CAS 65271-80-9|Mitoxantrone
Introduction：Basic information about CAS 65271-80-9|Mitoxantrone, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Mitoxantrone | ||
|---|---|---|---|
| CAS Number | 65271-80-9 | Molecular Weight | 444.481 |
| Density | 1.5±0.1 g/cm3 | Boiling Point | 805.7±65.0 °C at 760 mmHg |
| Molecular Formula | C22H28N4O6 | Melting Point | 170-174ºC |
| MSDS | / | Flash Point | 441.1±34.3 °C |
Names
| Name | mitoxantrone |
|---|---|
| Synonym | More Synonyms |
Mitoxantrone BiologicalActivity
| Description | Mitoxantrone is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM. |
|---|---|
| Related Catalog | Signaling Pathways >>Epigenetics >>PKCSignaling Pathways >>TGF-beta/Smad >>PKCSignaling Pathways >>Cell Cycle/DNA Damage >>TopoisomeraseResearch 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]. Vibet S, et al. Differential subcellular distribution of mitoxantrone in relation to chemosensitization in two human breast cancer cell lines. Drug Metab Dispos. 2007 May;35(5):822-8. [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. |
Chemical & Physical Properties
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 805.7±65.0 °C at 760 mmHg |
| Melting Point | 170-174ºC |
| Molecular Formula | C22H28N4O6 |
| Molecular Weight | 444.481 |
| Flash Point | 441.1±34.3 °C |
| Exact Mass | 444.200897 |
| PSA | 163.18000 |
| LogP | 0.45 |
| Vapour Pressure | 0.0±3.0 mmHg at 25°C |
| Index of Refraction | 1.709 |
| Storage condition | -20°C Freezer |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 7100 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 :
- 20910 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 :
- 6600 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 :
- Unreported
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 86500 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 :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 16 mg/kg/6W-I
- TOXIC EFFECTS :
- Cardiac - EKG changes not diagnostic of specified effects Liver - other changes Blood - changes in leukocyte (WBC) count
- TYPE OF TEST :
- Specific locus test
- TYPE OF TEST :
- Sex chromosome loss and nondisjunction
- TYPE OF TEST :
- DNA damage
MUTATION DATA - TYPE OF TEST :
- Mutation in mammalian somatic cells
- TEST SYSTEM :
- Rodent - hamster Lung
- DOSE/DURATION :
- 100 ng/L
- REFERENCE :
- PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 26,217,1985
- TYPE OF TEST :
- Mutation in mammalian somatic cells
- TEST SYSTEM :
- Rodent - hamster Lung
- DOSE/DURATION :
- 100 ng/L
- REFERENCE :
- PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 26,217,1985
Safety Information
| Hazard Codes | T,T+ |
|---|---|
| Risk Phrases | R46 |
| Safety Phrases | 53-36/37/39-45-22 |
| RIDADR | 3077.0 |
| WGK Germany | 3 |
| RTECS | CB5748500 |
| Hazard Class | 9.0 |
Synonyms
| 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-anthraquinone |
| mitoxanthrone |
| 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracen-9,10-dion |
| UNII-BZ114NVM5P |
| MFCD00242942 |
| PharmasubstanceEP4 |
| 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyéthyl)amino]éthyl}amino)anthracène-9,10-dione |
| DHAQ |
| 1,4-dihydroxy-5,8-bis[[2-(2-hydroxy-ethylamino)ethyl]amino]anthraquinone |
| 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)- |
| dihydroxyanthraquinone |
| 1,4-dehydroxy-5,8-bis[[[2-(2-hydroxyethyl)amino]ethyl]amino]-9,19-antracenedion |
| 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]- |
| MITOXANTRONUM AND THE INTERMEDIATES |
| 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione |
| 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthraquinone |
| 1,4-bis-[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxy-9,10-anthracenedione |
| 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone |
| Mitoxantrone |
| [3H]-Mitoxantrone |
| MITOXANTRONUM |
