Fomivirsen
(Synonyms: ISIS-2922 free base) 目录号 : GC67756Fomivirsen (ISIS-2922 free base) 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 (cytomegalovirus retinitis (CMV)) 研究的抗病毒试剂。Fomivirsen 结合并降解 CMV immediate-early 2 蛋白的 mRNA，从而抑制病毒增殖。
Cas No.:144245-52-3
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 (ISIS-2922 free base) is an antisense 21 mer phosphorothioate oligonucleotide. Fomivirsen is an antiviral agent that is used cytomegalovirus retinitis (CMV) research, incluiding in AIDs. Fomivirsen binds to and degrades the mRNAs encoding CMV immediate-early 2 protein, thus inhibiting virus proliferation[1][2].
[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. | 144245-52-3 | SDF | Download SDF |
| 别名 | ISIS-2922 free base | ||
| 分子式 | C204H263N63O114P20S20 | 分子量 | 6682.4 |
| 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。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.1496 mL | 0.7482 mL | 1.4965 mL |
| 5 mM | 0.0299 mL | 0.1496 mL | 0.2993 mL |
| 10 mM | 0.015 mL | 0.0748 mL | 0.1496 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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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
Drugs 1999 Mar;57(3):375-80; discussion 381.PMID:10193689DOI:10.2165/00003495-199957030-00010.
Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically inhibits replication of human cytomegalovirus. It achieves this by binding to complementary sequences on messenger RNA transcribed from the major immediate-early transcriptional unit of the virus. It is being developed for the treatment of cytomegalovirus retinitis. Mean maximum retinal concentrations of Fomivirsen occurred approximately 2 days after a single intravitreal injection in monkeys. The elimination half-life of Fomivirsen (after a single 115 microg dose) in monkey retina was 78 hours. Fomivirsen, administered as an intravitreal injection, significantly delayed progression of cytomegalovirus retinitis in patients with AIDS in preliminary clinical trials. In 18 patients with newly diagnosed, unilateral, peripheral cytomegalovirus retinitis treated with Fomivirsen 165 microg once weekly for 3 weeks, then 165 microg every second week, the median time to disease progression was significantly longer than in 10 patients in whom Fomivirsen treatment was deferred until early disease progression (71 vs 14 days). In patients with advanced, refractory, sight-threatening disease, treatment with Fomivirsen 330 microg once weekly for 3 weeks and then 330 microg every 2 weeks (n = 34) or 330 microg on days 1 and 15 and then monthly (n = 20) significantly delayed disease progression. The interpolated median time to disease progression was 90 days in both treatment groups. The most common adverse events reported in clinical trials of Fomivirsen were increased intraocular pressure and mild to moderate intraocular inflammation. These events were generally transient or reversible with topical steroid treatment.
Fomivirsen
Drugs Today (Barc) 2001 Apr;37(4):245-255.PMID:12768225DOI:10.1358/dot.2001.37.4.620590.
Cytomegalovirus (CMV) retinitis can rapidly lead to blindness in patients with acquired immune deficiency syndrome (AIDS). Fomivirsen is a novel antisense drug with a 21-nucleotide sequence complementary to the immediate early region 2 of CMV messenger ribonucleic acid. In clinical trials, Fomivirsen was shown to provide effective treatment for newly diagnosed, peripheral CMV retinitis in patients with AIDS and in those with relapsed CMV retinitis that is unresponsive to conventional therapy. These trials also demonstrated that local treatment with Fomivirsen does not result in measurable systemic absorption of Fomivirsen or its metabolites. Thus, there is minimal risk of systemic exposure to Fomivirsen or its metabolites with intravitreal dosing at either 165 mcg or 330 mcg. The only clinically relevant adverse events are mild to moderate local ocular effects that are transient and manageable with topical medications. (c) 2001 Prous Science. All rights reserved.
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.
Fomivirsen - a phosphorothioate oligonucleotide for the treatment of CMV retinitis
Ocul Immunol Inflamm 1999 Dec;7(3-4):189-98.PMID:10611727DOI:10.1076/ocii.7.3.189.4007.
Fomivirsen is a 21-nucleotide phosphorothioate oligonucleotide which, when injected into a human eye, is capable of inhibiting CMV retinitis. Its mode of action is consistent with an antisense mechanism. Prior to human trials, Fomivirsen was tested in a number of in vitro cell lines and was found to inhibit CMV replication in a dose-dependent manner with a mean 50% inhibitory concentration between 0.03 and 0.2 microM. Intravitreal drug clearance studies have revealed first-order kinetics with a half-life in the rabbit of 62 hours. In a clinical trial of patients with newly diagnosed CMV retinitis receiving 165 mg per injection, time to progression was interpolated to 71 days with 44% of the patients remaining on treatment for over one year. In patients who failed other anti-CMV treatments, the interpolated time to progression was 91 days when receiving 330 mg per injection. No systemic absorption of the drug could be detected. Reported adverse events have been for the most part mild to moderate in intensity and either resolved spontaneously or were treatable with topical medications. Locally administered Fomivirsen effectively inhibits CMV retinitis using a mode of action which is complementary to existing DNA polymerase inhibitors.
Adverse Drug Reactions and Toxicity of the Food and Drug Administration-Approved Antisense Oligonucleotide Drugs
Drug Metab Dispos 2022 Jun;50(6):879-887.PMID:35221289DOI:10.1124/dmd.121.000418.
The market for large molecule biologic drugs has grown rapidly, including antisense oligonucleotide (ASO) drugs. ASO drugs work as single-stranded synthetic oligonucleotides that reduce production or alter functions of disease-causing proteins through various mechanisms, such as mRNA degradation, exon skipping, and ASO-protein interactions. Since the first ASO drug, Fomivirsen, was approved in 1998, the U.S. Food and Drug Administration (FDA) has approved 10 ASO drugs to date. Although ASO drugs are efficacious in treating some diseases that are untargetable by small-molecule chemical drugs, concerns on adverse drug reactions (ADRs) and toxicity cannot be ignored. Illustrative of this, mipomersen was recently taken off the market due to its hepatotoxicity risk. This paper reviews ADRs and toxicity from FDA drug labeling, preclinical studies, clinical trials, and postmarketing real-world studies on the 10 FDA-approved ASO drugs, including Fomivirsen and pegaptanib, mipomersen, nusinersen, inotersen, defibrotide, eteplirsen, golodirsen, viltolarsen, and casimersen. Unique and common ADRs and toxicity for each ASO drug are summarized here. The risk of developing hepatotoxicity, kidney toxicity, and hypersensitivity reactions co-exists for multiple ASO drugs. Special precautions need to be in place when certain ASO drugs are administrated. Further discussion is extended on studying the mechanisms of ADRs and toxicity of these drugs, evaluating the existing physiologic and pathologic states of patients, optimizing the dose and route of administration, and formulating personalized treatment plans to improve the clinical utility of FDA-approved ASO drugs and discovery and development of new ASO drugs with reduced ADRs. SIGNIFICANCE STATEMENT: The current review provides a comprehensive analysis of unique and common ADRs and the toxicity of FDA-approved ASO drugs. The information can help better manage the risk of severe hepatotoxicity, kidney toxicity, and hypersensitivity reactions in the usage of currently approved ASO drugs and the discovery and development of new and safer ASO drugs.