Fomivirsen sodium
(Synonyms: ISIS-2922) 目录号 : GC64041
Fomivirsen sodium 是一种反义21 mer 磷酸硫寡核苷酸。Fomivirsen 是一种用于巨细胞病毒视网膜炎 (CMV) 研究的抗病毒试剂 ( antiviral agent)。Fomivirsen sodium 结合并降解 CMV immediate-early 2 蛋白(病毒复制所需) 的 mRNA，从而通过抑制病毒增殖。
Cas No.:160369-77-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fomivirsen sodium is an antisense 21 mer phosphorothioate oligonucleotide. Fomivirsen is an antiviral agent that is used cytomegalovirus retinitis (CMV) research, incluiding in AIDs. Fomivirsen sodium binds to and degrades the mRNAs encoding CMV immediate-early 2 protein (required for viral replication), thus providing bioactive effects for CMV retinitis by inhibition of virus proliferation[1].
Antisense oligonucleotide acts a complementary nucleotide to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, it disrupts the replication of the virus through an antisense mechanism[1].Fomivirsen is 21-mer phosphorothioate ASO with CpG motif near its 5′ end, with the sequence 5′-GCG TTT GCT CTT CTT CTT GCG-3′, resulting in mRNA degradation by RNase H-mediated mechanism[2].Fomivirsen inhibits CMV replication in human retinal pigment epithelial (RPE) cells and in human fibroblast cells (MRC-5 cells) in a dose-dependent manner. The mean IC50 are 0.03 µM for RPE cells and 0.2 µM for MRC5 cells[1].
[1]. M D de Smet, et al. Fomivirsen- a phosphorothioate oligonucleotide for the treatment of CMV retinitis. Ocul Immunol Inflamm. 1999 Dec;7(3-4):189-98.
[2]. Anna Kilanowska, et al. In vivo and in vitro studies of antisense oligonucleotides - a review. (Review Article) RSC Adv., 2020, 10, 34501-34516
| Cas No. | 160369-77-7 | SDF | Download SDF |
| 别名 | ISIS-2922 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 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。 | ||
| 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。
Fomivirsen: clinical pharmacology and potential drug interactions
Clin Pharmacokinet 2002;41(4):255-60.PMID:11978144DOI:10.2165/00003088-200241040-00002.
Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide complementary to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, and is a potent and selective antiviral agent for cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is slowly cleared from vitreous with a half-life of approximately 55 hours in humans. Preclinical studies show that fomivirsen distributes to retina and is slowly metabolised by exonuclease digestion. Clearance from retina was shown to be similarly slow following loading from the vitreous. The estimated half-life for clearance of fomivirsen from retina was 78 hours in monkeys following a 115-microg dose. Because of the low doses coupled with slow disposition from the eye, measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Systemically administered phosphorothioate oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in blood plasma. Because fomivirsen does not compete for oxidative metabolic processes involved in clearance of many xenobiotics, the most likely mechanism for drug interactions may be altered protein binding of a coadministered drug. The extremely low systemic exposure to this oligodeoxynucleotide following intravitreal administration largely negates its potential ability to interact with systemically administered drugs. Even if fomivirsen were able to access the blood, protein binding assays indicate that drugs that are site I and site II binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the presence of phosphorothioate oligodeoxynucleotides of various sequences at concentrations orders of magnitude higher than that seen for fomivirsen. Administration of fomivirsen with numerous systemically administered antiretrovirals (for example zidovudine and zalcitabine) as well as systemically administered anticytomegalovirus agents such as foscarnet and ganciclovir has been reported to be well tolerated. The only reported warning is a recommendation against administration within 2 to 4 weeks of cidofovir treatment due to an increased risk of ocular inflammation.
A randomized controlled clinical trial of intravitreous fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDS
Am J Ophthalmol 2002 Apr;133(4):467-74.PMID:11931780DOI:10.1016/s0002-9394(02)01327-2.
Purpose: To assess the efficacy of intravitreous Fomivirsen sodium, an antisense oligonucleotide, for newly diagnosed peripheral cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Design: Randomized treatment intervention clinical trial. Methods: A multicenter, prospective, and randomized clinical trial compared immediate treatment of CMV retinitis with fomivirsen (165 microg administered intravitreously) to deferral of treatment until CMV retinitis lesions progressed by standard definitions. Included were patients with CMV retinitis lesions at least 750 microm outside of zone 1. Fomivirsen was injected weekly for three doses as induction therapy, followed by injection every other week as maintenance therapy. All patients were examined regularly until evidence of retinitis progression. Time to first progression was determined by two independent masked fundus photography reading centers (principal outcome) and by clinician investigators based on indirect ophthalmoscopy. Patients in the deferral of treatment group were offered fomivirsen therapy at the time of clinically determined retinitis progression. Results: Patients in the immediate treatment group (n = 18) and the deferral of treatment group (n = 10) were comparable at baseline. Median time to first progression of disease for the immediate treatment group was 71 days (95% confidence interval [CI] 28 days-not determinable) and for the deferral of treatment group was 13 days (95% CI 9-15 days; P =.0001, Wilcoxon rank sum test). Progression occurred in 44% of patients in the immediate treatment group during the study compared with 70% of patients in the deferral of treatment group during the study. There were no retinal detachments among eyes treated with fomivirsen. Conclusions: Fomivirsen is an effective treatment for CMV retinitis in patients with AIDS that utilizes a mechanism of action different than that of ganciclovir, foscarnet, and cidofovir.
Evolving guidelines for intravitreous injections
Retina 2004 Oct;24(5 Suppl):S3-19.PMID:15483476DOI:10.1097/00006982-200410001-00002.
Intravitreous (i.v.t.) injection is increasingly being incorporated into the management of ocular diseases. While only Fomivirsen sodium (Vitravene) is currently approved by the Food and Drug Administration as an i.v.t. injection, the number of approved i.v.t. injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for i.v.t. injection. The purpose of this document is to identify specific strategies for the delivery of i.v.t. injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of i.v.t. injection, additional clinical experience, and results of clinical trials.