Daunorubicin HCl

Names

[ Name ]:
Daunorubicin HCl

[Synonym ]:
(8S,10S)-8-Acetyl-10-[(3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione Hydrochloride
DAUNOBLASTINE
Daunorubicin hydrochloride
(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside hydrochloride
daunoblastin
(1S,3S)-3-Acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-tetracenyl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside hydrochloride (1:1)
Daunorubicin HCl
(1S,3S)-3-Acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside hydrochloride (1:1)
(8S-cis)-8-Acetyl-10-[(3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione Hydrochloride
Daunorubicin (Hydrochloride)
(8S,10S)-8-acetyl-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride
(8S,10S)-8-Acetyl-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracen-5,12-dionhydrochlorid
Daunoblastina
(8S,10S)-8-acétyl-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-méthyltétrahydro-2H-pyran-2-yl]oxy}-6,8,11-trihydroxy-1-méthoxy-7,8,9,10-tétrahydrotétracène-5,12-dione chlorhydrate
Rubidomycin hydrochloride
Cerubidine
5,12-Naphthacenedione, 8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S,10S)-, hydrochloride (1:1)
5,12-naphthacenedione, 8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S,10S)-, hydrochloride
ndc0082-4155
Daunomycin, monohydrochloride
(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranoside hydrochloride
DAUNOMYCINE HCL
MFCD00076118
daunorubcin hydrochloride
Daunomycin hydrochloride
Dau hydrochloride
Daunorubicinol hydrochloride
Daunomycin HCl
WP900 HYDROCHLORIDE
EINECS 245-723-4
Ondena
Hydroxydaunorubicin Hydrochloride
Daunorubicin.HCl

Biological Activity

[Description]:

Daunorubicin hydrochloride is a topoisomerase II inhibitor with potent antineoplastic activities.

[Related Catalog]:

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Topoisomerase

Natural Products >> Quinones

Research Areas >> Cancer

[Target]

Topoisomerase II

[In Vitro]

The mean IC50 value is 0.04 μM for Daunorubicin (Dnr) in Molt-4 cells. Daunorubicin belongs to the anthracyclines, a group of cytotoxic chemotherapeutics. The cytotoxic effects of anthracyclines are caused by DNA intercalation and the ability to interfere with DNA transcription and replication by inhibiting Topoisomerase II as well as by producing reactive oxygen species[2] Daunorubicin inhibits of both DNA and RNA syntheses in HeLa cells over a concentration range of 0.2 through 2 μM. The IC50 value is 0.4 μM for Daunorubicin (Dnr) in human pancreatic cell line L3.6[3].

[In Vivo]

Urinary protein excretion, serum creatinine, and blood urea nitrogen (BUN) level are significantly increased in group Daunorubicin (3 mg/kg, i.v.) compared with those in group Control. Administration of Daunorubicin (DNR) causes a significant increase in malondialdehyde (MDA) level in renal tissue compared with that in the control group[4].

[Cell Assay]

The chemosensitivity to Daunorubicin is assessed using the MTT assay. In brief, the 96 well plates are set up with cells at the initial density of 2×105 cells/mL and are incubated at 37°C for 72 h in an atmosphere of 5% CO2 in the absence and presence of nine different concentrations of Daunorubicin (Dnr) or Dox ranging from 1.90 to 0.007 μM in triplicate. After incubation, 10 μL of MTT solution (5 mg/mL tetrazolium salt) is added to each well and the plates are incubated for a further 4 h at 37°C. The formazan salt crystals are dissolved by adding 100 μL 10% SDS in 10 mM HCl solution and incubating over night at 37°C. The absorbance is measured at 540 nm with a reference at 650 nm by a 96-well enzyme-linked immunosorbent assay (ELISA) plate reader. Chemosensitivity is expressed as the IC50, which is the concentration of drug causing 50% cell survival compare to control cells grown without drug. Calculations are carried out using Microsoft Excel[2].

[Animal admin]

Rat[4] Eight-week-old male Sprague-Dawley rats are used. The animals are quarantined and acclimatized for the additional 2 weeks prior to the initiation of the experiments. On day 0, each animal receives a single intravenous injection of Daunorubicin at a dose of 3 mg/kg (i.v.). Daunorubicin is administered in three equal injections at 48 h intervals for a period of one week to achieve an accumulative dose of 9 mg/kg, which is well documented to produce cardiotoxicity and nephrotoxicity. Age-matched rats are injected with corresponding volumes of 0.9% NaCl and used as a control (group Control;n=5). Twenty-two DNR-treated rats are randomly divided into two groups and received oral administration of Telmisartan (10 mg/kg/day; group Daunorubicin+Telmisartan; n=10) or vehicle (group Daunorubicin; n=12). The dose of Telmisartan is chosen on the basis of a previous report. Administration of Telmisartan is started on the same day as Daunorubicin administration and continued for 5 additional weeks after cessation of Daunorubicin administration (6 weeks total period). This duration of study is chosen on the basis of previous reports. On day 41, rats are placed individually in metabolic cages for 24-h urine collections for the measurement of protein concentrations and body weight (BW) is measured. After the end of the study period (6 weeks), rats are sacrificed and kidney tissue is harvested for semi-quantitative immunoblotting and immunohistochemical studies.

[References]

[1]. Lehmann M, et al. Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test. Environ Mol Mutagen. 2004;43(4):250-7.

[2]. Svensson SP, et al. Melanin inhibits cytotoxic effects of Doxorubicin and Daunorubicin in MOLT 4 cells. Pigment Cell Res. 2003 Aug;16(4):351-4

[3]. Gervasoni JE Jr, et al. An effective in vitro antitumor response against human pancreatic carcinoma with paclitaxel and Daunorubicin by induction of both necrosis and apoptosis. Anticancer Res. 2004 Sep-Oct;24(5A):2617-26

[4]. Arozal W, et al. Telmisartan prevents the progression of renal injury in daunorubicin rats with the alteration of angiotensin II and endothelin-1 receptor expression associated with its PPAR-γ agonist actions. Toxicology. 2011 Jan 11;279(1-3):91-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
770ºC at 760 mmHg

[ Melting Point ]:
188 - 190ºC

[ Molecular Formula ]:
C₂₇H₃₀ClNO₁₀

[ Molecular Weight ]:
563.981

[ Flash Point ]:
419.5ºC

[ Exact Mass ]:
563.155823

[ PSA ]:
185.84000

[ LogP ]:
2.53120

[ Vapour Pressure ]:
6.99E-26mmHg at 25°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HB7878000

CHEMICAL NAME :: Daunomycin, hydrochloride

CAS REGISTRY NUMBER :: 23541-50-6

LAST UPDATED :: 199806

DATA ITEMS CITED :: 27

MOLECULAR FORMULA :: C27-H29-N-O10.Cl-H

MOLECULAR WEIGHT :: 564.03

WISWESSER LINE NOTATION :: L E6 C666 BV MVT&&&J DQ HV1 HQ KQ RO1 FO- FT6OTJ B1 CQ DZ &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 :: 290 mg/kg

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

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14300 ug/kg

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

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 33200 ug/kg

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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14300 ug/kg

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

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 27900 ug/kg

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 205 mg/kg

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

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3050 ug/kg

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

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 28800 ug/kg

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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 50 mg/kg

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

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 23300 ug/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 375 mg/kg/5D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 11500 ug/kg/5D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 50 mg/kg/5D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 43500 ug/kg/5D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: Specific locus test

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - mouse Liver

DOSE/DURATION :: 17 mg/L

REFERENCE :: AMOKAG Acta Medicia Okayama. (Okayama Univ. Medical School, Okayama, Japan) V.27 1973- Volume(issue)/page/year: 33,149,1979 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4586 No. of Facilities: 49 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 881 (estimated) No. of Female Employees: 459 (estimated)

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H334-H351

[ Precautionary Statements ]:
P261-P281-P301 + P310-P342 + P311

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R22;R40;R42/43

[ Safety Phrases ]:
S22-S36/37-S45

[ RIDADR ]:
UN 2811

[ WGK Germany ]:
3

[ RTECS ]:
HB7878000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2932999099

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2932999099

[ Summary ]:
2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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