PMEDAP
目录号 : GC63302
PMEDAP 是人类免疫缺陷病毒 (HIV) 复制的有效抑制剂。PMEDAP 具有抗小鼠巨细胞病毒 (MCMV) 活性。PMEDAP 是莫罗尼鼠肉瘤病毒 (MSV) 诱导的肿瘤形成和相关死亡率的有效抑制剂。
Cas No.:113852-41-8
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
PMEDAP is a potent inhibitor of human immunodeficiency virus (HIV) replication. PMEDAP has anti-murine cytomegalovirus (MCMV) activity. PMEDAP is a very potent inhibitor of Moloney murine sarcoma virus (MSV)-induced tumor formation and associated mortality[1][2].
PMEDAP (0.25-5 mg/kg; IP; daily; starting on the day of MSV-infected and continuing for an additional four days) causes a dose-dependent suppression of tumor formation and mortality in newborn mice inoculated with MSV[1].
[1]. Neyts J, et al. Activity of the anti-HIV agent 9-(2-phosphonyl-methoxyethyl)-2,6-diaminopurine against cytomegalovirus in vitro and in vivo [published correction appears in Eur J Clin Microbiol Infect Dis 1993 Jul;12(7):following 477]. Eur J Clin Microbiol Infect Dis. 1993;12(6):437-446. [2]. Naesens L, et al. 9-(2-Phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP): a novel agent with anti-human immunodeficiency virus activity in vitro and potent anti-Moloney murine sarcoma virus activity in vivo. Eur J Clin Microbiol Infect Dis. 1989;8(12):1043-1047.
| Cas No. | 113852-41-8 | SDF | |
| 分子式 | C8H13N6O4P | 分子量 | 288.2 |
| 溶解度 | 0.1 M NaOH : 14.29 mg/mL (49.58 mM; ultrasonic and adjust pH to 12 with NaOH) | 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 | 3.4698 mL | 17.3491 mL | 34.6981 mL |
| 5 mM | 0.694 mL | 3.4698 mL | 6.9396 mL |
| 10 mM | 0.347 mL | 1.7349 mL | 3.4698 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。
N6-cyclopropyl-PMEDAP: a novel derivative of 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) with distinct metabolic, antiproliferative, and differentiation-inducing properties
Biochem Pharmacol 1999 Jul 15;58(2):311-23.PMID:10423173DOI:10.1016/s0006-2952(99)00091-x.
N6-Cyclopropyl-PMEDAP (cPr-PMEDAP) is a novel derivative of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP). Its cytostatic activity was found to be 8- to 20-fold more pronounced than that of PMEDAP and equivalent to that of the guanine derivative 9-(2-phosphonylmethoxyethyl)guanine (PMEG) against a variety of tumor cell lines. Unlike PMEDAP, but like PMEG, cPr-PMEDAP was equally cytostatic to wild-type and 9-(2-phosphonylmethoxyethyl)adenine/PMEDAP-resistant variants of the human erythroleukemia K562 and the murine leukemia L1210 cell lines. Also, cPr-PMEDAP and PMEG proved to be equipotent inducers of K562 and rat choriocarcinoma RCHO cell differentiation, whereas the differentiation-inducing activity of PMEDAP was 5- to 25-fold less pronounced. Furthermore, compared to PMEDAP, cPr-PMEDAP and PMEG were 10- to 25-fold more potent in inhibiting the progression of K562 cells through the S phase of the cell cycle, resulting in a marked accumulation of the four 2'-deoxyribonucleoside 5'-triphosphate pools. The biological effects of cPr-PMEDAP, but not PMEDAP, were reversed by the adenylate deaminase inhibitor 2'-deoxycoformycin (dCF). Formation of the deaminated derivative of cPr-PMEDAP (i.e. PMEG) was demonstrated in crude extracts from K562 and L1210 cells and in metabolism studies with radiolabeled cPr-PMEDAP and PMEG. This is the very first example of an acyclic nucleoside phosphonate analogue that is susceptible to deamination. However, cPr-PMEDAP was not recognized as a substrate by purified adenosine deaminase or by adenylate deaminase. These findings might point to an as yet unidentified cellular enzyme, sensitive to dCF but different from the common adenosine and AMP deaminases. Our data demonstrate the superior antiproliferative and differentiation-inducing effects of cPr-PMEDAP on tumor cells, as compared to the parent compound PMEDAP, based on the unique metabolic properties of this novel compound.
PMEDAP and its N6-substituted derivatives: genotoxic effect and apoptosis in in vitro conditions
Anticancer Res 2003 Nov-Dec;23(6C):4933-9.PMID:14981948doi
Genotoxic properties expressed as acquired chromosomal aberrations and induction of apoptosis after treatment with acyclic nucleoside phosphonates PMEG, PMEDAP and its N6-substituted derivatives Me2NEt-PMEDAP, allyl-PMEDAP, Me2-PMEDAP and cypr-PMEDAP, were studied in in vitro conditions. The genotoxic and antiproliferative effect of compounds was investigated on CCRF-CEM, HeLa S3, MRC-5 and Reh cell lines. PMEG and cypr-PMEDAP exhibit high genotoxic and cytostatic effect. PMEDAP and its N6-substituted derivatives Me2NEt-PMEDAP, allyl-PMEDAP and Me2-PMEDAP are considerably less genotoxic. Time- and dose-dependent suppression of proliferation by these nucleotide analogues is accompanied by induction of apoptosis, which is dependent on cell line type. However, an increased proliferation was observed after treatment of the cell culture with very low dose of PMEDAP. The sensitivity of cell lines to PMEDAP decreased in the order: CCRF-CEM > Reh > HeLa > MRC-5. The potential embryotoxic or teratogenic effect of PMEDAP and cypr-PMEDAP was examined in inbred rats involving the mutant allele Lx that determines the polydactyly-luxate syndrome. While the prevalent effect of cypr-PMEDAP during fetus development is embryolethality, PMEDAP did not induce any embryo-lethal or teratogenic effect.
Enhanced topical and transdermal delivery of antineoplastic and antiviral acyclic nucleoside phosphonate cPr-PMEDAP
Pharm Res 2011 Dec;28(12):3105-15.PMID:21671133DOI:10.1007/s11095-011-0508-4.
Purpose: Acyclic nucleoside phosphonates possess unique antiviral and antineoplastic activities; however, their polar phosphonate moiety is associated with low ability to cross biological membranes. We explored the potential of transdermal and topical delivery of 2,6-diaminopurine derivative cPr-PMEDAP. Methods: In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin. Results: Ability of 0.1-5% cPr-PMEDAP to cross human skin barrier was very low with flux values ~40 ng/cm(2)/h, the majority of compound found in the stratum corneum. The highest permeation rates were found at pH 6; increased donor concentration had no influence. The permeation enhancer dodecyl 6-dimethylaminohexanoate (DDAK, 1%) increased flux of cPr-PMEDAP (up to 61 times) and its concentration in nucleated epidermis (up to ~0.5 mg of cPr-PMEDAP/g of the tissue). No deamination of cPr-PMEDAP into PMEG occurred during permeation studies, but N-dealkylation into PMEDAP mediated by skin microflora was observed. Conclusions: Transdermal or topical application of cPr-PMEDAP enabled by the permeation enhancer DDAK may provide an attractive alternative route of administration of this potent antitumor and antiviral compound.
Experimental therapy with 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP): origin of resistance
Folia Biol (Praha) 2007;53(3):79-84.PMID:17579998doi
The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was studied in vitro (CCRF-CEM cells) and in vivo (spontaneous transplantable T-cell lymphoma of SD/Cub inbred rats). The increased resistance against the cytostatic agent PMEDAP during longterm treatment was found to be associated with overexpression of MRP4 and MRP5 genes. The course of both gene activation differs significantly. While the MRP5 function is important in the onset of PMEDAP resistance, the intensity of the relative MRP4 gene expression increases rather continuously. Our data indicate cooperative acting of both MRP4 and MRP5 genes during the PMEDAP resistance development.
Antitumour activity of N6-substituted PMEDAP derivatives against T-cell lymphoma
Anticancer Res 2001 May-Jun;21(3B):2057-64.PMID:11497298doi
The antitumour activity of four N6-substituted PMEDAP derivatives, Me2NEt-PMEDAP, allyl-PMEDAP, Me2-PMEDAP and cypr-PMEDAP, selected on the basis of their in vitro cytostatic activity, was studied in an in vivo model of haematological malignancy of inbred Sprague-Dawley rats. These compounds are believed to serve as the prodrugs of another (phosphonomethoxy)ethyl derivative, PMEG (9-[2-phosphonomethoxy) ethyl] guanine. We compared their toxicity and ability to inhibit tumour development in two different dosage regimes with those of their parent compound PMEDAP, as well with PMEG. The study confirmed the anticancer efficacy of the parental compound PMEDAP. Unlike PMEDAP, its N6-mono- and disubstituted congeners Me2NEt-PMEDAP, allyl-PMEDAP and Me2-PMEDAP were less potent or exhibited the same antineoplastic effect as PMEDAP. cypr-PMEDAP significantly decreased the survival of lymphoma-bearing rats due to high toxicity, which was approximately the same as that of PMEG. Therefore, these acyclic nucleoside phosphonates substituted at the 6-position of 2,6-diaminopurine ring do not seem to be promising drugs for the treatment of haematological malignancies.