Mitoxantrone-d₈ dihydrochloride  (Synonyms: Mitozantrone-d₈(dihydrochloride); NSC 301739-d₈ dihydrochloride)

Mitoxantrone-d₈ dihydrochloride is deuterated labeled Mitoxantrone dihydrochloride (HY-13502A). Mitoxantrone dihydrochloride is a potent topoisomerase II inhibitor. Mitoxantrone dihydrochloride also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone dihydrochloride induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone dihydrochloride shows antitumor activity^[1][2][3][4]. Mitoxantrone dihydrochloride also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively^[5].

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Mitoxantrone dihydrochloride inhibits PKC in a competitive manner with respect to histone H1, and its K_i value is 6.3 μM and in a non-competitive manner with respect to phosphatidylserine and ATP^[2].
? Mitoxantrone dihydrochloride (0.5 μg/mL, 48 h) induces a decrease in B-CLL cells. Mitoxantrone dihydrochloride induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of Mitoxantrone dihydrochloride is due to induction of apoptosis^[3].
? Mitoxantrone dihydrochloride shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC₅₀ values of 18 and 196 nM, respectively^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mitoxantrone dihydrochloride (IP, 0-3.2 mg/kg/day) produces a statistically significant number of 60-day survivors at 1.6 mg/kg in mice with IP implanted L1210 leukemia^[5].
? Mitoxantrone dihydrochloride (IV, 0-3.2 mg/kg/day) shows effective antitumor activities and produces a 60% ILS (increase in lifespan) at 3.2 mg/kg in SC implanted Lewis lung carcinoma^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

525.45

C₂₂H₂₂D₈Cl₂N₄O₆

70476-82-3

O=C1C2=C(C(NCCNC([2H])([2H])C([2H])([2H])O)=CC=C2NCCNC([2H])([2H])C([2H])([2H])O)C(C3=C(O)C=CC(O)=C13)=O.[H]Cl.[H]Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. 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.  [Content Brief]

  [3]. Sharon E Altmann, et al. Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone. Antiviral Res. 2012 Feb;93(2):305-308.  [Content Brief]

  [4]. 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.  [Content Brief]

  [5]. 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.  [Content Brief]

  [6]. 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.  [Content Brief]