6(5H)-Phenanthridinone
(Synonyms: 6(5H)-菲啶酮) 目录号 : GC45772
An inhibitor of PARP1 and 2
Cas No.:1015-89-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 (EC50s = 10.2 and 36.3 μM, respectively, in yeast cells expressing the human enzymes).1 It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells when used at a concentration of 50 μM.2 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes.3 In vivo, 6(5H)-phenanthridinone (60 mg/kg) reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels in a mouse model of carbon tetrachloride-induced hepatotoxicity when administered at a dose of 10 mg/kg.4
|1. Perkins, E., Sun, D., Nguyen, A., et al. Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast. Cancer Res. 61(10), 4175-4183 (2001).|2. Weltin, D., Holl, V., Hyun, J.W., et al. Effect of 6(5H)-phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma cells. Int. J. Radiat. Biol. 72(6), 685-692 (1997).|3. Chiarugi, A. Inhibitors of poly(ADP-ribose) polymerase-1 suppress transcriptional activation in lymphocytes and ameliorate autoimmune encephalomyelitis in rats. Br. J. Pharmacol. 137(6), 761-770 (2002).|4. Banasik, M., Stedeford, T., Strosznajder, R.P., et al. Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride. J. Enzyme Inhib. Med. Chem. 26(6), 883-889 (2011).
| Cas No. | 1015-89-0 | SDF | |
| 别名 | 6(5H)-菲啶酮 | ||
| Canonical SMILES | O=C1C2=C(C=CC=C2)C3=CC=CC=C3N1 | ||
| 分子式 | C13H9NO | 分子量 | 195.2 |
| 溶解度 | DMF: 1mg/mL,DMF:PBS (pH 7.2) (1:5): 0.16mg/mL | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.123 mL | 25.6148 mL | 51.2295 mL |
| 5 mM | 1.0246 mL | 5.123 mL | 10.2459 mL |
| 10 mM | 0.5123 mL | 2.5615 mL | 5.123 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Immunosuppressive activities of 6(5H)-Phenanthridinone, a new poly(ADP-ribose)polymerase inhibitor
Int J Immunopharmacol 1995 Apr;17(4):265-71.PMID:7672878DOI:10.1016/0192-0561(95)00007-o.
6(5H)-Phenanthridinone, a recently identified poly(ADP-ribose)polymerase (PARP) inhibitor, is able, at micromolar concentrations, to inhibit concanavalin A-induced lymphocyte proliferation and to potentiate the effect of gamma radiation upon murine spleen cells. When added at the onset of a mixed lymphocyte culture, this compound strongly depresses the induction of primary allogeneic (anti-H2k) cytotoxic T-lymphocytes (CTLs). Lymphokine-activated killer (LAK) induction was also found to be impaired by the PARP inhibitor. Taken together, these results clearly indicate that PARP plays a key-role in immune reactions involving cytotoxicity and that 6(5H)-Phenanthridinone could be considered as a potent immunomodulator.
Effect of 6(5H)-Phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma cells
Int J Radiat Biol 1997 Dec;72(6):685-92.PMID:9416791DOI:10.1080/095530097142843.
The ability of 6(5H)-Phenanthridinone (Phen), a new potent poly(ADP-ribose)polymerase (PARP) inhibitor, to potentiate the effect of ionizing radiation on tumour cells was evaluated. RDM4 murine lymphoma cells were irradiated using a 60Co panoramic source and then examined for their growth, cell cycle distribution and apoptosis. Phen (100 microM) was found to inhibit more than 90% of the PARP activity in control and irradiated cells. Cell proliferation was assessed using Alamar Blue, a new fluorometric assay. Phen was found to sharply increase the radiation-induced inhibition of cell proliferation. Indeed, at 2.5 Gy the relative cell number of Phen-treated cells was 60% below control levels. At the same radiation dose, the G2M arrest was also significantly reinforced by the addition of Phen. Furthermore, this PARP inhibitor was shown to significantly increase the amount of DNA fragmentation as revealed by the DNA migration pattern in agarose gel electrophoresis. Comparable results were obtained with 3-aminobenzamide, another PARP inhibitor, but at concentrations 200-fold higher. Taken together, these results indicate the potential interest of Phen as a valuable pharmacological probe for investigating the role of PARP in cellular responses to radiation. They also suggest a possible use of Phen as an adjuvant in radiotherapy.
Effects of proximity on the relaxation dynamics of flindersine and 6(5H)-Phenanthridinone
J Phys Chem A 2007 Jan 18;111(2):193-200.PMID:17214453DOI:10.1021/jp0646426.
The role played by the carbonyl group in the antenna system of a naturally occurring photochromic chromene, flindersine (FL), has been experimentally investigated and compared with that of a carbonyl group present in a structurally related unreactive heterocyclic compound, 6(5H)-Phenanthridinone (PH). Through stationary and time-resolved absorption and emission techniques, the excited-state relaxation dynamics after UV irradiation were determined for FL and PH. The presence of a carbonyl group in both compounds entails the existence of two close-lying, strongly coupled electronic excited states, having n,pi* and pi,pi* character, respectively. Their coupling can be modulated by a careful choice of the solvent proticity and temperature. Moreover, in the case of strong coupling between the n,pi* and pi,pi* states, we have proved that the relaxation dynamics can involve transitions in which the upper of the coupled states acts as an intermediate for radiationless decay, bypassing the lowest emissive state, whereby the fluorescence quantum yield becomes a function of the excitation wavelength.
Effects of 6(5H)-Phenanthridinone, an inhibitor of poly(ADP-ribose)polymerase-1 activity (PARP-1), on locomotor networks of the rat isolated spinal cord
Cell Mol Neurobiol 2011 May;31(4):503-8.PMID:21331624DOI:10.1007/s10571-011-9661-x.
Excitotoxicity is considered to be a major pathophysiological mechanism responsible for extensive neuronal death after acute spinal injury. The chief effector of such a neuronal death is thought to be the hyperactivation of intracellular PARP-1 that leads to cell energy depletion and DNA damage with the manifestation of non-apoptotic cell death termed parthanatos. An in vitro lesion model using the neonatal rat spinal cord has recently shown PARP-1 overactivity to be closely related to neuronal losses after an excitotoxic challenge by kainate: in this system the PARP-1 inhibitor 6(5H)-Phenanthridinone (PHE) appeared to be a moderate histological neuroprotector. This article investigated whether PHE could actually preserve the function of locomotor networks in vitro from excitotoxicity. Bath-applied PHE (after a 60 min kainate application) failed to recover locomotor network function 24 h later. When the PHE administration was advanced by 30 min (during the administration of kainate), locomotor function could still not be recovered, while basic network rhythmicity persisted. Histochemical analysis showed that, even if the number of surviving neurons was improved with this protocol, it had failed to reach the threshold of minimal network membership necessary for expressing locomotor patterns. These results suggest that PARP-1 hyperactivity was a rapid onset mechanism of neuronal loss after an excitotoxic challenge and that more selective and faster-acting PARP-1 inhibitors are warranted to explore their potential neuroprotective role.
Modulation of the antiproliferative activity of anticancer drugs in hematopoietic tumor cell lines by the poly(ADP-ribose) polymerase inhibitor 6(5H)-Phenanthridinone
Anticancer Res 2000 Sep-Oct;20(5A):3233-41.PMID:11062748doi
Poly (ADP-ribose) polymerase (PARP) is involved in the cellular responses to genotoxic damage and its inhibition has been proposed as potentiating anticancer drug activity. Here, we evaluated the ability of the PARP inhibitor, 6(5H)-Phenanthridinone, to modulate the antiproliferative activity of bleomycin, carmustin and doxorubicin in a murine (RDM4) and a human (U937) lymphoma cell lines. 6(5H)-Phenanthridinone was shown to suppress PARP activity with the same potency in both cell lines. At 25 microM, this compound potentiated the activity of carmustin in RDM4 but not in U937 cells. In contrast, 6(5H)-Phenanthridinone failed to affect the doxorubicin toxicity in murine lymphoma cells, whereas it prevented the cytotoxicity of this drug in the human cell line. Altogether, these findings indicated that 6(5H)-Phenanthridinone modulates the cytotoxicity of anticancer agents differently according to the cell type and the drug. Therefore, this PARP inhibitor could be considered as the prototype of a new class of adjuncts in cancer chemotherapy.