Synonym
MitoPeroxidase 2; MitoPeroxidase-2; MitoEbselen-2; MitoEbselen 2
IUPAC/Chemical Name
2-[[2-[4-(3-Oxo-1,2-benzoselenazol-2-yl)phenyl]acetyl]amino]ethyl-triphenyl-phosphonium chloride
InChi Key
RWZPPTYDYPSPOY-UHFFFAOYSA-N
InChi Code
InChI=1S/C35H29N2O2PSe.ClH/c38-34(26-27-20-22-28(23-21-27)37-35(39)32-18-10-11-19-33(32)41-37)36-24-25-40(29-12-4-1-5-13-29,30-14-6-2-7-15-30)31-16-8-3-9-17-31;/h1-23H,24-26H2;1H
SMILES Code
O=C(NCC[P+](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)CC4=CC=C(N5[Se]C6=CC=CC=C6C5=O)C=C4.[Cl-]
Purity
>97% (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
Shelf Life
>3 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
Ionizing radiation (IR) triggers mitochondrial overproduction of H2O2 and accumulation of lipid hydroperoxides leading to the induction of apoptotic and necroptotic cell death pathways. Exposure of eukaryotic cells to ionizing radiation (IR) results in a burst of species with high energy (eaq−; H•, HO•, and O2−•) and indiscriminate reactivity with biomolecules, including DNA, on the millisecond time scale.1 Studies by Patt, Bacq, and others have established that aminothiols such as cysteine and cysteamine protect mice from short-lived radiolytic intermediates.2−4 Humans, however, do not tolerate the doses of cysteine and cysteamine, which would be required for analogous protection, and the early hope that these compounds might be useful as radiation protectors (RPs) has
not been realized.
Biological target:
MitoEbselen-2, also known as MitoPeroxidase-2, is a radiation mitigator which reduces lipid hydroperoxides.
In vitro activity:
Exposure of MEC to γ-irradiation (10 Gy) resulted in ∼28% cell death (Figure 2B), whereas treatment with MitoEbselen-2 (MitoPeroxidase 2), prior to or 30 min postirradiation, afforded radioprotection/mitigation. 20 μM MitoPeroxidase 2 afforded ∼50% radioprotection/mitigation. In this model system, MitoEbselen-2 (MitoPeroxidase 2) acted as a potent inhibitor of radiation-induced activation of caspase 3 (Figure 3), an executioner caspase in apoptosis. Treatment of irradiated MEC with 3-hydroxypropyl(triphenyl)phosphonium chloride, which structurally mimics the triphenylphosphonium moieties of MitoPeroxidases 1 and 2, did not afford any radiomitigation (data not shown).
Reference: ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25530831/
In vivo activity:
Groups of 15 mice were treated with MitoPeroxidase 2 i.v. at 24 h after WBI. As shown in Figure 4, at two different radiation doses, administration of MitoPeroxidase 2 afforded an increase in survival.
Reference: ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25530831/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Soluble in DMSO |
0.0 |
0.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
656.02
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 |
In vitro protocol:
1. Stoyanovsky DA, Jiang J, Murphy MP, Epperly M, Zhang X, Li S, Greenberger J, Kagan V, Bayır H. Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator. ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. doi: 10.1021/ml5003635. PMID: 25530831; PMCID: PMC4266336.
In vivo protocol:
1. Stoyanovsky DA, Jiang J, Murphy MP, Epperly M, Zhang X, Li S, Greenberger J, Kagan V, Bayır H. Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator. ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. doi: 10.1021/ml5003635. PMID: 25530831; PMCID: PMC4266336.
1: Stoyanovsky DA, Jiang J, Murphy MP, Epperly M, Zhang X, Li S, Greenberger J, Kagan V, Bayır H. Correction to "Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator". ACS Med Chem Lett. 2016 Jun 1;7(6):653-4. doi: 10.1021/acsmedchemlett.6b00212. eCollection 2016 Jun 9. PubMed PMID: 27326344; PubMed Central PMCID: PMC4910416.
2: Stoyanovsky DA, Jiang J, Murphy MP, Epperly M, Zhang X, Li S, Greenberger J, Kagan V, Bayır H. Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator. ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. eCollection 2014 Dec 11. PubMed PMID: 25530831; PubMed Central PMCID: PMC4266336.
