每周分子Molecule of the Week
Molecule of the Week: Sofosbuvir
每周分子：索非布韦
丙型肝炎是一种传播速度非常快的疾病，人类仍在寻找一种适用于所有丙型肝炎的药物。目前，利用抗病毒组合物（大多名称以“vir”结尾）组成的药物混合物来治疗每一种丙肝病毒。
索非布韦就是这样的一种化合物。2007年，Michael Sofia在Pharmasset（现在是吉利德科技公司的一部分）发现了索非布韦。2013年，FDA批准在美国使用索非布韦。FDA批准的是索非布韦和利巴韦林（一种可以追溯到1972年的抗病毒药物）联合使用。索非布韦是吉利德（Gilead）的产品Sovaldi和harvard oni的活性成分，你可能在电视上看到过其广告。
索非布韦是吉利德和制药巨头默克公司间备受关注的专利诉讼主体。默克声称索非布韦模仿了默克公司收购的Idenix制药公司的专利。经过一系列的审判后，联邦陪审团裁定因为吉利德侵犯了Idenix的专利，吉利德向默克公司支付25.4亿美元（没错，是几十亿美元）。
吉利德上诉；今年2月，美国一家地方法院的法官推翻了此前的裁决，称Idenix的专利过于宽泛，即便是熟练的化学家也不可能从这篇专利的信息中轻易获得索非布韦。法官据此判定该专利无效。默克公司誓言要上诉推翻这项裁决。
索非布韦危害信息
| GHS 分类*：皮肤刺激性，分类2 | |
| H315—致皮肤刺激 | |
| GHS 分类：皮肤致敏性，分类1 | |
| H317—可致过敏性皮肤反应 | |
| GHS 分类：严重眼损伤，分类1 | |
| H318—致严重的眼损伤 | |
| GHS 分类：呼吸道过敏，分类1 | |
| H334—吸入可致过敏或哮喘症状或呼吸困难 | |
| GHS 分类：特定目标器官毒性，单次曝露，呼吸道刺激，分类3 | |
| H335—可引起呼吸道刺激 | |
| GHS 分类：生殖细胞致突变物质，分类2 | |
| H341—疑致遗传缺陷 | |
| GHS 分类：生殖毒性，分类2 | |
| H361—疑损害生育能力或胎儿 | |
| GHS 分类：特定目标器官毒性，单次曝露，分类1 | |
| H370—对器官造成损害 | |
| GHS 分类：危害水生环境，长期危害，分类4 | |
| H413—可对水生生物造成长期不良影响 |
索非布韦信息速览
| CAS 登记号 | 1190307-88-0 |
| 摩尔质量 | 529.46 g/mol |
| 分子式 | C22H29FN3O9P |
| 外观 | 白色到米黄色的晶体或粉末 |
| 熔点 | 94–125 ºC* |
| 水溶性 | ≈105 mg/L* |
*依晶型决定.
【关于每周分子 】
自2001年以来，“每周分子”已成为广受欢迎的栏目。多数分子由读者推荐。每个结构都经由科学家审查，并以3-D和平面图像的形式显示，同时附有该分子简介。可以通过美国化学文摘社（CAS）提供的SciFinder中的CAS REGISTRY获取每周分子的更多信息。CAS REGISTRY中的每条物质信息都展示了物质的CAS登记号、索引名、通用名、商品名、书目信息等其他更多信息。发送邮件至motw@acs.org推荐您感兴趣的分子。
Hepatitis C is a burgeoning disease that is still in search of a one-drug-fits-all solution. Currently, each hepatitis C virus genotype is treated with a pharmaceutical cocktail that consists of a mixture of antivirals, most of whose names end with “vir”.
Sofosbuvir is one such compound. It was discovered in 2007 by Michael Sofia at Pharmasset (now part of Gilead Sciences) and approved for use in the United States by the Food and Drug Administration in 2013. The FDA approval was for the combination of sofosbuvir and ribavirin, an antiviral that dates back to 1972. Sofosbuvir is the active ingredient in Gilead’s products Sovaldi and Harvoni, ads for which you may have seen on TV.
Sofosbuvir was the subject of a high-profile patent lawsuit involving Gilead and drug giant Merck. Merck contended that sofosbuvir was patterned after a patent awarded to Idenix Pharmaceuticals, a company that Merck had acquired. After a series of trials, a federal jury ordered Gilead to pay Merck US$2.54 billion (that’s right, billion) for infringing the Idenix patent.
Gilead appealed; and this past February, the judge in a US district court overturned the award, writing that the Idenix patent was too broad and that a skilled chemist could not easily derive sofosbuvir from the information in the patent. For the same reason, the judge invalidated the patent.
Merck has vowed to appeal the overturn ruling.
Sofosbuvir fast facts
| CAS Reg. No. | 1190307-88-0 |
| Molar mass | 529.46 g/mol |
| Empirical formula | C22H29FN3O9P |
| Appearance | White to off-white crystals or powder |
| Melting point | 94–125 ºC* |
| Water solubility | ≈105 mg/L* |
*Depends on crystalline polymorph.
Sofosbuvir hazard information
| GHS classification**: skin irritation, category 2 | |
| H315—Causes skin irritation | |
| GHS classification: skin sensitization, category 1 | |
| H317—May cause an allergic skin reaction | |
| GHS classification: serious eye damage, category 1 | |
| H318—Causes serious eye damage | |
| GHS classification: respiratory sensitisation, category 1 | |
| H334—May cause allergy or asthma symptoms or breathing difficulties if inhaled | |
| GHS classification: specific target organ toxicity, single exposure, respiratory tract irritation, category3 | |
| H335—May cause respiratory irritation | |
| GHS classification: germ cell mutagenicity, category 2 | |
| H341—Suspected of causing genetic defects | |
| GHS classification: reproductive toxicity, category 2 | |
| H361—Suspected of damaging fertility or the unborn child | |
| GHS classification: specific target organ toxicity, single exposure, category 1 | |
| H370—Causes damage to organs | |
| GHS classification: hazardous to the aquatic environment, long-term hazard, category 4 | |
| H413—May cause long-lasting harmful effects to aquatic life |
**Globally Harmonized System of Classification and Labeling of Chemicals. Explanation of pictograms.
About Molecule of the Week
MOTW has been a popular feature on ACS website since 2001. Many molecules are suggested by our website visitors. Every structure is reviewed by a scientist and displayed in 3-D and flat images with a brief description. Each week’s molecule also links to a sample record from the CAS REGISTRY, which is searched using SciFinder. Each record displays the registry number, index name and synonyms, bibliographic information, and more. Send us a molecule suggestion at motw@acs.org.
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