WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100057
CAS#: 54301-15-4 (HCl)
Description: Amsacrine is an aminoacridine derivative with potential antineoplastic activity. Although its mechanism of action is incompletely defined, amsacrine may intercalate into DNA and inhibit topoisomerase II, resulting in DNA double-strand breaks, arrest of the S/G2 phase of the cell cycle, and cell death. This agent's cytotoxicity is maximal during the S phase of the cell cycle when topoisomerase levels are greatest. In addition, amsacrine may induce transcription of tumor promoter p53 protein and block p53 ubiquitination and proteasomal degradation, resulting in p53-dependent tumor cell apoptosis.
Hodoodo Cat#: H100057
Name: Amsacrine HCl
CAS#: 54301-15-4 (HCl)
Chemical Formula: C21H20ClN3O3S
Exact Mass: 0.00
Molecular Weight: 429.920
Elemental Analysis: C, 58.67; H, 4.69; Cl, 8.25; N, 9.77; O, 11.16; S, 7.46
Related CAS #: 54301-16-5 (mesylate) 80277-11-8 (lactate) 54301-15-4 (HCl) 80277-07-2 (gluconate) 51264-14-3 (free base)
Synonym: acridinyl anisidide; Cains Acridine. US brand name: Amsa PD. Foreign brand names: Amekrin; Amsidine; Amsidyl; Lamasine. Abbreviations: AMSA; mAMSA. Code names: CI880; SN11841.
IUPAC/Chemical Name: N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide hydrochloride
InChi Key: WDISRLXRMMTXEV-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H19N3O3S.ClH/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21;/h3-13,24H,1-2H3,(H,22,23);1H
SMILES Code: CS(=O)(NC1=CC=C(NC2=C(C=CC=C3)C3=NC4=CC=CC=C42)C(OC)=C1)=O.[H]Cl
Appearance: white 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
More Info: Related: 51264-14-3 (Amsacrine) 54301-15-4 (Amsacrine HCl).
| Biological target: | Amsacrine hydrochloride (m-AMSA hydrochloride; acridinyl anisidide hydrochloride) is an inhibitor of topoisomerase II. |
| In vitro activity: | As shown in Figure 1B, cell treatment with m-AMSA dose ranging from 5 to 50 nM showed an approximately 6–12% decrease in U937, Jurkat, HL-60, KU812, and MEG-01 cell viability, while there was no significant loss in the viability of K562 cells after m-AMSA treatment. These results reflected that m-AMSA exerted marginal cytotoxicity on leukemia cells. Figure 1C shows that m-AMSA notably inhibited leukemia cell invasion. Western blot analysis showed that m-AMSA treatment reduced MMP-2 and MMP-9 protein expression (Fig. 1E). Figure 1F reveals that MMP-2 mRNA and MMP-9 mRNA levels in m-AMSA-treated cells were lower than those in untreated control cells as evidenced by real-time PCR assay. mRNA stability analysis following transcription inhibition by actinomycin D showed that m-AMSA notably reduced MMP-2/MMP-9 mRNA stability in U937, K562, and Jurkat cells as evidenced by real-time PCR analyses (Fig. 1H). These results indicated that m-AMSA-induced MMP-2/MMP-9 down-regulation inhibited leukemia cell invasion, and suggested that the m-AMSA suppressive effect on MMP-2/MMP-9 expression was associated with reduced MMP-2/MMP-9 transcription and mRNA stability. Reference: J Cell Physiol. 2014 May;229(5):588-98. https://onlinelibrary-wiley-com.libproxy.lib.unc.edu/doi/10.1002/ |
| In vivo activity: | These results show that postoperative IOP (intraocular pressure) in rabbit eyes treated with 10% AMSA (amsacrine) was lower than in eyes treated with saline on day 7 after surgery. This suggests that AMSA is effective and begins to act during an early phase of wound healing. Furthermore, the difference in postoperative IOP between the 0.04% MMC and 10% AMSA groups started to widen after 21 days. This suggests that AMSA might also have an additional mechanism of action during the remodeling phase, which in rabbits corresponds to the period later than day 21 after surgery. Reference: Sci Rep. 2019; 9: 19288. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917768/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 37.3 | 86.64 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.16 | |
| DMF | 10.0 | 23.26 |
The following data is based on the product molecular weight 429.92 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.
| 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. Liu WH, Chen YJ, Chien JH, Chang LS. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells. J Cell Physiol. 2014 May;229(5):588-98. doi: 10.1002/jcp.24481. PMID: 24122234. 2. Yamamoto K, Kokubun T, Sato K, Akaishi T, Shimazaki A, Nakamura M, Shiga Y, Tsuda S, Omodaka K, Saya H, Nakazawa T. The DNA topoisomerase II inhibitor amsacrine as a novel candidate adjuvant in a model of glaucoma filtration surgery. Sci Rep. 2019 Dec 17;9(1):19288. doi: 10.1038/s41598-019-55365-7. PMID: 31848363; PMCID: PMC6917768. 3. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33. doi: 10.1002/jat.1753. Epub 2011 Nov 11. PMID: 22081495. |
| In vitro protocol: | 1. Liu WH, Chen YJ, Chien JH, Chang LS. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells. J Cell Physiol. 2014 May;229(5):588-98. doi: 10.1002/jcp.24481. PMID: 24122234. |
| In vivo protocol: | 1. Yamamoto K, Kokubun T, Sato K, Akaishi T, Shimazaki A, Nakamura M, Shiga Y, Tsuda S, Omodaka K, Saya H, Nakazawa T. The DNA topoisomerase II inhibitor amsacrine as a novel candidate adjuvant in a model of glaucoma filtration surgery. Sci Rep. 2019 Dec 17;9(1):19288. doi: 10.1038/s41598-019-55365-7. PMID: 31848363; PMCID: PMC6917768. 2. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33. doi: 10.1002/jat.1753. Epub 2011 Nov 11. PMID: 22081495. |
1: Jangir DK, Kundu S, Mehrotra R. Role of minor groove width and hydration pattern on amsacrine interaction with DNA. PLoS One. 2013 Jul 29;8(7):e69933. doi: 10.1371/journal.pone.0069933. Print 2013. PubMed PMID: 23922861; PubMed Central PMCID: PMC3726726.
2: Krejci M, Doubek M, Dusek J, Brychtova Y, Racil Z, Navratil M, Tomiska M, Horky O, Pospisilova S, Mayer J. Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia. Ann Hematol. 2013 Jun 1. [Epub ahead of print] PubMed PMID: 23728608.
3: Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. doi: 10.1200/JCO.2012.46.4743. Epub 2013 Apr 29. PubMed PMID: 23630210.
4: Fong CY, Grigoriadis G, Hocking J, Coutsouvelis J, Muirhead J, Campbell P, Paul E, Walker P, Avery S, Patil S, Spencer A, Schwarer A, Wei A. Fludarabine, cytarabine, granulocyte-colony stimulating factor and amsacrine: an effective salvage therapy option for acute myeloid leukemia at first relapse. Leuk Lymphoma. 2013 Feb;54(2):336-41. doi: 10.3109/10428194.2012.713479. Epub 2012 Sep 8. PubMed PMID: 22812445.
5: Jangir DK, Dey SK, Kundu S, Mehrotra R. Assessment of amsacrine binding with DNA using UV-visible, circular dichroism and Raman spectroscopic techniques. J Photochem Photobiol B. 2012 Sep 3;114:38-43. doi: 10.1016/j.jphotobiol.2012.05.005. Epub 2012 May 18. PubMed PMID: 22677564.
6: Ketron AC, Denny WA, Graves DE, Osheroff N. Amsacrine as a topoisomerase II poison: importance of drug-DNA interactions. Biochemistry. 2012 Feb 28;51(8):1730-9. doi: 10.1021/bi201159b. Epub 2012 Feb 10. PubMed PMID: 22304499; PubMed Central PMCID: PMC3289736.
7: Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33. doi: 10.1002/jat.1753. Epub 2011 Nov 11. PubMed PMID: 22081495.
8: Devi ML, Chandrasekhar KB, Surendranath KV, Rao BM, Narayana MB. A validated stability-indicating RP-HPLC assay method for Amsacrine and its related substances. J Chromatogr Sci. 2011 Aug;49(7):489-94. PubMed PMID: 21801478.
9: Wilhelm C, Neubauer A, Burchert A. Poor-risk cytogenetics may be associated with inferior outcome after fludarabine, cytarabine, and amsacrine reduced intensity conditioning in patients with high-risk acute myeloid leukemia. Leuk Lymphoma. 2011 Oct;52(10):2031-5. doi: 10.3109/10428194.2011.588760. Epub 2011 Jun 24. PubMed PMID: 21702642.
10: Zhang L, Guo Y, Wang J, Wang X, Han G, Ou W, Xu Y, Zhang X. Assisted sonodynamic damage of bovine serum albumin by metronidazole under ultrasonic irradiation combined with photosensitive antitumor drug-Amsacrine. J Photochem Photobiol B. 2010 Jan 21;98(1):61-8. doi: 10.1016/j.jphotobiol.2009.11.005. Epub 2009 Nov 22. PubMed PMID: 20006932.
