CGP 65015
目录号 : GC30589
CGP65015是一种可口服的铁螯合剂，可以清除铁沉积。
Cas No.:189564-33-8
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
Animal experiment: | Marmosets[1]To approximate the iron status of thalassaemic patients in the marmosets, the animals are iron-overloaded by three i.p. injections of iron (III) hydroxide polyisomaltose at 14-d intervals (200 mg/kg twice and 100 mg/kg at the third injection). Prior to the first exposure to an iron chelator (CGP 65015), the marmosets are rested for at least 8 weeks in order to allow definite distribution of the injected iron into all storage compartments. CGP 65015 is dispersed in 40% aqueous Cremophor RH 40 for oral administration of 150 μmol IBE/kg. All dosages are expressed in terms of 'iron binding equivalents' (IBE) which take into account the stoichiometry of the chelator in the iron complex, i.e. 150 μmol IBE correspond to 150, 300 and 450 μmol of a mono-, bi- and tridentate chelator respectively. The standard dose is 150 μmol iron binding equivalents (IBE) per kg body weight. The applied volume is 5 mL/kg body weight[1]. |
References: [1]. Sergejew T, et al. Chelator-induced iron excretion in iron-overloaded marmosets. Br J Haematol. 2000 Sep;110(4):985-92. | |
CGP 65015 is an oral iron chelator, which can mobilize iron deposits.
CGP 65015 is an oral iron chelator[1].
CGP65015 (150 μmol IBE/kg p.o. on d0) dramatically increases the urinary and faecal iron clearance, and still enhances iron elimination during the second post-treatment day in iron-overloaded marmosets[1].
[1]. Sergejew T, et al. Chelator-induced iron excretion in iron-overloaded marmosets. Br J Haematol. 2000 Sep;110(4):985-92.
| Cas No. | 189564-33-8 | SDF | |
| Canonical SMILES | O=C1C(O)=C(C(O)C2=CC=CC=C2)N(CCO)C=C1 | ||
| 分子式 | C14H15NO4 | 分子量 | 261.27 |
| 溶解度 | Soluble in DMSO | 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 | 3.8275 mL | 19.1373 mL | 38.2746 mL |
| 5 mM | 0.7655 mL | 3.8275 mL | 7.6549 mL |
| 10 mM | 0.3827 mL | 1.9137 mL | 3.8275 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。
In vitro and in situ permeability of a 'second generation' hydroxypyridinone oral iron chelator: correlation with physico-chemical properties and oral activity
Purpose: The in vitro and in situ transport of CGP 65015 ((+)-3-hydroxy-1-(2-hydroxyethyl)-2-hydroxyphenyl-methyl-1H-pyridin-4-on e), a novel oral iron chelator, is described. The predictive power of these data in assessing intestinal absorption in man is described. Methods: Caco-2 epithelial monolayer and in situ rat jejunum perfusion intestinal permeability models were utilized. In vivo iron excretion and preliminary animal pharmacokinetic experiments were described. Ionization constants and octanol/aqueous partition coefficients were measured potentiometrically. Solubilities and intrinsic dissolution rates were determined using standard procedures. Results: Caco-2 cell (Papp approximately 0.25 x 10(-6) cm x s(-1)) and rat jejunum (Pw approximately 0.4) permeabilities of CGP 65015 were determined. The log D(pH 7.4) of CGP 65015 was 0.58 and its aqueous solubility was < 0.5 mg x ml(-1) (pH 3-9). The intrinsic dissolution rate of CGP 65015 in USP simulated intestinal fluid was 0.012 mg x min(-1) x cm(-2). CGP 65015 promotes iron excretion effectively and dose dependently in animals. Conclusions: Caco-2 and rat intestinal permeabilities predict incomplete oral absorption of CGP 65015 in man. Preliminary rat pharmacokinetics support this. Physico-chemical data are, also, in line and suggest that CGP 65015 may, in addition, be solubility/dissolution rate limited in vivo. Nevertheless, early animal pharmacological data demonstrate that CGP 65015 is a viable oral iron chelator candidate.
Chelator-induced iron excretion in iron-overloaded marmosets
In order to test new orally active iron chelators in a predictive way, a primate model has been developed. This model makes use of the marmoset monkey (Callithrix jacchus) and its overall design is similar to a previously reported monkey model. However, this new model enables a higher compound throughput and requires lower amounts of test compound because the animals are much easier to handle and have much lower body weights. The marmosets were iron-overloaded by three intraperitoneal injections of iron (III) hydroxide polyisomaltose. For the iron-balance studies, the animals were kept in metabolic cages and were maintained on a low-iron diet in order to reduce faecal background. After compound administration, the excretion of iron in urine and faeces was followed for 2 d. A series of well-known chelators was tested for validation of the model. In particular, comparison of the iron-clearing properties of DFO, L1, CP94 and HBED in marmosets and humans demonstrated the predictive value of the model and justify our expectation that if iron chelators such as CGP65015, ICL670A and CGP75254A are active in marmosets, they will be active in humans as well.