CP94
(Synonyms: 1,2-二乙基-3-羟基吡啶-4(1H)-酮) 目录号 : GC49059
An iron chelator
Cas No.:115900-75-9
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
CP94 is an iron chelator.1 It enhances protoporphyrin IX photobleaching and decreases in the viability of A431 squamous epithelial carcinoma cells when used at a concentration of 150 µM in combination with photodynamic therapy (PDT) mediated by the protoporphyrin IX precursors aminolevulinic acid (ALA), methyl aminolevulinate (MAL), or hexylaminolevulinate .2 CP94 (2 mg/ml in the drinking water) decreases hepatic total non-heme and ferritin-stored iron levels, as well as increases hepatic protoporphyrin levels, in mice.3 It also reduces ferrocene-induced increases in rat brain iron levels when administered at a dose of 100 mg/kg.4
1.Dobbin, P.S., Hider, R.C., Hall, A.D., et al.Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: Orally active iron chelators with clinical potentialJ. Med. Chem.36(17)2448-2458(1993) 2.Blake, E., Allen, J., and Curnow, A.The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditionsPhotodiagnosis Photodyn. Ther.10(4)575-582(2013) 3.Smith, A.G., Clothier, B., Francis, J.E., et al.Protoporphyria induced by the orally active iron chelator 1,2-diethyl-3-hydroxypyridin-4-one in C57BL/10ScSn miceBlood89(3)1045-1051(1997) 4.Ward, R.J., Dexter, D., Florence, A., et al.Brain iron in the ferrocene-loaded rat: its chelation and influence on dopamine metabolismBiochem. Pharmacol.49(12)1821-1826(1995)
| Cas No. | 115900-75-9 | SDF | |
| 别名 | 1,2-二乙基-3-羟基吡啶-4(1H)-酮 | ||
| Canonical SMILES | O=C1C=CN(CC)C(CC)=C1O | ||
| 分子式 | C9H13NO2 | 分子量 | 167.2 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 15 mg/ml,Ethanol: 30 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | -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 | 5.9809 mL | 29.9043 mL | 59.8086 mL |
| 5 mM | 1.1962 mL | 5.9809 mL | 11.9617 mL |
| 10 mM | 0.5981 mL | 2.9904 mL | 5.9809 mL |
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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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2.
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The hydroxypyridinone iron chelator CP94 can enhance PpIX-induced PDT of cultured human glioma cells
Photochem Photobiol 2010 Sep-Oct;86(5):1154-60.PMID:20573043DOI:10.1111/j.1751-1097.2010.00770.x.
Photodynamic therapy (PDT) with the pro-drugs 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) utilizes the combined interaction of a photosensitizer, light and molecular oxygen to ablate tumor tissue. To potentially increase accumulation of the photosensitizer, protoporphyrin IX (PpIX), within tumor cells an iron chelator can be employed. This study analyzed the effects of ALA/MAL-induced PDT combined with the iron chelator 1, 2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94) on the accumulation of PpIX in human glioma cells in vitro. Cells were incubated for 0, 3 and 6h with various concentrations of ALA/MAL with or without CP94 and the resulting accumulations of PpIX, which naturally fluoresces, were quantified prior to and following light irradiation. In addition, counts of viable cells were recorded. The use of CP94 in combination with ALA/MAL produced significant enhancements of PpIX fluorescence in human glioma cells. At the highest concentrations of each prodrug, CP94 enhanced PpIX fluorescence significantly at 3h for ALA and by more than 50% at 6h for MAL. Cells subsequently treated with ALA/MAL-induced PDT in combination with CP94 produced the greatest cytotoxicity. It is therefore concluded that with further study CP94 may be a useful adjuvant to photodiagnosis and/or PpIX-induced PDT treatment of glioma.
Characterization of two isomeric beta-d-glucosiduronic acids derived from 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rat liver homogenate incubates
J Pharm Pharmacol 2002 Jul;54(7):951-7.PMID:12162714DOI:10.1211/002235702760089072.
1,2-Diethyl-3-hydroxypyridin-4-one (CP94) is an orally active iron chelator with potential for use in photodynamictherapy. This investigation reports the formation and characterization of two isomeric glucuronides of CP94 in rat liver homogenate incubates. To assign the glucuronidation sites in the CP94 molecule, two O-methylated derivatives of CP94 have been synthesized. By comparing the spectral characteristics of the CP94 3-O- and 4-O-methyl derivatives with CP94 and the CP94 glucuronides formed during incubation, evidence was obtained which enabled the assignment of these two isomeric glucuronides to the 3-O-glucuronide and 4-O-glucuronide of CP94. It was found that the 3-O-glucuronide was the dominant CP94 metabolite under in-vitro conditions. In an attempt to understand the potential influence of structural variation on the glucuronidation of CP94 analogues, the 1-and 2-monoethyl derivatives of CP94 were investigated. The 2-monoethyl derivative of CP94 yielded only the 3-O-glucuronide in rat liver homogenate incubate, while no glucuronide was formed from the 1-monoethyl derivative. In addition, no glucuronide from the 3-O-methyl or 4-O-methyl derivatives of CP94 could be detected. The relevance of these findings to the development of new 3-hydroxypyridin-4-one iron chelators is discussed.
Biliary and urinary metabolic profiles of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in the rat
Drug Metab Dispos 2000 Aug;28(8):873-9.PMID:10901694doi
This study compares the biliary and urinary metabolic profiles of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), an orally active iron chelator, in the normal rat. Surprisingly, CP94 was found to form two phase II metabolites, the 3-O- and 4-O-glucuronides. These glucuronides accounted for 38 and 28% of the administered CP94 dose, in bile and urine, respectively. Unchanged CP94 accounted for 5% of the CP94 dose in both bile and urine. The 2-(1'-hydroxy) metabolite of CP94 was found to be the dominant metabolite in urine. In addition, an unstable metabolite was detected in the bile although its structure remains unknown at the present stage. The excretion of iron in bile, after administration of CP94, was found to parallel the biliary elimination of CP94 together with its hydroxylated derivatives, indicating the importance of metabolites in iron excretion.
HPLC determination of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), its iron complex [Fe(III) (CP94)3] and glucuronide conjugate [CP94-GLUC] in serum and urine of thalassaemic patients
J Pharm Biomed Anal 1994 Jul;12(7):923-30.PMID:7981322DOI:10.1016/0731-7085(94)e0027-x.
Sensitive and selective high performance liquid chromatographic (HPLC) methods for the quantification of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), its iron complex [Fe(III) (CP94)3] and glucuronide metabolite (CP94-GLUC) in urine and serum of thalassaemic patients are described. Three separate analyses are involved. The first assay quantifies both CP94 and its iron complex. This procedure requires the conversion of the iron complex to the free ligand and is carried out using diethylenetriaminepentaacetic acid (DTPA). CP94 and the internal standard, 1-propyl-2-ethyl-3-hydroxypyridin-4-one (CP95) present in either serum or urine are then extracted at pH 7.0 with dichloromethane. Extraction efficiency is 96.0 +/- 5.6% and 100 +/- 7.1% for CP94 and CP95, respectively, and 31.2 +/- 2.1% at 30 microM and 53.2 +/- 4.2% at 300 microM for the corresponding iron complex. In the second assay, samples are incubated (16 h) with beta-glucuronidase and processed as before. In this assay, the drug, its iron complex and glucuronide conjugate are measured. In the third assay the iron complex of CP94, [Fe(III) (CP94)3] is quantified. From the three separate analyses it is possible to calculate the individual concentrations of the three separate components present in serum and urine of thalassaemic patients. Calibration for both components, i.e. CP94 (assays 1 and 2) and its iron complex (assay 3) are linear with correlation coefficients > 0.99 and are reproducible over the required concentration range of 0-500 microM for the free ligand and 0-100 microM for the iron complex. The minimum quantifiable level is 0.5 microM for the free ligand and 1.0 microM for the iron complex.
The hydroxypyridinone iron chelator CP94 increases methyl-aminolevulinate-based photodynamic cell killing by increasing the generation of reactive oxygen species
Redox Biol 2016 Oct;9:90-99.PMID:27454766DOI:10.1016/j.redox.2016.07.002.
Methyl-aminolevulinate-based photodynamic therapy (MAL-PDT) is utilised clinically for the treatment of non-melanoma skin cancers and pre-cancers and the hydroxypyridinone iron chelator, CP94, has successfully been demonstrated to increase MAL-PDT efficacy in an initial clinical pilot study. However, the biochemical and photochemical processes leading to CP94-enhanced photodynamic cell death, beyond the well-documented increases in accumulation of the photosensitiser protoporphyrin IX (PpIX), have not yet been fully elucidated. This investigation demonstrated that MAL-based photodynamic cell killing of cultured human squamous carcinoma cells (A431) occurred in a predominantly necrotic manner following the generation of singlet oxygen and ROS. Augmenting MAL-based photodynamic cell killing with CP94 co-treatment resulted in increased PpIX accumulation, MitoSOX-detectable ROS generation (probably of mitochondrial origin) and necrotic cell death, but did not affect singlet oxygen generation. We also report (to our knowledge, for the first time) the detection of intracellular PpIX-generated singlet oxygen in whole cells via electron paramagnetic resonance spectroscopy in conjunction with a spin trap.