Mitoxantrone 2HCl

Names

[ Name ]:
Mitoxantrone 2HCl

[Synonym ]:
1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracene-9,10-dione dihydrochloride
Mitoxantrone dihydrochloride
MITOXANTHRONE HYDROCHLORIDE
Mitoxantrone 2HCl
1,4-dihydroxy-5,8-bis({2-[(2-hydroxyéthyl)amino]éthyl}amino)anthracène-9,10-dione dichlorhydrate
MITOZANTRONE
MFCD00242943
1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracen-9,10-diondihydrochlorid
1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione,dihydrochloride
MITOXANTRONE HCl
9,10-anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-, dihydrochloride
Mitoxantrone hydrochloride
Novantron
Onkotrone
UNII-U6USW86RD0
1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthraquinone Dihydrochloride
EINECS 274-619-1
1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-anthraquinone dihydrochloride
novatrone
9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-, hydrochloride (1:2)
NSC-310739
Mitoxantrone (dihydrochloride)

Biological Activity

[Description]:

Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM.

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PKC

Signaling Pathways >> TGF-beta/Smad >> PKC

Research Areas >> Cancer

[Target]

PKC:8.5 μM (IC50)

Topoisomerase II

[In Vitro]

Mitoxantrone inhibits PKC in a competitive manner with respect to histone H1, and its Ki value is 6.3 μM and in a non-competitive manner with respect to phosphatidylserine and ATP[1]. Treatment of B-CLL cells for 48 h with mitoxantrone (0.5 μg/mL) induces a decrease in cell viability. Mitoxantrone induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of mitoxantrone is due to induction of apoptosis[2]. Mitoxantrone shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC50 values of 18 and 196 nM, respectively[3].

[In Vivo]

Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produces a statistically significant number of 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also shows effective antitumor activities and produces a 60% and a 45% ILS, respectively.[4].

[Cell Assay]

The human breast carcinoma cell lines MDA-MB-231 and MCF-7 are seeded in standard 96-well plates. One day after seeding, the culture medium is changed and replaced by medium containing different concentration of Mitoxantrone (10-5 to 5 μM) with or without DHA (30 μM) during 7 days. Viability of cells are measured as a whole by the tetrazolium salt assay[3].

[Animal admin]

Mice: Mitoxantrone is tested for antitumor activity against experimental tumors in mice and the results are compared with those of seven antitumor antibiotics. The drugs are given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. Mitoxantrone is given IP at the optimal dose (1.6 mg/kg/day; as a free base)[4].

[References]

[1]. Takeuchi N, et al. Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. J Biochem. 1992 Dec;112(6):762-7.

[2]. Bellosillo B, et al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.

[3]. Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma Res. 2013 Mar;26(2):193-204.

[4]. Fujimoto S, et al. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
805.7ºC at 760 mmHg

[ Melting Point ]:
203-205ºC

[ Molecular Formula ]:
C₂₂H₃₀Cl₂N₄O₆

[ Molecular Weight ]:
517.403

[ Flash Point ]:
441.1ºC

[ Exact Mass ]:
516.154236

[ PSA ]:
163.18000

[ LogP ]:
2.39260

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CB0386900

CHEMICAL NAME :: Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl )amino)-, dihydrochloride

CAS REGISTRY NUMBER :: 70476-82-3

LAST UPDATED :: 199806

DATA ITEMS CITED :: 29

MOLECULAR FORMULA :: C22-H28-N4-O6.2Cl-H

MOLECULAR WEIGHT :: 517.46

WISWESSER LINE NOTATION :: L C666 BV IVJ DQ GQ KM2M2Q NM2M2Q &GH 2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 4400 ug/kg/30W-I

TOXIC EFFECTS :: Skin and Appendages - nails

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 71 ug/kg/2W-I

TOXIC EFFECTS :: Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage)

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 682 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 :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1640 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 :: 8 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5500 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 :: 4800 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 :: 502 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 :: 16500 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 :: 19700 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 :: 9700 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 :: Intraperitoneal

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1200 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 :: Mammal - dog

DOSE/DURATION :: 375 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 :: Primate - monkey

DOSE/DURATION :: >1 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 :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 125 mg/kg

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

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 310 ng/L

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,1375,1986

Safety Information

[ Symbol ]:

GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H340-H360

[ Precautionary Statements ]:
P201-P280-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;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 ]:
T: Toxic;T+: Very toxic;

[ Risk Phrases ]:
R46;R61

[ Safety Phrases ]:
53-36/37/39-45-22

[ RIDADR ]:
UN 3249

[ WGK Germany ]:
3

[ RTECS ]:
CB5748500

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2914610000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2914610000

[ Summary ]:
2914610000 anthracene-9,10-dione。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。Lowest tariff:5.5%。General tariff:30.0%

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