Synonym
Dihydrodigoxin; 20,22-Dihydrodigoxin;
IUPAC/Chemical Name
(S)-4-((3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-(((2R,4S,5S,6R)-5-(((2S,4S,5S,6R)-5-(((2S,4S,5S,6R)-4,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-2,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-12,14-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)dihydrofuran-2(3H)-one
InChi Key
VEWZDADDWHCQJR-LODAONNOSA-N
InChi Code
InChI=1S/C42H68O14/c1-20-36(48)29(43)16-35(51-20)54-37-22(3)55-40(5,18-31(37)45)56-38-21(2)52-34(17-30(38)44)53-25-9-11-39(4)24(14-25)7-8-27-28(39)15-32(46)41(6)26(10-12-42(27,41)49)23-13-33(47)50-19-23/h20-32,34-38,43-46,48-49H,7-19H2,1-6H3/t20-,21-,22-,23-,24-,25+,26-,27-,28+,29+,30+,31+,32-,34+,35+,36-,37-,38-,39+,40+,41+,42+/m1/s1
SMILES Code
C[C@H]1O[C@@H](O[C@H]2[C@H](C[C@](O[C@H]3[C@H](C[C@@H](O[C@@H]3C)O[C@H]4CC[C@]5([C@@H](C4)CC[C@@H]6[C@@H]5C[C@H]([C@@]7([C@@H]([C@H]8COC(C8)=O)CC[C@]67O)C)O)C)O)(O[C@@H]2C)C)O)C[C@@H]([C@@H]1O)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Dihydrodigoxin is an extremely weak basic (essentially neutral) compound (based on its pKa).
In vitro activity:
Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug.
Reference: Pac Symp Biocomput. 2018;23:56-67. https://pubmed.ncbi.nlm.nih.gov/29218869/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
796.99
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Mallory EK, Acharya A, Rensi SE, Turnbaugh PJ, Bright RA, Altman RB. Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome. Pac Symp Biocomput. 2018;23:56-67. PMID: 29218869; PMCID: PMC5771676.
2. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, Littman DR. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature. 2011 Apr 28;472(7344):486-90. doi: 10.1038/nature09978. Epub 2011 Mar 27. PMID: 21441909; PMCID: PMC3172133.
In vitro protocol:
1. Mallory EK, Acharya A, Rensi SE, Turnbaugh PJ, Bright RA, Altman RB. Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome. Pac Symp Biocomput. 2018;23:56-67. PMID: 29218869; PMCID: PMC5771676.
2. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, Littman DR. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature. 2011 Apr 28;472(7344):486-90. doi: 10.1038/nature09978. Epub 2011 Mar 27. PMID: 21441909; PMCID: PMC3172133.
1: Butler VP Jr, Tse-Eng D, Lindenbraum J, Kalman SM, Preibisz JJ, Rund DG, Wissel PS. The development and application of a radioimmunoassay for dihydrodigoxin, a digoxin metabolite. J Pharmacol Exp Ther. 1982 Apr;221(1):123-31. PMID: 7062278.
2: Heinz N, Flasch H. Comparison of the pharmacokinetics of digoxin and dihydrodigoxin in cats in single-dose studies. Naunyn Schmiedebergs Arch Pharmacol. 1978 Jun;303(2):181-7. doi: 10.1007/BF00508066. PMID: 673023.
3: Greenwood H, Snedden W, Hayward RP, Landon J. The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy. Clin Chim Acta. 1975 Jul 23;62(2):213-24. doi: 10.1016/0009-8981(75)90230-2. PMID: 1170963.
4: Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, Littman DR. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature. 2011 Apr 28;472(7344):486-90. doi: 10.1038/nature09978. Epub 2011 Mar 27. PMID: 21441909; PMCID: PMC3172133.
5: Watson E, Clark DR, Kalman SM. Identification by gas chromatography-mass spectroscopy of dihydrodigoxin--a metabolite of digoxin in man. J Pharmacol Exp Ther. 1973 Feb;184(2):424-31. PMID: 4688179.
6: BACH EJ, REITER M. THE DIFFERENCE IN VELOCITY BETWEEN THE LETHAL AND INOTROPIC ACTION OF DIHYDRODIGOXIN. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1964 Jul 20;248:437-49. doi: 10.1007/BF00246890. PMID: 14258616.
7: Robertson LW, Chandrasekaran A, Reuning RH, Hui J, Rawal BD. Reduction of digoxin to 20R-dihydrodigoxin by cultures of Eubacterium lentum. Appl Environ Microbiol. 1986 Jun;51(6):1300-3. doi: 10.1128/AEM.51.6.1300-1303.1986. PMID: 3729400; PMCID: PMC239061.
8: Kramer WG, Bathala MS, Reuning RH. Specificity of the digoxin radioimmunoassay with respect to dihydrodigoxin. Res Commun Chem Pathol Pharmacol. 1976 May;14(1):83-8. PMID: 935656.
9: VICK RL, KAHN JB Jr, ACHESON GH. Effects of dihydro-ouabain, dihydrodigoxin and dihydrodigitoxin on the heart-lung preparation of the dog. J Pharmacol Exp Ther. 1957 Nov;121(3):330-9. PMID: 13481854.
10: Kramer WG, Kinnear NL, Morgan HK. Variability among commercially available digoxin radioimmunoassay kits in cross reactivity to dihydrodigoxin. Clin Chem. 1978 Jan;24(1):155-7. PMID: 618648.
