CP102
目录号 : GC49060
An iron chelator
Cas No.:126055-13-8
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
CP102 is an iron chelator.1,2 It decreases hepatic total non-heme and ferritin-stored iron levels in mice when administered in the drinking water at a concentration of 2 mg/ml.2
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.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)
| Cas No. | 126055-13-8 | SDF | |
| Canonical SMILES | O=C1C=CN(CCO)C(CC)=C1O | ||
| 分子式 | C9H13NO3 | 分子量 | 183.2 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,PBS (pH 7.2): 1 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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| 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 | 5.4585 mL | 27.2926 mL | 54.5852 mL |
| 5 mM | 1.0917 mL | 5.4585 mL | 10.917 mL |
| 10 mM | 0.5459 mL | 2.7293 mL | 5.4585 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。
Metabolism and pharmacokinetics of 1-(2'-hydroxy-ethyl)- and 1-(3'-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-ones in the rat
Eur J Drug Metab Pharmacokinet 1996 Jan-Mar;21(1):33-41.PMID:8839676DOI:10.1007/BF03190276.
The urinary recovery (p.o.) and pharmacokinetics (i.v. and p.o.) of two compounds from the 1-hydroxyalkyl-3-hydroxypyridin-4-one series. 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridine-4-one (CP102) and 1-(3'-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-one (CP106) were studied in the rat. The pharmacokinetics of the 1-carboxyethyl metabolite (CP110) of CP106 was also studied (i.v.). CP102 was not metabolised to any considerable extent with 68.4 +/- 12.2% of the administered dose recovered unchanged in rat urine. In contrast, CP106 undergoes extensive phase I metabolism to form the 1-carboxyalkyl metabolite which accounted for 56.4 +/- 11% of the administered dose with 22.0 +/- 1.0% as unchanged drug. Intravenous and oral pharmacokinetics of CP102 and CP106 were studied in the rat at 450 mumols/kg. The AUCs of CP102 and CP106 after bolus i.v. infusion were 458 +/- 38 and 171 +/- 20 mumols/l.h. The AUC values after bolus oral administration were 318 +/- 46 and 77 +/- 18 mumols/l.h, respectively, with corresponding bioavailabilities (F) of 0.69 and 0.45. The Cmax of CP102 and CP106 were 142 +/- 25 and 70 +/- 15 mumols/l with Tmax values of 0.75 +/- 0.15 and 0.50 +/- 0.10 h, respectively. The CL, MRT and Vdss of CP102 was 1.00 +/- 0.09 l/kg/h, 0.92 +/- 0.04 h and 0.91 +/- 0.05 l/kg, respectively. The corresponding pharmacokinetic parameters for CP106 were 2.64 +/- 0.20 l/kg/h, 0.42 +/- 0.12 h and 1.12 +/- 0.26 l/kg, respectively. Renal clearance (CLR) of CP102 and CP106 were 1.00 +/- 0.18 l/kg and 1.27 +/- 0.31 l/kg respectively. The pharmacokinetics of CP110, which was conducted by the i.v. route only at a dose of 450 mumols/kg, had an AUC of 289 +/- 46 mumols/l.h, CL of 1.56 +/- 0.29 l/kg/h, MRT of 0.25 +/- 0.09 h and Vdss of 0.40 +/- 0.13 l/kg, respectively.
Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat
Drug Metab Dispos 1997 Mar;25(3):332-9.PMID:9172951doi
Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl]-2-ethyl-3-hydroxypyridin-4-one (CP117) were studied in the rat. Urinary recovery studies were conducted in normal (oral and intravenous) and iron-overloaded rats (500 mg Fe/kg body weight; oral only). In normal rats, the majority of the dose recovered in the urine was as the hydrophilic metabolite, CP102, accounting for 69.7 +/- 9.4% (oral) and 80.7 +/- 7.9% (intravenous) of the administered dose. There was, however, a dramatic decrease in the amount of CP102 recovered (47.7 +/- 5.9%) (p < or = 0.05) in the iron-loaded group of animals. The amount of CP102 glucuronide conjugate recovered in the normal and iron-overloaded rats after oral administration of CP117 did not differ significantly with values of 6.5 +/- 2.5% and 7.1 +/- 2.5%, respectively. There was, however, a significant increase in CP102 glucuronide conjugate (13.7 +/- 3.0%) (p < or = 0.05) after intravenous administration of CP117. Urinary iron content was determined in the iron-overloaded and normal (oral) animals. Negligible levels of the CP117 iron complex and only 0.6 +/- 0.2% was present as the corresponding CP102 complex in the urine of normal animals. Less than 0.1% of the administered dose was recovered as CP117-iron complex and only 1.3 +/- 0.2% as CP102-iron complex in the iron-overloaded animals. Total recovery of the administered dose was significantly different between normal (po) and iron-overloaded groups of animals, decreasing from 76.4 +/- 11.7% to 57.2 +/- 9.6%, respectively (p < or = 0.05). There was no significant difference between the two routes of administration in normal animals, with total recovery of the administered dose of CP117 being 96.1 +/- 9.1% by the intravenous route. Intravenous and oral pharmacokinetics of CP117 was studied in the rat at a fixed dose of 450 mumol/kg. The AUC of the drug was 43.2 +/- 9.1 mumol/liter . hr and 4.1 +/- 1.8 mumol/liter.hr via the intravenous and oral routes, respectively, thus indicating that the systemic bioavailability of the drug is < 10%. Pharmacokinetic parameters of the drug determined by the intravenous route indicate that CP117 has a plasma clearance of 10.9 +/- 3.0 mumol/liter.hr, a mean residence time of 0.14 +/- 0.05 hr, and volume of distribution at steady-state of 1.54 +/- 0.52 liters.kg-1. The Cmax and tmax of CP117 were 12.1 +/- 2.5 mumol/liter and 7.0 +/- 2.7 min, respectively. The AUC of the main metabolite, CP102, decreased from 425.3 +/- 8.5 mumol/liter.hr to 282 +/- 31 mumol/liter.hr via the intravenous and oral routes, which is presumed to reflect differences in hepatic extraction and routes of elimination of the drug. Parallel absorption studies conducted using the in situ isolated rat gut loop model indicate that the majority of the administered dose was absorbed intact as the parent drug with mesenteric vein AUC values of 3.1 +/- 1.7 mmol/liter.hr and 0.3 +/- 0.04 mmol/liter.hr for CP117 and CP102, respectively.
Synthesis, physicochemical properties and biological evaluation of aromatic ester prodrugs of 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP102): orally active iron chelators with clinical potential
J Pharm Pharmacol 1999 May;51(5):555-64.PMID:10411215DOI:10.1211/0022357991772655.
The synthesis of seven aromatic ester derivatives of 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one is described. These ester prodrugs have been designed to target iron chelators to the liver, the major iron storage organ. In principle this should improve chelation efficacy and minimize toxicity. The distribution coefficients of these ester prodrugs between 1-octanol and MOPS buffer pH 7.4 were measured together with their rates of hydrolysis at pH 2 and pH 7.4, in rat blood and liver homogenate. Esters with heteroaromatic acid moieties were found to be less stable than benzoyl analogues. The in-vivo iron mobilisation efficacy of these ester prodrugs has been compared with that of the parent drug using a 59Fe-ferritin loaded rat model. Many prodrugs were found to enhance the ability of the parent hydroxypyridinone to facilitate 59Fe excretion. However, not all prodrugs provided increased efficacy, demonstrating that lipophilicity is not the only factor which influences drug efficacy. Furthermore, no clear correlation between efficacy and susceptibility to hydrolysis was detected. The picolinic and nicotinic ester derivatives appear to offer the best potential as prodrugs as they have a relatively low LogP value and yet lead to enhanced efficacy over the parent hydroxypyridinone.
Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats
J Hepatol 1997 Jul;27(1):176-84.PMID:9252093DOI:10.1016/s0168-8278(97)80299-1.
Background/aims: It is well documented that levels of plasma non-transferrin-bound iron (NTBI), a particularly toxic form of iron, are increased in iron overload disorders. In light of the pathogenetic importance of NTBI in chronic iron overload, we have studied the ability of new orally active iron chelators to promote the biliary excretion of iron originating as plasma 55Fe-NTBI. Methods: Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of 55Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a single intragastric dose of iron chelator. These chelators were the novel hydroxypyridin-4-one compounds CP102, CP41, and their respective pro-drugs CP117 and CP165. Results: The cumulative recovery of 55Fe in bile of normal rats was increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165, respectively. In iron overloaded rats, these compounds increased the cumulative recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had a choleretic effect, were metabolized by the liver as demonstrated by HPLC study of bile, and were not cytotoxic since normal plasma transaminase levels were maintained at the end of the experiments. Conclusions: These chelators have potential interest for the treatment of iron overload conditions and may offer advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1).
Protoporphyria induced by the orally active iron chelator 1,2-diethyl-3-hydroxypyridin-4-one in C57BL/10ScSn mice
Blood 1997 Feb 1;89(3):1045-51.PMID:9028337doi
Administration in the drinking water of the orally-active iron chelator 1,2-diethyl-3-hydroxypyridin-4-one (CP94) to C57BL/10ScSn mice caused the development of hepatic protoporphyria. This was detected after 1 week and continued as long as the chelator was given (15 weeks). The more hydrophilic 1,2-dimethyl- and 1-hydroxyethyl,2-ethyl-analogues (CP20 and CP102) were also tested, but they were both inactive in inducing accumulation of protoporphyrin in the liver. Restriction of in vivo iron supply for ferrochelatase seemed a likely mode of action, but an approximately 30% decrease in activity of this enzyme was also observed when measured in vitro. Extracts of livers from mice given CP20, CP94, and CP102 showed no potential to inhibit mouse ferrochelatase, in contrast to the findings with an extract from mice treated with the known porphyrogenic chemical 4-ethyl-3, 5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine, indicating that ferrochelatase inhibition did not occur by the formation of an N-ethyl-protoporphyrin derived from metabolism by cytochrome P450, CP20, CP94, CP102, and CP117 (the pivoyl ester of CP102) all caused significant depression of the levels of ferritin-iron and total nonheme iron, but only CP94 caused the significant accumulation of protoporphyrin. Protoporphyria did not occur with iron overloaded C57BL/10ScSn mice or in SWR mice that had elevated basal iron status. Although the protoporphyrin had only a small effect on the total levels of the hemoprotein cytochrome P450 in C57BL/10ScSn mice, the activity of the CYP2B isoforms of cytochrome P450 was actually induced in both strains. The results show that CP94 could cause protoporphyria in individuals of low iron status, perhaps through specifically targeting particular iron pools available to ferrochelatase and by concomitantly stimulating heme synthesis.