Amifostine trihydrate | CAS#20537-88-6 | CAS#112901-68-5 | radiation-protective agent

MedKoo Cat#: 100050 | Name: Amifostine trihydrate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Amifostine is a phosphorylated aminosulfhydryl compound. After dephosphorylation of amifostine by alkaline phosphatase to an active free sulfhydryl (thiol) metabolite, the thiol metabolite binds to and detoxifies cytotoxic platinum-containing metabolites of cisplatin and scavenges free radicals induced by cisplatin and ionizing radiation. The elevated activity of this agent in normal tissues results from both the relative abundance of alkaline phosphatase in normal tissues and the greater vascularity of normal tissues compared to tumor tissues.

Chemical Structure

Amifostine trihydrate

CAS#112901-68-5 (trihydrate)

Theoretical Analysis

MedKoo Cat#: 100050

Name: Amifostine trihydrate

CAS#: 112901-68-5 (trihydrate)

Chemical Formula: C5H21N2O6PS

Exact Mass: 0.0000

Molecular Weight: 268.26

Elemental Analysis: C, 22.39; H, 7.89; N, 10.44; O, 35.78; P, 11.55; S, 11.95

Price and Availability

Size	Price	Availability
500mg	USD 110.00	Ready to ship
1g	USD 190.00	Ready to ship
2g	USD 325.00	Ready to ship
5g	USD 700.00	Ready to ship
10g	USD 1,250.00	Ready to ship
20g	USD 2,250.00	Ready to ship

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Related CAS #

20537-88-6 (free) 112901-68-5 (trihydrate) 59178-37-9 (sodium) 63717-27-1 (monohydrate)

Synonym

WR2721; WR-2721; WR 2721; YM08310; YM-08310; YM 08310; Aminopropylaminoethylthiophosphoric Acid; ethiofos; gammaphos. US brand name: Ethyol. Abbreviation: APAETP.

IUPAC/Chemical Name

S-(2-((3-aminopropyl)amino)ethyl) O,O-dihydrogen phosphorothioate trihydrate

InChi Key

TXQPXJKRNHJWAX-UHFFFAOYSA-N

InChi Code

InChI=1S/C5H15N2O3PS.3H2O/c6-2-1-3-7-4-5-12-11(8,9)10;;;/h7H,1-6H2,(H2,8,9,10);3*1H2

SMILES Code

OP(O)(SCCNCCCN)=O.[H]O[H].[H]O[H].[H]O[H]

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

Slightly soluble in DMSO, soluble in water (5mg/mL).

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be fromulated in water.

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: 112901-68-5 (Amifostine trihydrate) 20537-88-6 (Amifostine). Accordiong to http://en.wikipedia.org/wiki/Amifostine, amifostine is a cytoprotective adjuvant used in cancer chemotherapy involving DNA-binding chemotherapeutic agents. Also commonly known as WR-1065 in its active form. It is marketed by MedImmune under the trade name Ethyol. Amifostine is used therapeutically to reduce the incidence of neutropenia-related fever and infection induced by DNA-binding chemotherapeutic agents including alkylating agents (e.g. cyclophosphamide) and platinum-containing agents (e.g. cisplatin). It is also used to decrease the cumulative nephrotoxicity associated with platinum-containing agents. Amifostine is also indicated to reduce the incidence of xerostomia in patients undergoing radiotherapy for head and neck cancer. Amifostine was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer. However, while nephroprotection was observed, the fact that amifostine could protect tumors could not be excluded. Given better treatment options for non-small cell lung cancer, this indication for non-small cell lung cancer was withdrawn in 2005. Amifostine is an organic thiophosphate prodrug which is hydrolysed in vivo by alkaline phosphatase to the active cytoprotective thiol metabolite. The selective protection of non-malignant tissues is believed to be due to higher alkaline phosphatase activity, higher pH, and vascular permeation of normal tissues. Amifostine can only be administered intravenously, after reconstitution with normal saline. Infusions lasting less than 15 minutes decrease the risk of adverse effects. The patient should be well-hydrated before administration. Amifostine is a white crystalline powder which is freely soluble in water. Its empirical formula is C5H15N2O3PS and it has a molecular weight of 214.22. ETHYOL is the trihydrate form of amifostine and is supplied as a sterile lyophilized powder requiring reconstitution for intravenous infusion. Each single-use 10 mL vial contains 500 mg of amifostine on the anhydrous basis. Amifostine is a white crystalline powder which is freely soluble in water. Its empirical formula is C5H15N2O3PS and it has a molecular weight of 214.22. ETHYOL is the trihydrate form of amifostine and is supplied as a sterile lyophilized powder requiring reconstitution for intravenous infusion. Each single-use 10 mL vial contains 500 mg of amifostine on the anhydrous basis.

Product Data

Product Data

Certificate of Analysis

View CoA, current batch, lot#BBC41022

QC Data

View QC-data, current batch, lot#BBC41022

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Amifostine trihydrate is a hypoxia-inducible factor-α1 (HIF-α1) and p53 inducer.

In vitro activity:

As depicted in Figure 2(a), there was no difference in the proliferation of cells treated with 0 M, 10−7 M, and 10−9 M AMI (Amifostine). However, the proliferation of cells in the group treated with 10−5 M AMI was significantly inhibited on the seventh day of the experiment. Therefore, AMI was administered at a concentration of 10−7 M in the subsequent experiments. Figure 2(b) demonstrates that the proliferation of BMSCs in group C was significantly inhibited in comparison to that of group A (P < 0.05) on the fifth and seventh days of the experiment. The proliferation of cells on the fifth and seventh days was much higher in the group that received 2 Gy radiation in conjunction with AMI than the group that received 2 Gy radiation alone (P < 0.05). Reference: Stem Cells Int. 2019; 2019: 8749090. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343176/

In vivo activity:

Strikingly, amifostine treatment markedly reduced neurological deficits and appeared to be dose-dependent (Fig. 1A). The percentage of brain infarct area was obviously enlarged in the MCAO/R group, while amifostine treatment apparently diminished it, particularly in the MCAO/R + H group (Fig. 1C). Also, there was a significant increase in brain water content of MCAO/R mice, which could be relieved by amifostine treatment (Fig. 1D). Furthermore, H&E staining displayed the histopathological and morphological alteration of hippocampus CA1 (Fig. 1E). In the sham group, the neuron cell structure was normal, the edge was clear, and the nuclei and intercellular substance were stained evenly. In contrast, the neurons in the MCAO/R group exhibited a disordered arrangement with obvious oedema and necrosis. Importantly, treatment of amifostine significantly attenuated the extent of brain oedema and neuronal necrosis. By using Nissl staining, the results showed that the number of stained Nissl’s bodies was significantly declined in mice of the MCAO/R group. After amifostine treatment, its number was increased significantly (Fig. 1F). These findings provided evidence that amifostine could prevent brain failure caused by I/R. Reference: Folia Neuropathol. 2020;58(4):334-346. https://pubmed.ncbi.nlm.nih.gov/33480238/

Preparing Stock Solutions

The following data is based on the product molecular weight 268.26 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. Huang B, He T, Yao Q, Zhang L, Yao Y, Tang H, Gong P. Amifostine Suppresses the Side Effects of Radiation on BMSCs by Promoting Cell Proliferation and Reducing ROS Production. Stem Cells Int. 2019 Jan 9;2019:8749090. doi: 10.1155/2019/8749090. PMID: 30728842; PMCID: PMC6343176. 2. Wang HT, Yang B, Hu B, Chi XH, Luo LL, Yang HQ, Lang XL, Geng J, Qiao CX, Li Y, Wu XX, Zhu HL, Lv M, Lu XC. The effect of amifostine on differentiation of the human megakaryoblastic Dami cell line. Cancer Med. 2016 Aug;5(8):2012-21. doi: 10.1002/cam4.759. Epub 2016 May 26. PMID: 27228575; PMCID: PMC4884634. 3. Cheng H, Lv M, Mi R, Xue G. Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction. Folia Neuropathol. 2020;58(4):334-346. doi: 10.5114/fn.2020.102436. PMID: 33480238. 4. Pereira AF, Lino JA, Alves BWF, Lisboa MRP, Pontes RB, Leite CAVG, Nogueira RB, Lima-Júnior RCP, Vale ML. Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice. Braz J Med Biol Res. 2020 Sep 18;53(11):e10263. doi: 10.1590/1414-431X202010263. PMID: 32965323; PMCID: PMC7510240.

In vitro protocol:

In vivo protocol:

1. Cheng H, Lv M, Mi R, Xue G. Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction. Folia Neuropathol. 2020;58(4):334-346. doi: 10.5114/fn.2020.102436. PMID: 33480238. 2. Pereira AF, Lino JA, Alves BWF, Lisboa MRP, Pontes RB, Leite CAVG, Nogueira RB, Lima-Júnior RCP, Vale ML. Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice. Braz J Med Biol Res. 2020 Sep 18;53(11):e10263. doi: 10.1590/1414-431X202010263. PMID: 32965323; PMCID: PMC7510240.

1: Rasey JS. Amifostine. Cancer Biother Radiopharm. 1999 Oct;14(5):331-5. doi: 10.1089/cbr.1999.14.331. PMID: 10850317. 2: King M, Joseph S, Albert A, Thomas TV, Nittala MR, Woods WC, Vijayakumar S, Packianathan S. Use of Amifostine for Cytoprotection during Radiation Therapy: A Review. Oncology. 2020;98(2):61-80. doi: 10.1159/000502979. Epub 2019 Dec 17. PMID: 31846959. 3: Bahat Z, Cobanoglu U, Ulku C, Kalyoncu Nİ, Caner Karahan S, Yavuz MN. Could Amifostine Prevent Experimental Radiotherapy-Induced Acute Pericarditis? Asian Pac J Cancer Prev. 2022 Sep 1;23(9):3209-3213. doi: 10.31557/APJCP.2022.23.9.3209. PMID: 36172686; PMCID: PMC9810295. 4: Duval M, Daniel SJ. Meta-analysis of the efficacy of amifostine in the prevention of cisplatin ototoxicity. J Otolaryngol Head Neck Surg. 2012 Oct;41(5):309-15. PMID: 23092832. 5: Nicolatou-Galitis O, Sarri T, Bowen J, Di Palma M, Kouloulias VE, Niscola P, Riesenbeck D, Stokman M, Tissing W, Yeoh E, Elad S, Lalla RV; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of amifostine for the management of oral mucositis in cancer patients. Support Care Cancer. 2013 Jan;21(1):357-64. doi: 10.1007/s00520-012-1613-6. Epub 2012 Oct 3. PMID: 23052919. 6: Singh VK, Seed TM. The efficacy and safety of amifostine for the acute radiation syndrome. Expert Opin Drug Saf. 2019 Nov;18(11):1077-1090. doi: 10.1080/14740338.2019.1666104. Epub 2019 Sep 17. PMID: 31526195. 7: Koukourakis MI. Amifostine: is there evidence of tumor protection? Semin Oncol. 2003 Dec;30(6 Suppl 18):18-30. doi: 10.1053/j.seminoncol.2003.11.014. PMID: 14727237. 8: Shaw LM, Bonner H, Lieberman R. Pharmacokinetic profile of amifostine. Semin Oncol. 1996 Aug;23(4 Suppl 8):18-22. PMID: 8783662. 9: Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007 Jun;12(6):738-47. doi: 10.1634/theoncologist.12-6-738. PMID: 17602063. 10: Yu X, Li M, Zhu L, Li J, Zhang G, Fang R, Wu Z, Jin Y. Amifostine-loaded armored dissolving microneedles for long-term prevention of ionizing radiation- induced injury. Acta Biomater. 2020 Aug;112:87-100. doi: 10.1016/j.actbio.2020.05.025. Epub 2020 May 23. Erratum in: Acta Biomater. 2022 Nov;153:630-631. PMID: 32450231. 11: Foster-Nora JA, Siden R. Amifostine for protection from antineoplastic drug toxicity. Am J Health Syst Pharm. 1997 Apr 1;54(7):787-800. doi: 10.1093/ajhp/54.7.787. PMID: 9099346. 12: Santini V. Amifostine: chemotherapeutic and radiotherapeutic protective effects. Expert Opin Pharmacother. 2001 Mar;2(3):479-89. doi: 10.1517/14656566.2.3.479. PMID: 11336600. 13: van der Vijgh WJ, Korst AE. Amifostine (Ethyol): pharmacokinetic and pharmacodynamic effects in vivo. Eur J Cancer. 1996;32A Suppl 4:S26-30. doi: 10.1016/s0959-8049(96)00332-2. PMID: 8976819. 14: Wasserman TH, Brizel DM. The role of amifostine as a radioprotector. Oncology (Williston Park). 2001 Oct;15(10):1349-54; discussion 1357-60. PMID: 11702962. 15: Koukourakis MI. Amifostine in clinical oncology: current use and future applications. Anticancer Drugs. 2002 Mar;13(3):181-209. doi: 10.1097/00001813-200203000-00001. PMID: 11984063. 16: Gezer A, Karadag-Sari E. The role of amifostine in preventing radiotherapy induced testicular tissue damage in rats. Biotech Histochem. 2022 Apr;97(3):215-221. doi: 10.1080/10520295.2021.1933178. Epub 2021 Jun 1. PMID: 34058938. 17: Koukourakis MI, Maltezos E. Amifostine administration during radiotherapy for cancer patients with genetic, autoimmune, metabolic and other diseases. Anticancer Drugs. 2006 Feb;17(2):133-8. doi: 10.1097/00001813-200602000-00003. PMID: 16428930. 18: Viele C. Amifostine. Clin J Oncol Nurs. 1999 Jul;3(3):128, 131. PMID: 10690046. 19: Mabro M, Faivre S, Raymond E. A risk-benefit assessment of amifostine in cytoprotection. Drug Saf. 1999 Nov;21(5):367-87. doi: 10.2165/00002018-199921050-00003. PMID: 10554052. 20: Capizzi RL. Amifostine reduces the incidence of cumulative nephrotoxicity from cisplatin: laboratory and clinical aspects. Semin Oncol. 1999 Apr;26(2 Suppl 7):72-81. PMID: 10348264.