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Purity: ≥98%
Amifostine trihydrate (WR2721), a phosphorylated aminosulfhydryl compound, is the first approved radioprotective drug, it is used to decrease the risk of kidney problems caused by treatment with cisplatin. 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.
Targets |
hypoxia-inducible factor-α1 (HIF-α1); p53
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ln Vitro |
Amifostine (0.78125-100 μM, 24 h) trihydrate dramatically lowers H9c2 cell apoptosis at a concentration of 100 μM and decreases tert-butyl hydroperoxide (TBHP)-induced cell damage in a dose-dependent manner [5].
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ln Vivo |
Male C57BL/6 mice that have myocardial I/R injury are protected against it by amifostine (intravenous injection, 400 mg/kg, 4 h) trihydrate [5].
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Enzyme Assay |
We used TBHP, a more stable chemical than H2O2, to induce oxidative stress. For measurement of ROS of the H9c2 cells, cells were incubated with 10 μmol/L ROS sensitive dye 2′,7′-dichloruoresceindiacetate (DCFH-DA) at 37°C for 20 min. ROS was detected by a flow cytometry sorter (BD Biosciences, San Jose, CA, USA) and quantified by BD FACS software. The above experiments were repeated three times. ΔΨm was measured using JC-1 staining; cells were seeded into Petri dishes. After treatment, the dishes were incubated in JC-1 staining solution (5 mg/ml) at 37°C for 20 min. Subsequently the staining cells were washed twice with JC-1 staining buffer; images were taken by a confocal laser scanning microscopy.[5]
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Cell Assay |
H9c2 cells were seeded into 96-well plates at a concentration of 5000 cells per well. The cells were pretreated with amifostine (0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 μM) for 30 min before being exposure to tert-Butyl hydroperoxide (TBHP) for 12 h. The number of viable cells was evaluated by MTT assay. Briefly, MTT dye solution was added to each well and incubated for 4 h. The number of viable cells was measured by evaluating Absorbance at 490 nm. The MTT assay was repeated three times for consistency.[5]
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Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice with myocardial I/R injury [5]
Doses: 400 mg/kg Route of Administration: intravenous (iv) injection; 4 hrs (hours)) Experimental Results: Attenuated cardiomyocyte apoptosis and diminished I/R-induced ROS production. Dramatically diminished the expression of cleaved caspase 3 and Bax, while enhancing the expression of SOD1, SOD2 and Bcl2. SOD activity was Dramatically increased and MDA levels were diminished. |
References |
[1]. D Maurici, et al. Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay. Oncogene. 2001 Jun 14;20(27):3533-40.
[2]. Efstathia Giannopoulou, et al. Amifostine inhibits angiogenesis in vivo. J Pharmacol Exp Ther. 2003 Feb;304(2):729-37. [3]. Michael I Koukourakis, et al. Amifostine induces anaerobic metabolism and hypoxia-inducible factor 1 alpha. Cancer Chemother Pharmacol. 2004 Jan;53(1):8-14. [4]. John R Kouvaris, et al. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007 Jun;12(6):738-47. [5]. Shao-Ze Wu, et al. Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress. Oxid Med Cell Longev. 2017;2017:4130824. |
Molecular Formula |
C5H15N2O3PS.3H2O
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Molecular Weight |
268.27
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Exact Mass |
268.085794
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Elemental Analysis |
C, 22.39; H, 7.89; N, 10.44; O, 35.78; P, 11.55; S, 11.95
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CAS # |
112901-68-5
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Related CAS # |
20537-88-6 (free); 112901-68-5 (trihydrate); 59178-37-9 (sodium); 63717-27-1 (monohydrate)
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Appearance |
White to off-white solid powder
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tPSA |
124Ų
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SMILES |
S(C([H])([H])C([H])([H])N([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])P(=O)(O[H])O[H].O([H])[H].O([H])[H].O([H])[H]
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InChi Key |
TXQPXJKRNHJWAX-UHFFFAOYSA-N
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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
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Chemical Name |
S-(2-((3-aminopropyl)amino)ethyl) O,O-dihydrogen phosphorothioate trihydrate
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.7276 mL | 18.6379 mL | 37.2759 mL | |
5 mM | 0.7455 mL | 3.7276 mL | 7.4552 mL | |
10 mM | 0.3728 mL | 1.8638 mL | 3.7276 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00003624 | Terminated | Drug: amifostine trihydrate Drug: cisplatin Drug: paclitaxel |
Cervical Cancer Endometrial Cancer |
Gynecologic Oncology Group | December 1998 | Phase 2 |
NCT00503776 | Terminated | Drug:amifostine trihydrate Procedure:therapeutic dietary intervention |
Dysphagia Head and Neck Cancer |
Vanderbilt-Ingram Cancer Center |
January 2006 | Phase 2 |
NCT00003048 | Completed | Drug:Amifostine Trihydrate | Myelodysplastic Syndromes | M.D. Anderson Cancer Center |
June 5, 1997 | Phase 2 |
NCT00098683 | Completed | Drug:amifostine trihydrate | Myelodysplastic Syndromes | Children's Oncology Group | January 2005 | Phase 2 |
NCT00003123 | Unknown | Drug: amifostine trihydrate | Myelodysplastic Syndromes | Providence Hospital | August 1997 | Phase 2 |
Effect of amifostine pretreatment on TBHP-induced apoptosis in H9c2 cells. (a) Typical images of flow cytometry. (b) The apoptosis ratio was quantified by BD FACS software. Amifostine pretreatment (TBHP + H group) significantly reduced apoptosis compared with the TBHP group. Data are shown as means ± SEM; ∗P < 0.05, TBHP group versus control group, #P < 0.05, TBHP + H group versus TBHP group; n = 6 per group. [5].Oxid Med Cell Longev. 2017;2017:4130824. td> |
The effect of amifostine pretreatment on mitochondrial membranes potential changes (ΔΨm) in H9c2 cells cultured with TBHP. The ΔΨm of TBHP group remarkably decreased compared with control group; the ΔΨm in TBHP + H group was increased compared to the TBHP group. n = 6 per group. [5].Oxid Med Cell Longev. 2017;2017:4130824. td> |
The effect of amifostine pretreatment on myocardial TUNEL staining. (a) Representative confocal microscopy images. White triangle indicates positive staining cells (green). DAPI staining (blue) indicates nucleus. Magnification: ×400. (b) Percentages of TUNEL positive cells of total cells. Data are shown as means ± SEM; ∗P < 0.05, I/R group versus Sham group, #P < 0.05, I/R + H group versus I/R group; n = 6 per group. [5].Oxid Med Cell Longev. 2017;2017:4130824. td> |