6-Mercaptopurine hydrate
(Synonyms: 6-巯基嘌呤 一水合物; Mercaptopurine hydrate; 6-MP hydrate) 目录号 : GC32975
An inhibitor of purine synthesis and interconversion
Cas No.:6112-76-1
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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | L6 myotubes are treated with DMSO control or 6-Mercaptopurine hydrate (6-MP) for 24 h, with the final 3 h of incubation including treatments in serum-free DMEM, and further incubated in the absence or presence of 100 nM insulin for 60 min at 37°C. Then, protein lysates (50 μg) are collected and subjected to SDS-PAGE. The proteins are finally quantified by densitometric analysis of scanned films using Image J software[2]. |
Cell experiment: | Cell viability is measured using Cell Viability Assay. L6 skeletal muscle cells are seeded in 96-well plates at a density of 10,000 cells/well and differentiated into myotubes within 7 days. Cells are treated with different doses of 6-Mercaptopurine hydrate (6-MP) for 24 h before the assay. For analysis of cell viability, plates are equilibrated at room temperature for 30 min; 50 μL of Cell Titer-Glo reagent is added to each well, and plates are mixed for 12 min on an orbital shaker. Luminescence is quantified using a luminometer[2]. |
Animal experiment: | Around thirteen-week-old pregnant rats are used in this study. The animals are housed individually in wire-mesh cages in an air-conditioned room (temperature, 23±3°C; humidity, 50±20%; ventilation, 10 times/hour; lighting, 12 h light to12 h dark cycle) and are given pelleted diet and water ad libitum. In the experiment, fifteen pregnant rats are injected i.p. with 50 mg/kg 6-Mercaptopurine hydrate (6-MP) on E13, and three dams each are sacrificed by exsanguination from the abdominal aorta under ether anesthesia at 12, 24, 36, 48, and 72 h. Fetuses are collected from each dam by Caesarean section. As controls, fifteen pregnant rats are injected i.p. with 2.0% methylcellulose solution in distilled water at E13, and three dams are sacrificed at each of the same time-points[3]. |
References: [1]. Sahasranaman S, et al. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. | |
6-Mercaptopurine (6-MP) is an inhibitor of purine synthesis and interconversion.1 It is rapidly converted to 6-mercaptopurine ribonucleoside-5'-monophosphate, which inhibits phosphoribosyl pyrophosphate (PRPP) amidotransferase, the rate-limiting enzyme in purine synthesis. It also inhibits the conversion of IMP to adenylosuccinic acid and xanthylic acid and blocks AMP formation in vitro. 6-MP (30 mg/kg) inhibits growth of sarcoma 180, adenocarcinoma E 0771, and adenocarcinoma 755 tumors and reduces the size of leukemia L1210 subcutaneous growths in mice.2 It also decreases delayed-type hypersensitivity and thyroid inflammation in a guinea pig model of thyroiditis when administered pre- or post-disease onset.3 Formulations containing mercaptopurine have been used for maintenance therapy in patients with acute lymphoblastic leukemia.4
1.Brockman, R.W.Biochemical aspects of mercaptopurine inhibition and resistanceCancer Res.23(8)1191-1201(1963) 2.Skipper, H.E., Thomson, J.R., Elion, G.B., et al.Observations on the anticancer activity of 6-mercaptopurineCancer Res.14(4)294-298(1954) 3.Spiegelberg, H.L., and Miescher, P.A.The effect of 6-mercaptopurine and aminopterin on experimental immune thyroiditis in guinea pigsJ. Exp. Med.118(5)869-890(1963) 4.Alsous, M., Abu Farha, R., Alefishat, E., et al.Adherence to 6-mercaptopurine in children and adolescents with acute lymphoblastic leukemiaPLoS One12(9)e0183119(2017)
| Cas No. | 6112-76-1 | SDF | |
| 别名 | 6-巯基嘌呤 一水合物; Mercaptopurine hydrate; 6-MP hydrate | ||
| Canonical SMILES | S=C1NC=NC2=C1NC=N2.O | ||
| 分子式 | C5H6N4OS | 分子量 | 170.19 |
| 溶解度 | DMSO : 32 mg/mL (188.03 mM) | 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 | 5.8758 mL | 29.3789 mL | 58.7579 mL |
| 5 mM | 1.1752 mL | 5.8758 mL | 11.7516 mL |
| 10 mM | 0.5876 mL | 2.9379 mL | 5.8758 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。
Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells
Nanomaterials (Basel) 2022 Nov 16;12(22):4029.PMID:36432314DOI:10.3390/nano12224029.
6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.
6-Mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic treatment without hepatotoxicity and nephrotoxicity
Cancer Invest 2007 Mar;25(2):117-23.PMID:17453823DOI:10.1080/07357900701224862.
6-Mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.
XRD, vibrational spectra and quantum chemical studies of an anticancer drug: 6-Mercaptopurine
Spectrochim Acta A Mol Biomol Spectrosc 2015 Jul 5;146:204-13.PMID:25813177DOI:10.1016/j.saa.2015.02.104.
The single crystal of the hydrated anticancer drug, 6-Mercaptopurine (6-MP), has been grown by slow evaporation technique under room temperature. The structure was determined by single crystal X-ray diffraction. The vibrational spectral analysis was carried out using Laser Raman and FT-IR spectroscopy in the range of 3300-100 and 4000-400 cm(-1). The single crystal X-ray studies shows that the crystal packing is dominated by N-H⋯O and O-H⋯N classical hydrogen bonds leading to a hydrogen bonded ensemble. This classical hydrogen bonds were further connected through O-H⋯S hydrogen bond to form two primary ring R4(4)(16) and R4(4)(12) motifs. These two primary ring motifs are interlinked with each other to build a ladder like structure. These ladders are connected through N-H⋯N hydrogen bond along c-axis of the unit cell through chain C(5) motifs. Further, the strength of the hydrogen bonds is studied through vibrational spectral measurements. The shifting of bands due to the intermolecular interactions was also analyzed in the solid crystalline state. Geometrical optimizations of the drug molecule were done by Density Functional Theory (DFT) using the B3LYP function and Hartree-Fock (HF) level with 6-311++G(d,p) basis set. The optimized molecular geometry and computed vibrational spectra are compared with experimental results which show significant agreement. The natural bond orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and intramolecular charge transfer (ICT). The chemical hardness, electro-negativity and chemical potential of the molecule are carried out by HOMO-LUMO plot. In which, the frontier orbitals has lower band gap value indicating the possible pharmaceutical activity of the molecule.
Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate
Chem Commun (Camb) 2016 Apr 18;52(30):5281-4.PMID:27002860DOI:10.1039/c6cc00424e.
Structural and thermal data were obtained for a novel hemihydrate of 6-Mercaptopurine. The hemihydrate shows increased solubility and bioavailability when compared to the monohydrate form, better stability against conversion in aqueous media than the anhydrate form, and a dehydration temperature of 240 °C, the highest of any known hydrate crystal.
Study of azathioprine encapsulation into liposomes
J Microencapsul 1998 Jul-Aug;15(4):485-94.PMID:9651870DOI:10.3109/02652049809006875.
The factors influencing the encapsulation of azathioprine (AZA) into liposomes were investigated to find out the conditions for its optimal entrapment. Similar studies for comparison were also carried out on 6-Mercaptopurine (6-MP), of which AZA is a prodrug. AZA and also 6-MP show higher encapsulation efficiencies in MLVs as compared to LUVs. Variation in phospholipid composition does not seem to affect the loading capacity of either of the two drugs. The encapsulation efficiency of both the drugs improves upon addition of cholesterol in the bilayer, but the effect is seen only up to 30% cholesterol. Thereafter the effect becomes constant. AZA shows better incorporation in the positively charged liposomes as compared to those with neutral or negative charge. The entrapment of 6-MP is, however, found to be independent of the charge on the liposomes. Entrapment efficiency for both the drugs markedly depends on the pH of the hydration medium, yielding better entrapment efficiencies at high pH values. The rise in solute concentration initially causes increase in the entrapment of the two drugs which is followed by a decreasing phase.