CAS 10592-13-9|doxycycline hydrochloride

Introduction：Basic information about CAS 10592-13-9|doxycycline hydrochloride, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. doxycycline hydrochloride BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Synonyms

Common Name	doxycycline hydrochloride
CAS Number	10592-13-9	Molecular Weight	480.896
Density	1.63 g/cm3	Boiling Point	762.6ºC at 760 mmHg
Molecular Formula	C₂₂H₂₅ClN₂O₈	Melting Point	195-201℃
MSDS	/	Flash Point	415ºC

Names

Name	doxycycline HCl
Synonym	More Synonyms

doxycycline hydrochloride BiologicalActivity

Description	Doxycycline hydrochloride is a tetracycline antibiotic and broad-spectrum metalloproteinase (MMP) inhibitor.
Related Catalog	Research Areas >>Infection
Target	MMP
In Vitro	Doxycycline shows excellent effectiveness and time-dependent characteristics against M. gallisepticum strain S6 in vitro[2]. Osteoblasts exposed to the composite containing 25 μg/mL doxycycline (DOX)/β-cyclodextrin (βCD) has increased cell proliferation (p < 0.05) compared to control osteoblast cultures at all experimental time points, reaching a maximum in the second week. Alkaline phosphatase (AP) activity and collagen secretion levels are also elevated in osteoblasts exposed to the DOX/βCD composite (p < 0.05 vs. controls) and reach a maximum after 14 days[3]. Doxycycline (20 nM) inhibits ECM (extracellular matrix) production and remodeling in both SMC (smooth muscle cell) types of cultures, and synthesis of collagens and isoprenylated proteins in SMC-Ch (a cholesterol-rich diet) is a higher than in SMC-C (a standard diet)[4].
In Vivo	In heterozygous (HT) Col3a1 knockout mice, after 3 months of treatment with doxycycline or placebo, 9-month-old HT or wild-type (WT) mice are subjected to surgical stressing of the aorta. A 3-fold increase in stress-induced aortic lesions found in untreated HT mice 1 week after intervention (cumulative score 4.5±0.87 versus 1.3±0.34 in WT, p<0.001) is fully prevented in the doxycycline (25 or 100 mg/kg, p.o.)-treated group (1.1±0.56)[1].
Kinase Assay	Gelatin (0.1% (w/v) is added to standard LaemmLi acrylamide polymerization mixture. Tissue extract is mixed 1:2 with sample buffer [250 mM Tris-Cl pH 6.8, 10% (w/v) SDS, 20% (v/v) glycerol, 0.005% (w/v) bromphenol blue]. Serum is diluted 1:10 with electrophoresis buffer (2.5 mM Tris, 20 mM glycine, 0.005% SDS) and mixed 1:2 with sample buffer. Twenty μLs are loaded after 10-min incubation at room temperature without boiling. After electrophoresis at 90 V, the gels are soaked in 2.5% (w/v) Triton X-100, incubated 2 to 3 days at 37°C in gelatin digestion buffer [50 mM Tris-Cl, pH 8.0, 8 mM CaCl2, 10 mM ZnSO2, 0.02% (w/v) NaN3], stained in 0.05% Coomassie blue R-250 in acetic acid/methanol/water (1:4.5:4.5 by volume), destained in 10% acetic acid and 5% methanol, and scanned for lysis band intensity. The lysis band intensity is proportional to gelatinase activity and is quantified densitometrically by using One-Dimensional Scan software. The result, a number between 0.07 and 3.75, is normalized to the protein content by dividing the densitometry result with the relative optical density from the BCA protein assay kit result. The result is used for the analysis as the arbitrary unit. For the total MMP activity results of lysis bands of pro-MMP-9, active MMP-9, pro-MMP-2, and active MMP-2 are added. A protein size marker is used to determine the correct size.
Cell Assay	All in vitro treatments are performed in SMC cultures at 90% confluence, when ECM synthesis in SMC starts to be evident. Doxycycline (20 nM) is diluted in culture medium at a concentration of 10 μg/mL (20 nM), at which no toxicity or variation in primary cultured SMC proliferation has been reported, as well as in other cell lines and the incubation time is 48 h. SMC-C and SMC-Ch are seeded at equal cell density in 6-well plates and, when confluence reaches 90%, 1 mL culture medium is added to each well containing 3.7×104 Bq L-[5-H3]-proline (9.62×1011 Bq/mmol). After 48 h incubation, cells are lysed with 0.5 mL 0.5 mol/L NaOH for 1 h. The resulting solution is neutralized with an equal amount of 0.5 mol/L HCl, and 50 μL are used to measure total proteins with the Bradford method. One volume of 10% TCA is added to the remaining 250 μL and centrifuged at 13,000 g for 15 min at 4°C. The resulting precipitate is dissolved in 100 μL 0.2 mol/L NaOH, and then neutralized with 1 mol/L HCl. The solution is incubated with collagenase buffer (Tris-HCl, pH 7.6 20 mM, and CaCl2 250 mM final concentration) and 10 units of collagenase at 37°C overnight. Then, 150 μL 10% TCA are added and centrifuged at 13000 g for 15 min at 4°C. The resulting supernatant is added to 4 mL of scintillation fluid and the radioactivity is measured in a liquid scintillation counter LS 600 TA.
Animal Admin	Two groups of 6-month-old female heterozygous (HT) Col3a1 knockout mice are treated for 3 months with doxycycline. Treatment is provided with food containing 200 or 800 mg/kg of doxycycline. Because preliminary measured food intake of these mice is averaged at 3.5 g/day and the average body weight of animals is 25 g, the average drug dose for low- and high-dose groups is 25 (Doxy25) or 100 (Doxy100) mg/kg per day, respectively. Untreated (wild type) WT and HT mice are maintained on a regular diet (NIH-07 mouse/rat diet) and served as controls. After 3 months, under general inhalation anesthesia (2% of isoflurane in oxygen) and aseptic conditions, the abdominal aortas are surgically exposed and stressed by the following technique: the blood flow is stopped by occluding the abdominal aorta against the spinal column with a sterile cotton-tip applicator pressed at the level of the renal arteries. After 30 s a second applicator is pressed at the level of iliac bifurcation and the first applicator is abruptly released, followed by release of the second applicator. The abdominal incision is sutured closed, and mice are returned to home cages. The treatment is continued after the intervention. One week after intervention mice are euthanized by an overdose of isoflurane. Blood is collected, and aortas and segments of colon and skin are harvested.
References	[1]. 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. [2]. Zhang N, et al. The PK/PD Interactions of Doxycycline against Mycoplasma gallisepticum. Front Microbiol. 2016 May 4;7:653. [3]. Trajano VC, et al. Osteogenic activity of cyclodextrin-encapsulated doxycycline in a calcium phosphate PCL and PLGA composite. Mater Sci Eng C Mater Biol Appl. 2016 Jul 1;64:370-5. [4]. Palomino-Morales R, et al. Inhibition of extracellular matrix production and remodeling by doxycycline in smooth muscle cells. J Pharmacol Sci. 2016 Mar 25. Epub ahead of print

Chemical & Physical Properties

Density	1.63 g/cm3
Boiling Point	762.6ºC at 760 mmHg
Melting Point	195-201℃
Molecular Formula	C₂₂H₂₅ClN₂O₈
Molecular Weight	480.896
Flash Point	415ºC
Exact Mass	480.129944
PSA	181.62000
LogP	1.15470
InChIKey	PTNZGHXUZDHMIQ-CVHRZJFOSA-N
SMILES	CC1c2cccc(O)c2C(O)=C2C(=O)C3(O)C(O)=C(C(N)=O)C(=O)C(N(C)C)C3C(O)C21.Cl
Storage condition	0-6°C
Water Solubility	H2O: 50 mg/mL, clear, yellow-green

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QI8925000

CHEMICAL NAME :: 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, monohydrochloride

CAS REGISTRY NUMBER :: 10592-13-9

LAST UPDATED :: 199806

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C22-H24-N2-O8.Cl-H

MOLECULAR WEIGHT :: 480.94

WISWESSER LINE NOTATION :: L E6 C666 BV FV CU GUTTT&J DQ EQ GVZ HQ IN1&1 MQ M1 RQ &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1700 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,1447,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 714 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,840,1995

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 700 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,1447,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 137 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,1447,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1890 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,505,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 179 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,714,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 700 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,1447,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 201 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,840,1995

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,714,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >100 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,840,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 26 mg/kg/13W-I

TOXIC EFFECTS :: Cardiac - changes in heart weight Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 129,214,1994 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intrauterine

DOSE :: 50 mg/kg

SEX/DURATION :: female 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 29,553,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intrauterine

DOSE :: 20 mg/kg

SEX/DURATION :: female 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 29,561,1984

Safety Information

Hazard Codes	Xn: Harmful;Xi: Irritant;
Risk Phrases	R22
Safety Phrases	26-36/37
WGK Germany	3
HS Code	29413000

Customs

HS Code	29413000

Synonyms

Doxylin

samecin

(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride (1:1)

(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide hydrochloride

liomycin

EINECS 234-198-7

(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide Monohydrochloride

Doxycycline (hydrochloride)

Doxycycline HCl

tecacin

DOXYCYCLINE

doxycycline hyclate

doxycycline hydrochloride

ecodox

MFCD03427564

6-deoxy-5-oxytetracycline hydrochloride

novadox

retens

DOXYCYCLINEHCL

HYDRAMYCIN

doxy-ii

a-6-Deoxy-5-hydroxytetracycline Hydrochloride

mespafin

2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, (4S,4aR,5S,5aR,6R,12aS)-, hydrochloride (1:1)

(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide hydrochloride (1:1)

(4S-(4a,4aa,5a,5aa,6a,12aa))-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide Monohydrochloride

midoxin

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