Medicinal chemistry core

核心3：药物化学 摘要 尽管已经开发出有效的疫苗来应对新冠肺炎大流行，但重大挑战 与它们在全球范围内的分发和管理有关，并与疫苗问题相结合 犹豫不决，使人们关注到同样迫切需要安全有效的抗病毒疗法。一位现成的 分散的、口服生物可用的小分子抗病毒药物可能在持续的 通过降低新冠肺炎高危人群的疾病严重程度来应对新冠肺炎和未来的大流行 严重后果，从而减少严重疾病给医院和医疗保健带来的压力 基础设施。药物化学核心在更大的QCRG大流行应对计划中的作用 是使项目团队能够将他们对特定病毒家族和蛋白质靶标的专业知识 我们的行业合作伙伴罗氏可以迅速开发成有效的新抗病毒药物 治疗。药物发现是一项高度合作的事业，需要不同的科学和技术专长， 这反映在作为QCRG大流行应对计划一部分的项目和核心中 (见图1)。将一种有效的筛选“成功”转化为药物先导，需要一个化合物设计的迭代过程 以及化学合成，其特征不仅是优化配体-目标结合，而且同样 重要的是，通过优化体内的类似药物的性质，确保分子将在 并提供一种产生临床疗效的持续抑制作用。药物化学核心 将利用其核心领导Renslo博士和Co-is金博士和Dr。 Shoichet，项目和核心的专业知识，以及可在CRO获得的ADME和PK/Tox分析，以转换 根据我们针对抗病毒药物的目标产品简介(TPP)，按照此途径验证对优化销售线索的命中率 小分子疗法。然后，这些优化的线索将被转移到我们的行业合作伙伴罗氏 进一步的临床前和临床发展。

CORE 3: MEDICINAL CHEMISTRY SUMMARY Despite the development of effective vaccines to address the COVID-19 pandemic, the significant challenges associated with their distribution and administration on a global scale, combined with the issue of vaccine hesitancy, has put a spotlight on the equally urgent need for safe and effective antiviral therapeutics. A readily distributed, orally bioavailable small molecule antiviral agent could play an outsized role in the continuing response to COVID-19 and in future pandemics by reducing the severity of disease for those at highest risk for serious outcomes and thereby curtailing the strain that serious illness puts on hospitals and healthcare infrastructure. The role of the Medicinal Chemistry Core in the larger QCRG Pandemic Response Program is to enable the Project teams to translate their expert knowledge of specific viral families and protein targets into small molecule drug leads that our industry partner Roche could rapidly develop into effective new antiviral therapies. Drug discovery is a highly collaborative enterprise requiring diverse scientific and technical expertise, and this is reflected in the Projects and Cores assembled as part of the QCRG Pandemic Response Program (see Fig. 1). Turning a validated screening ‘hit’ into a drug lead involves an iterative process of compound design and chemical synthesis that is characterized not only by optimization of ligand–target binding, but equally importantly by the optimization of in vivo ‘drug-like’ properties to ensure the molecule will reach its target in an animal and provide a sustained inhibitory effect that produces clinical efficacy. The Medicinal Chemistry Core will leverage the decades of drug discovery experience of its Core Lead Dr. Renslo and Co-Is Dr. Jin and Dr. Shoichet, the expertise of the Projects and Cores, and ADME and PK/Tox assays available at CROs, to convert validated hits into Optimized Leads, guided along this path by our Target Product Profile (TPP) for an antiviral small molecule therapeutics. These Optimized Leads will then be transferred to our industry partner Roche for further pre-clinical and clinical development.