Mitoxantrone HCl
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MedKoo CAT#: 100650

CAS#: 70476-82-3 (HCl)

Description: Mitoxantrone is an anthraquinone that intercalates in DNA and inhibits topoisomerase II (IC50 = 5.3 μM), thus inhibiting cell proliferation. It also inhibits HIV-1 integrase (IC50 = 3.8 μM). Mitoxantrone is exported from cells in an ATP- and glutathione-dependent manner by multidrug resistance protein-1.4 Formulations containing mitoxantrone have been used in the treatment of cancer and multiple sclerosis.


Chemical Structure

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Mitoxantrone HCl
CAS# 70476-82-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 100650
Name: Mitoxantrone HCl
CAS#: 70476-82-3 (HCl)
Chemical Formula: C22H30Cl2N4O6
Exact Mass:
Molecular Weight: 517.4
Elemental Analysis: C, 51.07; H, 5.84; Cl, 13.70; N, 10.83; O, 18.55

Price and Availability

Size Price Availability Quantity
50.0mg USD 90.0 Ready to ship
100.0mg USD 150.0 Ready to ship
200.0mg USD 250.0 Ready to ship
500.0mg USD 550.0 Ready to ship
1.0g USD 950.0 Ready to ship
2.0g USD 1650.0 Ready to ship
5.0g USD 3650.0 Ready to ship
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Related CAS #: 70476-82-3 (HCl)   65271-80-9 (free base)    

Synonym: DHAQ; CL-232325; CL 232325; CL232325; Mitozantrone; Mitoxantrone HCl; Mitoxantrone dihydrchloride; US brand name: Novantrone. Foreign brand names: Mitroxone; Neotalem; Onkotrone; Pralifan.

IUPAC/Chemical Name: 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)anthracene-9,10-dione dihydrochloride

InChi Key: ZAHQPTJLOCWVPG-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H28N4O6.2ClH/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32;;/h1-4,23-30H,5-12H2;2*1H

SMILES Code: O=C1C2=C(C(NCCNCCO)=CC=C2NCCNCCO)C(C3=C(O)C=CC(O)=C13)=O.[H]Cl.[H]Cl

Appearance: Black solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM.
In vitro activity: Given that MD (mitoxantrone dihydrochloride) inhibited viral toxicity and suppressed the expression levels of viral proteins, it was further confirmed whether the transcription levels of viral genes were also affected by MD. To examine the effects of MD on HSV-1 gene expression, total RNA was extracted from the treated cells, and Q-PCR was performed using specific primers as described in the Methods. The transcription levels of the ICP6 and GB genes were reduced by MD (Fig. 4a). This result was consistent with the observation of the protein levels by western blot (Fig.2). HSV-1 genes such as UL5, UL8, UL9, UL42 and UL52 are required for viral DNA replication. It was found that the transcription levels of these genes were also inhibited by MD (Fig.4b). Remarkably, MD also reduced the transcription levels of the immediate early genes ICP0, ICP22, ICP27, and ICP47, all of which are required for the expression of early and late viral gene products (Fig.4c). These results suggest that MD inhibits HSV-1 replication by suppressing the expression of immediate early genes. Having shown that MD suppressed the transcription of immediate early genes, it was sought to characterize whether MD affects the promoter activity of immediate early genes. A pGL4.17-based luciferase construct was generated containing the ICP0 promoter sequence. Using a luciferase reporter assay, it was found that MD had no effect on the promoter activity of ICP0, which suggests that MD interfered with the transcription of viral immediate early genes without affecting the promoter activity of ICP0 (Fig.44d). Reference: BMC Microbiol. 2019; 19: 274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898960/
In vivo activity: To determine whether MXN (mitoxantrone) was effective against CPXV (cowpox virus) in vivo, 0.25 mg/kg or 0.5 mg/kg of drug was administered intraperitoneally to 4– 6 week old female C57Bl/6 mice one day post- intraperitoneal inoculation. Log-rank tests were performed comparing survival times between the two MXN treatment groups relative the mock-treated group. A p-value of 0.025 was considered statistically significant, after a Bonferroni correction for the comparisons of the two MXN dose groups to the mock-treated The lower dose of MXN significantly improved the survival time of infected animals, with the median day-of-death (MDD) in infected animals increasing from day 7 to day 9 (p=0.0015). The 0.5 mg/kg dose of MXN improved the MDD to 12 days (p= 0.0005). Twenty-five percent of the animals treated with 0.5 mg/kg MXN survived compared to 5% of mock-treated animals (Figure 2). Reference: Antiviral Res. 2012 Feb; 93(2): 305–308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272698/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 55.0 106.3
H2O 64.0 123.7
DMSO 55.0 106.3
H2O 64.0 123.7

Preparing Stock Solutions

The following data is based on the product molecular weight 517.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Huang Q, Hou J, Yang P, Yan J, Yu X, Zhuo Y, He S, Xu F. Antiviral activity of mitoxantrone dihydrochloride against human herpes simplex virus mediated by suppression of the viral immediate early genes. BMC Microbiol. 2019 Dec 7;19(1):274. doi: 10.1186/s12866-019-1639-8. PMID: 31812160; PMCID: PMC6898960. 2. Bellosillo B, Colomer D, Pons G, Gil J. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. doi: 10.1046/j.1365-2141.1998.00520.x. PMID: 9450803. 3. Fujimoto S, Ogawa M. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. doi: 10.1007/BF00255476. PMID: 7105379. 4. Altmann SE, Smith AL, Dyall J, Johnson RF, Dodd LE, Jahrling PB, Paragas J, Blaney JE. Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone. Antiviral Res. 2012 Feb;93(2):305-308. doi: 10.1016/j.antiviral.2011.12.001. Epub 2011 Dec 11. PMID: 22182595; PMCID: PMC3272698.
In vitro protocol: 1. Huang Q, Hou J, Yang P, Yan J, Yu X, Zhuo Y, He S, Xu F. Antiviral activity of mitoxantrone dihydrochloride against human herpes simplex virus mediated by suppression of the viral immediate early genes. BMC Microbiol. 2019 Dec 7;19(1):274. doi: 10.1186/s12866-019-1639-8. PMID: 31812160; PMCID: PMC6898960. 2. Bellosillo B, Colomer D, Pons G, Gil J. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. doi: 10.1046/j.1365-2141.1998.00520.x. PMID: 9450803.
In vivo protocol: 1. Fujimoto S, Ogawa M. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. doi: 10.1007/BF00255476. PMID: 7105379. 2. Altmann SE, Smith AL, Dyall J, Johnson RF, Dodd LE, Jahrling PB, Paragas J, Blaney JE. Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone. Antiviral Res. 2012 Feb;93(2):305-308. doi: 10.1016/j.antiviral.2011.12.001. Epub 2011 Dec 11. PMID: 22182595; PMCID: PMC3272698.

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1. Yang Y, Wu ZX, Wang JQ, Teng QX, Lei ZN, Lusvarghi S, Ambudkar SV, Chen ZS, Yang DH. OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance. Front Pharmacol. 2021 Feb 15;12:620874. doi: 10.3389/fphar.2021.620874. PMID: 33658942; PMCID: PMC7917255.

1: Kapoor T, Mehan S. Neuroprotective methodologies in treatment of Multiple Sclerosis: Current status of Clinical and Pre-clinical findings. Curr Drug Discov Technol. 2020 Feb 6. doi: 10.2174/1570163817666200207100903. [Epub ahead of print] PubMed PMID: 32031075.

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3: Zinzani PL, Derenzini E, Pellegrini C, Rigacci L, Fabbri A, Gandolfi L, Argnani L, Casadei B, Pulsoni A, Gobbi M, Perotti A, Zaccaria A, Voso MT, Cabras MG, De Renzo A. Long-term efficacy and toxicity results of the FLUMIZ trial (fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in untreated follicular lymphoma). Ann Oncol. 2012 Mar;23(3):805-807. doi: 10.1093/annonc/mdr633. Epub 2019 Dec 4. PubMed PMID: 32018684.

4: Scheckel CJ, Meyer M, Betcher JA, Al-Kali A, Foran J, Palmer J. Efficacy of mitoxantrone-based salvage therapies in relapsed or refractory acute myeloid leukemia in the Mayo Clinic Cancer Center: Analysis of survival after 'CLAG-M' vs. 'MEC'. Leuk Res. 2020 Jan 28;90:106300. doi: 10.1016/j.leukres.2020.106300. [Epub ahead of print] PubMed PMID: 32018118.

5: Djeni TN, Kouame KH, Ake FDM, Amoikon LST, Dje MK, Jeyaram K. Microbial Diversity and Metabolite Profiles of Palm Wine Produced From Three Different Palm Tree Species in Côte d'Ivoire. Sci Rep. 2020 Feb 3;10(1):1715. doi: 10.1038/s41598-020-58587-2. PubMed PMID: 32015447.

6: Lin KN, Jiang YL, Zhang SG, Huang SY, Li H. Grape seed proanthocyanidin extract reverses multidrug resistance in HL-60/ADR cells via inhibition of the PI3K/Akt signaling pathway. Biomed Pharmacother. 2020 Jan 30;125:109885. doi: 10.1016/j.biopha.2020.109885. [Epub ahead of print] PubMed PMID: 32007917.

7: Baltes F, Pfeifer V, Silbermann K, Caspers J, Wantoch von Rekowski K, Schlesinger M, Bendas G. β(1)-Integrin binding to collagen type 1 transmits breast cancer cells into chemoresistance by activating ABC efflux transporters. Biochim Biophys Acta Mol Cell Res. 2020 Jan 25;1867(5):118663. doi: 10.1016/j.bbamcr.2020.118663. [Epub ahead of print] PubMed PMID: 31987794.

8: Liu Y, Liao Y, Li P, Li ZT, Ma D. Cross-Linked Pillar[6]arene Nanosponges Fabricated by the Use of a Supra-Amphiphilic Template: Cargo Encapsulation and Overcoming Multidrug Resistance. ACS Appl Mater Interfaces. 2020 Feb 5. doi: 10.1021/acsami.9b22066. [Epub ahead of print] PubMed PMID: 31985197.

9: Burke MJ, Kostadinov R, Sposto R, Gore L, Kelley SM, Rabik C, Trepel JB, Lee MJ, Yuno A, Lee S, Bhojwani D, Jeha S, Chang BH, Sulis ML, Hermiston ML, Gaynon P, Huynh V, Verma A, Gardner R, Heym KM, Dennis RM, Ziegler DS, Laetsch TW, Oesterheld JE, Dubois SG, Pollard JA, Glade-Bender J, Cooper TM, Kaplan JA, Farooqi MS, Yoo B, Guest E, Wayne AS, Brown PA. Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study. Clin Cancer Res. 2020 Jan 22. pii: clincanres.1251.2019. doi: 10.1158/1078-0432.CCR-19-1251. [Epub ahead of print] PubMed PMID: 31969338.

10: Wu ZX, Yang Y, Teng QX, Wang JQ, Lei ZN, Wang JQ, Lusvarghi S, Ambudkar SV, Yang DH, Chen ZS. Tivantinib, A c-Met Inhibitor in Clinical Trials, Is Susceptible to ABCG2-Mediated Drug Resistance. Cancers (Basel). 2020 Jan 12;12(1). pii: E186. doi: 10.3390/cancers12010186. PubMed PMID: 31940916.

11: Wawrzyniak S, Rzepiński Ł. Is there a new place for mitoxantrone in the treatment of multiple sclerosis? Neurol Neurochir Pol. 2020 Jan 10. doi: 10.5603/PJNNS.a2019.0069. [Epub ahead of print] PubMed PMID: 31922582.

12: Najafian J, Nasri A, Etemadifar M, Salehzadeh F. Late Cardiotoxicity in MS Patients Treated with Mitoxantrone. Int J Prev Med. 2019 Dec 10;10:211. doi: 10.4103/ijpvm.IJPVM_477_17. eCollection 2019. PubMed PMID: 31921403; PubMed Central PMCID: PMC6941302.

13: Thiele Née Schrewe L, Guse K, Tietz S, Remlinger J, Demir S, Pedreiturria X, Hoepner R, Salmen A, Pistor M, Turner T, Engelhardt B, Hermann DM, Lühder F, Wiese S, Chan A. Functional relevance of the multi-drug transporter abcg2 on teriflunomide therapy in an animal model of multiple sclerosis. J Neuroinflammation. 2020 Jan 8;17(1):9. doi: 10.1186/s12974-019-1677-z. PubMed PMID: 31915017; PubMed Central PMCID: PMC6951012.

14: Chang A. A case of mitoxantrone extravasation. J Oncol Pharm Pract. 2020 Jan 6:1078155219893736. doi: 10.1177/1078155219893736. [Epub ahead of print] PubMed PMID: 31902285.

15: Wu J, Lin Z, Weng X, Owens G, Chen Z. Removal mechanism of mitoxantrone by a green synthesized hybrid reduced graphene oxide @ iron nanoparticles. Chemosphere. 2019 Dec 19;246:125700. doi: 10.1016/j.chemosphere.2019.125700. [Epub ahead of print] PubMed PMID: 31884233.

16: Cornet C, Dyballa S, Terriente J, Di Giacomo V. ZeOncoTest: Refining and Automating the Zebrafish Xenograft Model for Drug Discovery in Cancer. Pharmaceuticals (Basel). 2019 Dec 24;13(1). pii: E1. doi: 10.3390/ph13010001. PubMed PMID: 31878274.

17: Pumuye PP, Evison BJ, Konda SK, Collins JG, Kelso C, Medan J, Sleebs BE, Watson K, Phillips DR, Cutts SM. Formaldehyde-activated WEHI-150 induces DNA interstrand crosslinks with unique structural features. Bioorg Med Chem. 2020 Feb 1;28(3):115260. doi: 10.1016/j.bmc.2019.115260. Epub 2019 Dec 14. PubMed PMID: 31870833.

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19: Rossi A, Pakhomova ON, Mollica PA, Casciola M, Mangalanathan U, Pakhomov AG, Muratori C. Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied by Immunogenic Cell Death in Murine Models of Lymphoma and Colorectal Cancer. Cancers (Basel). 2019 Dec 17;11(12). pii: E2034. doi: 10.3390/cancers11122034. PubMed PMID: 31861079; PubMed Central PMCID: PMC6966635.

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Additional Information

 
NOVANTRONE® (mitoxantrone hydrochloride) is a synthetic antineoplastic anthracenedione for intravenous use. The molecular formula is C22H28N4O6•2HCl and the molecular weight is 517.41. It is supplied as a concentrate that MUST BE DILUTED PRIOR TO INJECTION. The concentrate is a sterile, nonpyrogenic, dark blue aqueous solution containing mitoxantrone hydrochloride equivalent to 2 mg/mL mitoxantrone free base, with sodium chloride (0.80% w/v), sodium acetate (0.005% w/v), and acetic acid (0.046% w/v) as inactive ingredients. The solution has a pH of 3.0 to 4.5 and contains 0.14 mEq of sodium per mL. The product does not contain preservatives.
 
 
Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. NOVANTRONE® has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen pre sentation, as well as the secretion of interferon gamma, TNFα, and IL-2.
Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. NOVANTRONE® has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen pre sentation, as well as the secretion of interferon gamma, TNFα, and IL-2.
Mitoxantrone is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination has been the first line of treatment, until recently, when combination of docetaxel and prednisone has been shown to improve survival and disease-free period. Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset known as secondary progressive MS. Mitoxantrone will not cure multiple sclerosis, but is effective in slowing the progression of secondary progressive MS and extending the time between relapses in relapsing-remitting MS and progressive relapsing MS.
Mitoxantrone
is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination has been the first line of treatment, until recently, when combination of docetaxel and prednisone has been shown to improve survival and disease-free period. Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset known as secondary progressive MS. Mitoxantrone will not cure multiple sclerosis, but is effective in slowing the progression of secondary progressive MS and extending the time between relapses in relapsing-remitting MS and progressive relapsing MS.