媒体声音 | 从「做实验」到「做决策」：一体化平台如何重塑早期新药研发 | Bilingual

在近期结束的美国癌症研究协会（AACR）年会上，全球目光聚焦于癌症科学的快速演进：新靶点不断涌现，生物学认知持续深化，治疗策略也加速迭代。然而，真正决定这些突破能否走向患者的关键，在于如何将前沿科学高效转化为具备开发潜力的候选药物。

为了帮助全球创新者更好地应对这一挑战，药明康德依托独特的一体化CRDMO平台，将研究、开发与生产能力整合在一个全球化的体系之中，助力合作伙伴优化研发流程、提升项目效率。凭借二十余年的行业积累，药明康德持续支持客户加快项目推进，推动创新疗法更早惠及患者。

借AACR大会这一契机，药明康德研发化学服务部业务拓展与一体化项目管理负责人郭涛博士接受行业媒体GEN采访，剖析当前药物发现领域的重要趋势，并介绍一体化平台如何高效赋能早期研发，造福病患。

以下为采访全文，点击“阅读原文/Read More”即可访问原文页面。

GEN：感谢您接受我们的采访。今年AACR年会带来了很多新的研究进展。在新药发现领域，您认为有哪些关键趋势值得关注？

郭涛博士：目前有三个方向特别值得留意。首先，靶向蛋白降解（TPD）领域正在不断拓展。原先大家一说到E3连接酶，就会想到传统的CRBN和VHL。但现在，DCAF15和KEAP1等全新的E3连接酶得到了越来越多的关注。其次，我们也看到了更多的合成致死策略。以前这一领域主要是PARP抑制剂。如今，PRMT5和WRN等靶点也展现出了更广阔的发展潜力。第三，偶联药物发展迅速。一方面，抗体偶联药物（ADC）出现了更多创新的载荷和连接子技术。同时，降解剂-抗体偶联物（DAC）等融合不同治疗模式的新兴方向也正在涌现。

这些科学进展对早期研发思路带来了明显的变化。目前，新药研发团队已不再局限于单一靶点，而是更多从整体信号通路层面开展研究，比如MAPK或PI3K等通路就是目前的一些研发重点。此外，早期研发也应该提前考虑由肿瘤生物学驱动的适应性耐药机制。

与此同时，衡量早期研发是否成功的标准也在变化。化合物的活性固然重要，但与靶点结合的动力学特征、靶点占据持续时间，以及能否在早期将生物标志物加入到评估体系，正被越来越多人纳入考量，也成为了提升临床转化成功率的重要因素。

图片来源：123RF

GEN：在这些变化之下，药物发现化学在新药研发中的角色，有没有发生相应的转变呢？

郭涛博士：药物发现化学已不再是过去相对线性、“被动响应”的角色。相反，它已经以更加一体化、深度协同的方式，参与到新药研发之中。

比如现在，药物化学家越来越早地参与到项目中来，在早期就与生物学家一起推进靶点假设、机制验证以及实验设计。同时，随着计算工具和一体化数据体系的应用，研发模式也从过去被动的“按需合成”，逐步转向更加主动的“预测驱动设计”。

在药明康德，我们推出了名为“Direct-to-Biology”的一体化工作平台。通过化学合成与生物活性测定之间更紧密、实时的联动，这个平台可以显著提升“设计—合成—测试—分析”这一早期研发循环的效率。

换句话说，时至今日，药物发现化学与生物学早已不再是彼此独立的环节，而是围绕关键决策与项目结果，不断迭代、协同推进的一个一体化过程。

GEN：从推进早期研发项目，最终造福病患的角度看，您认为产业目前还面临哪些关键挑战？药明康德通常是如何应对这些问题的？

郭涛博士：目前来看，核心挑战之一仍然是研发成果的可转化性。我们经常会看到，一些在体外实验中表现非常优异的化合物，进入细胞或动物体内之后，往往难以复制同样的效果。这种情况在降解剂或ADC等复杂分子类型中更加明显。与此同时，随着检测体系越来越复杂，如何高效解析大规模的数据，也逐渐成为新的挑战。

针对这些问题，药明康德的做法是尽可能在药物发现早期，就把化学、生物学以及测试能力整合在一起。例如，构建更高质量的化合物库，在关注活性的同时推进多参数优化，并加快化合物系列的筛选与迭代。

通过实时的数据整合，以及高效的一体化工作流程，我们可以帮助客户在研发项目中，更早决定是继续推进，还是及时终止。这在降低后期研发风险的同时，也能提升整体的研发效率。

GEN：对于中小型生物技术公司来说，在早期研发阶段，您认为对它们帮助最大的是什么？

郭涛博士：很多中小型生物技术公司缺乏一体化的研发基础设施。其实，很多公司在生物学或分子设计方面是有优势的，但在化学能力、测试体系以及跨环节协同方面，往往还没有搭建起完整的体系，这在一定程度上会限制研发速度，也阻碍项目的规模化推进。

而一体化研发平台在这一阶段可以起到关键作用。通过与这些公司合作，可以发挥双方的所长——药明康德提供端到端支持，帮助客户更高效地推进项目，将概念转变为临床前候选化合物阶段；而客户团队则可以更加专注于科学创新。双方的合作可以加快整体执行落地的速度。

GEN：感谢您的洞见。展望未来，您认为药物发现化学还会呈现出哪些值得关注的发展趋势？

郭涛博士：从目前的发展趋势来看，药物发现化学的未来会突破单一治疗模式的限制，转而平行覆盖小分子、降解剂以及各类偶联分子等不同方向。与此同时，我们也看到像流动化学、高通量实验以及自动化等技术，正在不断拓展可探索的化学空间，并持续提升研发效率。

另外一个很重要的趋势是，药物发现与后续开发和生产阶段之间的协同会越来越紧密。在一体化CRDMO模式下，团队可以在分子设计的早期就考虑工艺可行性与放大生产等因素，从而减少不同研发阶段之间的衔接成本，加快项目推进。

总体来看，药物发现正从“以化合物为中心”逐步转向“以结果为导向”。在把科学创新高效转化为惠及患者的药物这一过程中，如何使用好一体化的能力平台，很可能会成为决定项目成败的关键因素。

How Integrating Chemistry and Biology Reshapes Early Drug Development

At the American Association for Cancer Research (AACR) Annual Meeting, the spotlight often reflects the rapid pace of cancer science: new targets, emerging biology, and evolving therapeutic approaches. But the real challenge lies in translating these scientific advances into viable drug candidates. Before this year’s meeting, GEN spoke with Tao Guo, Ph.D., Senior Vice President, Research Chemistry Services, Integrated Program Management at WuXi AppTec, about emerging trends and how integrated approaches are reshaping early discovery.

GEN: What stands out to you on the discovery side this year?

Tao Guo:Three areas stand out. First,targeted protein degradation (TPD) is expanding beyond traditional E3 ligaseslike CRBN and VHL into newer systems such as DCAF15 and KEAP1. Second,synthetic lethality continues to evolve beyond PARP inhibitors, with targets like PRMT5 and WRN showing broader potential. Third,antibody-drug conjugates (ADCs) are advancing rapidly, with innovations in payloads and linkers, as well as emerging approaches like degrader-antibody conjugates that combine modalities.

These scientific advances have also influenced early-stage discovery thinking. Instead of focusing on a single target, teams now consider entire pathways such as MAPK or PI3K and anticipate adaptive resistance mechanisms driven by tumor biology. At the same time, success is no longer defined by potency alone. There is greater emphasis on binding kinetics, target engagement duration, and early integration of biomarker strategies to improve clinical translation.

Image source：123RF

GEN: How has the role of discovery chemistry evolved to support these changes?

Tao Guo:Discovery chemistry has shifted from a linear, reactive role to a highly integrated one.Medicinal chemists are now involved from the beginning, working alongside biologists in target hypothesis, validation, and experimental design. We are also moving from reactive synthesis to predictive design, supported by computational tools and integrated datasets. “Direct-to-Biology” workflows enable faster design–make–test–analyze cycles, linking synthesis and biological testing in real time. As a result,chemistry and biology are no longer separate steps but part of a single, iterative process focused on decision-making and outcomes.

GEN: Do you still see any challenges? How is WuXi AppTec addressing them?

Tao Guo:A key challenge is translatability.Compounds that perform well in vitro often fail in cellular or in vivo systems, especially with complex modalities like degraders or ADC payloads. At the same time, increasing assay complexity generates large datasets that are difficult to interpret efficiently.

At WuXi AppTec, we address this by integrating chemistry, biology, and testing early in the discovery process. This includes designing higher-quality libraries, applying multi-parameter optimization beyond potency, and enabling rapid triage of chemical series. By combining real-time data integration with iterative workflows, we can enable our customers to make earlier, more informed go or no-go decisions, thereby reducing downstream risk and improving overall efficiency.

GEN: Where do smaller biotech companies face the biggest gaps in early discovery?

Tao Guo:The biggest gap is access to integrated infrastructure. Many smaller biotechs have strong biology or design expertise but lack capabilities in chemistry, testing, and coordinated workflows, which limit both speed and scale.

Integrated platforms can help bridge this gap. By providing end-to-end support, WuXi AppTec can help our customers’ programs move more efficiently from target concept to preclinical candidate, allowing smaller teams to focus on scientific direction while accelerating execution.

GEN: Looking ahead, what shifts do you expect in discovery chemistry?

Tao Guo:Discovery chemistry is becoming more modality-agnostic, spanning small molecules, degraders, and conjugates. New technologies such as flow chemistry, high-throughput experimentation, and automation are expanding access to novel chemical space and improving speed.

Equally important, discovery is becoming more closely aligned with development and manufacturing.Within an integrated CRDMO model, teams can incorporate considerations such as process feasibility and scalability earlier in design, reducing handoff friction and accelerating progression.

Overall, discovery is evolving from a compound-focused discipline to an outcome-focused one.Success increasingly depends on how well capabilities are integrated to translate scientific advances into medicines that can reach patients.

免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

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