289] |
| sodium/potassium-transporting ATPase subunit β-1/sodium/potassium-transporting ATPase subunit α-2/Sodium/potassium-transporting ATPase subunit alpha-2/beta-1 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL6066560] [GtoPdb: 837, 834] [UniProtKB: P05026, P50993] | ||||||||
| ChEMBL | Selective Inhibition Assays of Isolated Na,K-ATPase: To screen for isoform selectivity of the digoxin derivatives we compared inhibition of Na,K-ATPase activity of purified detergent-soluble human isoform complexes α1β1FXYD1, α2β1FXYD1, α2β2FXTD1 and α2β3FXYD1. Although all the preparations and assays were conducted with FXYD1 in order to stabilize the complexes, the FXYD1 suffix is omitted in naming of isoform complexes for simplicity.Na,K-ATPase activity of α/βPFXYD1 complexes was measured over one hour at 37° C. in a medium containing 130 mM NaCl, 5 mM KCl, 3 mM MgCl2, 1 mM EGTA, 25 mM Histidine, pH 7.4 and 1 mM ATP using the PiColor Lock gold malachite green assay (Inova Biosciences).The Na,K-ATPase activities were α1β1, 21.5±5.3 μmoles/min/mg; α2β1, 18.7±1.8 μmoles/min/mg, and α2β3, 10.7±1.9 μmoles/min/mg protein. As discussed below, an important kinetic property in relation to inhibition by cardiac glycosides is K0.5 for activation by K: α1β1-1.25±0.05 mM, α2β1-2.7±0.14 mM and α2β3 6.4±0.50 mM, respectively.Selectivity of the compounds for various isolated isoforms of human Na,K-ATPase was determined essentially as described before [Katz, A. et al., J Biol Chem., 2010, 285(25), pp. 19582-19592].ATPase activity assays as well as titrations with NaCl, KCl and vanadate were performed as described in Lifshitz-2007 and Loayza-1998 using PiColorLock malachite green assay (Inova Bioscience). Inhibitor assays were performed as described in Katz-2010. [3H]ouabain binding and K+-[3H]digoxin displacement assays were performed as described in Katz-2010.The percent inhibition VCG/V0 was calculated and Ki values were obtained by fitting the data to the function VCG/V0=Ki/([CG]+Ki)+c (CG stands for cardiac glycoside). Inhibition was estimated in 3-5 separate experiments and average Ki values±standard error of the mean (SEM) were calculated. The ratios Ki α1β1/α2β1, α1β1/α2β2 and α1β1/α2β3 was calculated for each compound. | B | 7.53 | pKi | 29.5 | nM | Ki | US-10668094-B2. Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure (2020) |
| sodium/potassium-transporting ATPase subunit β-2/sodium/potassium-transporting ATPase subunit α-2/Sodium/potassium-transporting ATPase subunit alpha-2/beta-2 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL6066561] [GtoPdb: 838, 834] [UniProtKB: P14415, P50993] | ||||||||
| ChEMBL | Selective Inhibition Assays of Isolated Na,K-ATPase: To screen for isoform selectivity of the digoxin derivatives we compared inhibition of Na,K-ATPase activity of purified detergent-soluble human isoform complexes α1β1FXYD1, α2β1FXYD1, α2β2FXTD1 and α2β3FXYD1. Although all the preparations and assays were conducted with FXYD1 in order to stabilize the complexes, the FXYD1 suffix is omitted in naming of isoform complexes for simplicity.Na,K-ATPase activity of α/βPFXYD1 complexes was measured over one hour at 37° C. in a medium containing 130 mM NaCl, 5 mM KCl, 3 mM MgCl2, 1 mM EGTA, 25 mM Histidine, pH 7.4 and 1 mM ATP using the PiColor Lock gold malachite green assay (Inova Biosciences).The Na,K-ATPase activities were α1β1, 21.5±5.3 μmoles/min/mg; α2β1, 18.7±1.8 μmoles/min/mg, and α2β3, 10.7±1.9 μmoles/min/mg protein. As discussed below, an important kinetic property in relation to inhibition by cardiac glycosides is K0.5 for activation by K: α1β1-1.25±0.05 mM, α2β1-2.7±0.14 mM and α2β3 6.4±0.50 mM, respectively.Selectivity of the compounds for various isolated isoforms of human Na,K-ATPase was determined essentially as described before [Katz, A. et al., J Biol Chem., 2010, 285(25), pp. 19582-19592].ATPase activity assays as well as titrations with NaCl, KCl and vanadate were performed as described in Lifshitz-2007 and Loayza-1998 using PiColorLock malachite green assay (Inova Bioscience). Inhibitor assays were performed as described in Katz-2010. [3H]ouabain binding and K+-[3H]digoxin displacement assays were performed as described in Katz-2010.The percent inhibition VCG/V0 was calculated and Ki values were obtained by fitting the data to the function VCG/V0=Ki/([CG]+Ki)+c (CG stands for cardiac glycoside). Inhibition was estimated in 3-5 separate experiments and average Ki values±standard error of the mean (SEM) were calculated. The ratios Ki α1β1/α2β1, α1β1/α2β2 and α1β1/α2β3 was calculated for each compound. | B | 7.39 | pKi | 40.7 | nM | Ki | US-10668094-B2. Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure (2020) |
| sodium/potassium-transporting ATPase subunit α-2/sodium/potassium-transporting ATPase subunit β-3/Sodium/potassium-transporting ATPase subunit alpha-2/beta-3 in Human (target type: PROTEIN COMPLEX) [ChEMBL: CHEMBL6066562] [GtoPdb: 834, 839] [UniProtKB: P50993, P54709] | ||||||||
| ChEMBL | Selective Inhibition Assays of Isolated Na,K-ATPase: To screen for isoform selectivity of the digoxin derivatives we compared inhibition of Na,K-ATPase activity of purified detergent-soluble human isoform complexes α1β1FXYD1, α2β1FXYD1, α2β2FXTD1 and α2β3FXYD1. Although all the preparations and assays were conducted with FXYD1 in order to stabilize the complexes, the FXYD1 suffix is omitted in naming of isoform complexes for simplicity.Na,K-ATPase activity of α/βPFXYD1 complexes was measured over one hour at 37° C. in a medium containing 130 mM NaCl, 5 mM KCl, 3 mM MgCl2, 1 mM EGTA, 25 mM Histidine, pH 7.4 and 1 mM ATP using the PiColor Lock gold malachite green assay (Inova Biosciences).The Na,K-ATPase activities were α1β1, 21.5±5.3 μmoles/min/mg; α2β1, 18.7±1.8 μmoles/min/mg, and α2β3, 10.7±1.9 μmoles/min/mg protein. As discussed below, an important kinetic property in relation to inhibition by cardiac glycosides is K0.5 for activation by K: α1β1-1.25±0.05 mM, α2β1-2.7±0.14 mM and α2β3 6.4±0.50 mM, respectively.Selectivity of the compounds for various isolated isoforms of human Na,K-ATPase was determined essentially as described before [Katz, A. et al., J Biol Chem., 2010, 285(25), pp. 19582-19592].ATPase activity assays as well as titrations with NaCl, KCl and vanadate were performed as described in Lifshitz-2007 and Loayza-1998 using PiColorLock malachite green assay (Inova Bioscience). Inhibitor assays were performed as described in Katz-2010. [3H]ouabain binding and K+-[3H]digoxin displacement assays were performed as described in Katz-2010.The percent inhibition VCG/V0 was calculated and Ki values were obtained by fitting the data to the function VCG/V0=Ki/([CG]+Ki)+c (CG stands for cardiac glycoside). Inhibition was estimated in 3-5 separate experiments and average Ki values±standard error of the mean (SEM) were calculated. The ratios Ki α1β1/α2β1, α1β1/α2β2 and α1β1/α2β3 was calculated for each compound. | B | 7.54 | pKi | 28.8 | nM | Ki | US-10668094-B2. Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure (2020) |
| OATP4C1/Solute carrier organic anion transporter family member 4C1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2073690] [GtoPdb: 1227] [UniProtKB: Q6ZQN7] | ||||||||
| ChEMBL | TP_TRANSPORTER: inhibition of Digoxin uptake in OATP4C1-expressing MDCK cells | F | 6.92 | pIC50 | 120 | nM | IC50 | Proc Natl Acad Sci U S A (2004) 101: 3569-3574 [PMID:14993604] |
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]
