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Doxycycline calcium

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Doxycycline calcium Basic information

Product Name:
Doxycycline calcium
Synonyms:
  • DOXYCYCLINECALCIUM
  • 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, calcium salt (1:2), [4S-(4alpha,4aalpha,5alpha,5aalpha,6alpha,12aalpha)]-
  • Doxycycline calcium USP/EP/BP
CAS:
94088-85-4
MF:
C22H26CaN2O8
MW:
486.53
EINECS:
302-088-9
Mol File:
94088-85-4.mol
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Doxycycline calcium Usage And Synthesis

Uses

Doxycycline calcium, an antibiotic, is an orally active and broad-spectrum metalloproteinase (MMP) inhibitor[1]. Doxycycline calcium shows antibacterial activity and anti-cancer cell proliferation activity. Doxycycline calcium can be used to construct gene expression regulation models[1][2][3][4][5].

Veterinary Drugs and Treatments

Although there are no veterinary-approved doxycycline products available, its favorable pharmacokinetic parameters (longer halflife, higher CNS penetration) when compared to either tetracycline HCl or oxytetracycline HCl make it a reasonable choice to use in small animals when a tetracycline is indicated, particularly when a tetracycline is indicated in an azotemic patient.

in vivo

Doxycycline (oral gavage; 200 or 800 mg/kg; once daily; 3 months) calcium reduces MMP-9 activity in untreated HT mice in a dose-dependent manner[3].
Doxycycline calcium and Tetracycline (HY-A0107), act systemically after absorption from the upper gastrointestinal tract. The main advantage of Doxycycline calcium over Tetracycline is its longer activity, and it can be taken twice or once a day. The peak concentration of both agents is similar, but in the case of Doxycycline the time to peak concentration is shorter, and half life is significantly longer[6].

Doxycycline (Dox) calcium is often used as an inducer in molecular biology studies to induce gene expression. In cells or model animals that have constructed tetracycline induced expression systems (Tet-On/Tet-Off systems), the expression of target genes can be precisely controlled by adding or removing Dox[7][8][9][10].
Dose reference for Dox induction[7][8]:
(1) Model animal: male Sprague-Dawley rats
Tet regulatory system: 20-3000 ppm of Dox is supplied in diet.
(2) Model animal: Cags mice
Tet regulatory system: 625 ppm of Dox is supplied in diet.
Induction of Modeling ON-OFF System (Gene expression regulation)[6][7][8]
Background
Doxycycline calcium is often used as an inducer in molecular biology research to induce gene expression. In cells or model animals that have constructed a Tetracycline (Tet; HY-A0107) inducible expression (Tet-ON/Tet-OFF) system, the expression of the target gene can be precisely controlled by adding or removing Doxycycline calcium. Doxycycline calcium can act as an inhibitor of transcriptional activation in the Tetracycline (Tc)-controlled transactivation (tTA) system, and as an inducer of transcriptional activation in the "reverse tTA' system.
Doxycycline and Tetracycline both act systemically after being absorbed by the upper gastrointestinal tract. In comparison, the main advantage of Doxycycline is that it has a longer activity and can be taken twice or once a day. Although the peak concentrations of the two are similar, Doxycycline takes a shorter time to reach peak concentration and has a significantly longer half-life.
Specific Modeling Methods
Rat[8]: Sprague-Dawley rats ? male ? adult middle-aged (12-month-old)
Administration: (for GDNF as targeted gene) 3g/kg (Doxycycline; dietary with regular food) ? po ? once daily for 6 days
Note
(1) Recommend use the recombinant adeno-associated virus (rAAV)-based bicistronic tetracycline (tet)-OFF construct was used for dynamic control of GDNF (target gene) expression during long-term expression[7].
(2) 3 g/kg dietary DOX produced DOX serum levels equivalent to 1mg/ml DOX in drinking water.
Modeling Indicators
Molecular changes: The expression level of the target gene decreases.
Phenotype changes: The positively correlated phenotype corresponding to the target gene is alleviated.
Opposite Product(s): /

Animal Model:6-month-old female Heterozygous Col3a1-deficient (HT) mice[3]
Dosage:200 or 800 mg/kg
Administration:Oral gavage; 200 or 800 mg/kg; once daily; 3 months
Result:Reduced MMP-9 activity in a dose-dependent manner.

IC 50

Tetracycline

References

[1] Eusebio Manchado, et al. A combinatorial strategy for treating KRAS-mutant lung cancer. Nature. 2016 Jun 30;534(7609):647-51. DOI:10.1038/nature18600
[2] Anna-Luisa Luger, et al. Doxycycline Impairs Mitochondrial Function and Protects Human Glioma Cells from Hypoxia-Induced Cell Death: Implications of Using Tet-Inducible Systems. Int J Mol Sci. 2018 May 17;19(5):1504. DOI:10.3390/ijms19051504
[3] Wilfried Briest, et al. Doxycycline ameliorates the susceptibility to aortic lesions in a mouse model for the vascular type of Ehlers-Danlos syndrome. J Pharmacol Exp Ther. 2011 Jun;337(3):621-7. DOI:10.1124/jpet.110.177782
[4] Ethan Ahler, et al. Doxycycline alters metabolism and proliferation of human cell lines. PLoS One. 2013 May 31;8(5):e64561. DOI:10.1371/journal.pone.0064561
[5] Le Zhang, et al. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer. Cell Cycle. 2017 Apr 18;16(8):737-745. DOI:10.1080/15384101.2016.1241929
[6] Manfredsson FP, et al. Tight Long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector. Mol Ther. 2009 Nov;17(11):1857-67. DOI:10.1038/mt.2009.196
[7] Kistner A, et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10933-8. DOI:10.1073/pnas.93.20.10933
[8] Niv Y. Doxycycline in Eradication Therapy of Helicobacter pylori--a Systematic Review and Meta-Analysis. Digestion. 2016;93(2):167-73. DOI:10.1159/000443683

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