PNU-103017
目录号 : GC32327
PNU-103017是一种HIV蛋白酶抑制剂。
Cas No.:166335-18-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats and dogs are used in this study. In preclinical toxicology studies, dogs (three per gender per dose) receive 50, 100, 200, or 250 mg/kg/day, and rats (three per gender per dose) receive 80, 240, or 720 mg/kg/day PNU-103017 in a 0.5 N sodium hydroxide aqueous solution orally, twice daily, 8 and 16 h apart, respectively, for 14 days. Sequential blood specimens are collected at 0 (prior to the first daily dosing), 1, 2, 4, 8 (prior to the second daily dosing), 9, 10, 12, 16 (for dog only), and 24 h after the first daily dosing on treatment days 1, 8, and 14 for the dog and rat studies. The samples are placed into heparinized tubes, and the plasma is separated by centrifugation and stored at or below -10°C until analysis[1]. |
References: [1]. Williams MG, et al. Stereospecific determination of an HIV aspartyl protease inhibitor, PNU-103017, in rat, dog and human plasma using a Pirkle-concept high-performance liquid chromatographic column. | |
PNU-103017 is an HIV protease inhibitor.
PNU-103017 is a selective HIV aspartyl protease inhibitor under evaluation as a potential oral treatment of Acquired Immunodeficiency Diseases. PNU-103017 is a racemic mixture of two enantiomers, designated PNU-103264 (R-) and PNU-103265 (S-). The Cmax (P≤0.0349), Cmin (P≤0.0168), and Cav (P≤0.0118) are significantly higher for the (R)- than the (S)-enantiomer, showing enantioselective pharmacokinetics of PNU-103017 in the dog[1].
[1]. Williams MG, et al. Stereospecific determination of an HIV aspartyl protease inhibitor, PNU-103017, in rat, dog and human plasma using a Pirkle-concept high-performance liquid chromatographic column.
| Cas No. | 166335-18-8 | SDF | |
| Canonical SMILES | O=S(C1=CC=C(C#N)C=C1)(NC2=CC=CC(C(C3CC3)C4=C(O)C(CCCCCC5)=C5OC4=O)=C2)=O | ||
| 分子式 | C28H28N2O5S | 分子量 | 504.6 |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9818 mL | 9.9088 mL | 19.8177 mL |
| 5 mM | 0.3964 mL | 1.9818 mL | 3.9635 mL |
| 10 mM | 0.1982 mL | 0.9909 mL | 1.9818 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。
Species-dependent enantioselective pharmacokinetics of PNU-103017, a pyrone HIV protease inhibitor
Chirality 1998;10(3):210-6.PMID:9499572DOI:10.1002/(SICI)1520-636X(1998)10:3<210::AID-CHIR2>3.0.CO;2-D.
PNU-103017, 4-Cyano-N-(3-(cyclopropyl(5,6,7,8,9,10-hexahydro-4-hydroxy- 2-oxo-2H-cycloocta(b) pyran-3-yl)methyl)phenyl)-benzenesulfonamide, is a selective HIV aspartyl protease inhibitor under evaluation as a potential oral treatment of Acquired Immunodeficiency Diseases. PNU-103017 is a racemic mixture of two enantiomers, designated PNU-103264 (R-) and PNU-103265 (S-). Stereoselective pharmacokinetics of the two enantiomers of PNU-103017 were observed in the dog, rat, and human after single and multiple dose administration of the racemate and were apparently species-dependent. Mean enantiomeric ratios of plasma concentrations (R-/S-) at each time point were greater than 1 in the dog, ranging from 1.22 to 3.06, but less than 1 in the rat and in the human, ranging from 0.44 to 0.80 and 0.23 to 0.73, respectively. A trend towards increased or decreased (farther from 1:1, R-/S-) enantiomeric ratio of plasma concentrations with time after each administration was also observed. The enantiomeric ratio remained unchanged after multiple dose administration in the rat, dog, and human although enzyme induction and increased plasma clearance were observed for both enantiomers.
Stereospecific determination of an HIV aspartyl protease inhibitor, PNU-103017, in rat, dog and human plasma using a Pirkle-concept high-performance liquid chromatographic column
J Chromatogr B Biomed Sci Appl 1997 Jun 20;694(1):169-77.PMID:9234860DOI:10.1016/s0378-4347(97)00121-7.
A sensitive stereospecific high-performance liquid chromatographic assay for the quantitation of the enantiomers of 4-cyano-N-(3-(cyclopropyl-(5,6,7,8,9,10-hexahydro-4-hydroxy-2-oxo-2H- cycloocta(b)pyran-3-yl)methyl)phenyl)benzenesulfonamide (PNU-103017) (I), an HIV protease inhibitor, in plasma of rat, dog and human was developed. The procedure involved an acetonitrile-aided protein precipitation followed by solid-phase extraction (SPE) of I from plasma into ethanol. Stereospecific separation was accomplished on a Pirkle-concept chiral column (Regis S,S-Whelk-01, 250x4.6 mm I.D.) with a mobile phase of absolute ethanol-0.1% acetic acid in hexane (30:70, v/v). The eluate was monitored by UV absorbance (295 nm). Linear calibration curves were obtained in the range of 0.2 to 500 microM, with a lower limit of quantitation of 0.1-0.2 microM for both enantiomers in either rat, dog or human plasma. Intra- and inter-assay precision and assay accuracy were demonstrated to be acceptable for the stereoselective pharmacokinetic analysis of I in plasma.
Equilibrium distribution of HIV antiviral drugs into human peripheral blood mononuclear cells (PBMC) is controlled by free drug concentration in the extracellular medium
J Pharm Biomed Anal 1999 Mar;19(3-4):399-411.PMID:10704105DOI:10.1016/s0731-7085(98)00143-5.
Effect of protein binding on the equilibrium distribution of selected HIV antiviral drugs into isolated human peripheral blood mononuclear cells (PBMC, mainly lymphocytes) was investigated. Human PBMC from a single healthy human donor were isolated, purified, and cryopreserved. Uptake of non-peptide HIV-1 protease inhibitors PNU-96988 and PNU-103017 by these cells in vitro was evaluated as a function of increasing concentration of human serum in the cell incubation media. Both PNU-96988 and PNU-103017 were extensively bound to serum proteins. Uptake/efflux kinetics were very rapid such that accumulation by the cells was thermodynamically, not kinetically, controlled. Accumulation by human PBMCs in vitro was directly proportional to the free and not the total drug concentration in the media. For comparative purposes, the serum protein binding effect on the distribution of two HIV reverse transcriptase (RT) inhibitors, delavirdine (RESCRIPTOR) and zidovudine (AZT), was also evaluated. Like the HIV-1 protease inhibitors, delavirdine was found to be extensively associated with serum proteins and its accumulation by human PBMCs in vitro to be proportional to the free and not total drug concentration. In contrast, AZT was not bound to serum proteins to any significant extent. The uptake of this drug by human PBMCs in vitro was independent of serum concentration. However, the intrinsic cellular accumulation of PNU-96988, PNU-103017 and delavirdine were all greater than AZT. Thus, the extent to which drugs uptake by cells is affected by serum appears proportional to the binding affinity of the serum proteins for the drug.