Methylproamine
目录号 : GC36601
Methylproamine是DNA结合的辐射保护剂，能修复辐射诱导的短暂活性氧。
Cas No.:188247-01-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA.IC50 Value: N/ATarget: DNA-binding radioprotectorin vitro: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM [1]. Methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence ofmethylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay [2]. Experiments with V79 cells have shown that methylproamine is approximately 100-fold more potent than the classical aminothiol radioprotector WR1065. The crystal structures of methylproamine and proamine complexes with the dodecamer d(CGCGAATTCGCG)(2) confirm that the new analogues also are minor groove binders [3].in vivo: N/AClinical trial: N/A
[1]. Lobachevsky PN, Vasireddy RS, Broadhurst S, Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage. Int J Radiat Biol. 2011 Mar;87(3):274-83. [2]. Sprung CN, Vasireddy RS, Karagiannis TC, Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks. Mutat Res. 2010 Oct 13;692(1-2):49-52. [3]. Martin RF, Broadhurst S, Reum ME, In vitro studies with methylproamine: a potent new radioprotector. Cancer Res. 2004 Feb 1;64(3):1067-70.
| Cas No. | 188247-01-0 | SDF | |
| Canonical SMILES | CN1CCN(C2=CC=C3C(N=C(C4=CC=C5C(N=C(C6=CC=C(N(C)C)C=C6C)N5)=C4)N3)=C2)CC1 | ||
| 分子式 | C28H31N7 | 分子量 | 465.59 |
| 溶解度 | DMSO: ≥ 41 mg/mL (88.06 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1478 mL | 10.7391 mL | 21.4781 mL |
| 5 mM | 0.4296 mL | 2.1478 mL | 4.2956 mL |
| 10 mM | 0.2148 mL | 1.0739 mL | 2.1478 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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Radioprotection of targeted and bystander cells by Methylproamine
Strahlenther Onkol 2015 Mar;191(3):248-55.PMID:25245467DOI:10.1007/s00066-014-0751-9.
Introduction: Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested Methylproamine for the radioprotection of both directly targeted and bystander cells. Methods: T98G glioma cells were treated with 15 μM Methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Results: Radioprotection of directly targeted T98G cells by Methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of Methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous Methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Discussion and conclusion: Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.
Protection by Methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage
Int J Radiat Biol 2011 Mar;87(3):274-83.PMID:21087168DOI:10.3109/09553002.2011.530333.
Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by Methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints. Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (¹³⁷Cs γ-rays) of cells exposed to various concentrations of Methylproamine. Uptake of Methylproamine into cell nuclei was measured in parallel. Results: The extent of radioprotection at the clonogenic survival endpoint increased with Methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of Methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM. Conclusions: These results are consistent with the hypothesis that radioprotection by Methylproamine is mediated by attenuation of the extent of initial DNA damage.
Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks
Mutat Res 2010 Oct 13;692(1-2):49-52.PMID:20732333DOI:10.1016/j.mrfmmm.2010.08.005.
Purpose: The majority of cancer patients will receive radiotherapy (RT), therefore, investigations into advances of this modality are important. Conventional RT dose intensities are limited by adverse responses in normal tissues and a primary goal is to ameliorate adverse normal tissue effects. The aim of these experiments is to further our understanding regarding the mechanism of radioprotection by the DNA minor groove binder, Methylproamine, in a cellular context at the DNA level. Materials and methods: We used immunocytochemical methods to measure the accumulation of phosphorylated H2AX (γH2AX) foci following ionizing radiation (IR) in patient-derived lymphoblastoid cells exposed to Methylproamine. Furthermore, we performed pulsed field gel electrophoresis DNA damage and repair assays to directly interrogate the action of Methylproamine on DNA in irradiated cells. Results: We found that methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence of Methylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay. Conclusions: These results suggest that Methylproamine acts by preventing the formation of DNA double-strand breaks (dsbs) and support the hypothesis that radioprotection by Methylproamine is mediated, at least in part, by decreasing initial DNA damage.
In vitro studies with Methylproamine: a potent new radioprotector
Cancer Res 2004 Feb 1;64(3):1067-70.PMID:14871839DOI:10.1158/0008-5472.can-03-2423.
New analogues of the minor groove binding ligand Hoechst 33342 have been investigated in an attempt to improve radioprotective activity. The synthesis, DNA binding, and in vitro radioprotective properties of Methylproamine, the most potent derivative, are reported. Experiments with V79 cells have shown that Methylproamine is approximately 100-fold more potent than the classical aminothiol radioprotector WR1065. The crystal structures of Methylproamine and proamine complexes with the dodecamer d(CGCGAATTCGCG)(2) confirm that the new analogues also are minor groove binders. It is proposed that the DNA-bound Methylproamine ligand acts as a reducing agent by an electron transfer mechanism, repairing transient radiation-induced oxidizing species on DNA.
Pulse radiolysis studies indicate that electron transfer is involved in radioprotection by Hoechst 33342 and Methylproamine
Int J Radiat Oncol Biol Phys 1998 Nov 1;42(4):827-31.PMID:9845105DOI:10.1016/s0360-3016(98)00316-2.
Purpose: The aim of the study was to obtain evidence to support the hypothesis that the radioprotection by DNA-binding bibenzimidazoles is due to reduction by the DNA-bound ligand of transient radiation-induced oxidizing species on DNA, by following oxidation of the ligand after pulse radiolysis. A second aim was to compare the activities of Methylproamine and Hoechst 33342 in the pulse radiolysis system, with the view to seeking a correlation with radioprotective activity. Methods: Solutions of deoxyguanosine or DNA, with or without Hoechst 33342 or Methylproamine, and containing sodium selenate and tert-butanol were subjected to pulse radiolysis, and the oxidation of the ligand followed by time-resolved spectrophotometry. Results: The initial pulse radiolysis experiments using deoxyguanosine (dG) established that pulse radiolysis of sodium selenate produces a transient oxidant SeO3*-, which oxidizes dG to a species (presumably dG*+), with spectral characteristics indistinguishable from those described in previous pulse radiolysis studies using Br2*- as the oxidant. The estimate obtained for the bimolecular rate constant (k2) for the reaction of the selenite radical with dG, was 1.2 x 10(9) M(-1) s(-1). The corresponding reaction of SeO3*- with DNA is much slower (k2 3 x 10(7) M(-1) s(-1)). Although unbound Hoechst 33342 is oxidized directly by SeO3*- (k2 2.3 x 10(9) M(-1) s(-1)), experiments with mixtures of Hoechst 33342 with an excess of dG (or DNA) indicated that ligand oxidation was mediated by dG*+ (or DNAoxid). For example, successive dilution of a DNA-Hoechst solution had little impact on the rate of ligand oxidation, consistent with an intramolecular rate-determining step. When the concentration of DNA was maintained at 1.0 mM DNA bp, increasing the concentration of the ligand resulted in a linear increase in the rate of oxidation; the increase being steeper for Methylproamine than for Hoechst 33342. Investigation of the dependence of yield of oxidized ligand on ligand occupancy also indicated that the Methylproamine was more active than Hoechst 33342, with the estimates for the range of electron transfer from the ligand to DNAoxid being 14 and 31 bp for Hoechst 33342 and Methylproamine, respectively. Conclusions: At this stage we conclude that radioprotection by these DNA-binding ligands is mediated by electron transfer, and that the improved radioprotective activity of Methylproamine may be attributable to the observed kinetic differences. However, further studies are required to confirm the correlation, and if it is sustained, pulse radiolysis could be useful in evaluating new analogues in an attempt to further improve the radioprotective properties of Methylproamine, which already has considerable clinical potential.