辉瑞利用基于模型的药物开发来帮助减少II期磨损率

挑战

Reduce phase II attrition in clinical drug trials

结果

深化药物互动的洞察
Costly laboratory resource spending and clinical trials avoided
研究生产力增加

“Pfizer is integrating modeling, simulation, and statistical analysis throughout drug discovery and development. This approach helps reduce phase II attrition by guiding the selection of the best biological pathway, target, molecule, dosing regimen, and patient population.”
Piet Van der Graaf博士，辉瑞

Example pathway model (top) and drug response simulation (bottom).

By the time a new drug reaches phase II clinical trials, the pharmaceutical company has invested millions of dollars and years of research and development. If late-stage trials show that the drug is insufficiently effective or causes unacceptable side effects, much of that investment is wasted. This第二阶段磨擦poses serious challenges for pharmaceutical companies, not only for financial reasons, but also because it drains development resources away from successful new treatments.

辉瑞研究人员使用Matlab等计算工具^®和偶像^®支持基金宝app于模型的药物开发，帮助减少II期磨损。“发表的生物学研究的日益增长的数据库提供了弥补人体的巨大复杂系统的快照，”辉瑞的药代动力学，动态和新陈代谢（PDM）助理研究员们·尼尔本森博士说。“辛博学使我们能够根据可用的研究数据构建生物系统的复杂模型。通过模拟这些系统，我们可以更好地了解他们的动力学和动态，然后使用这种理解将我们的研究集中在最有前途的生物学目标上。“

挑战

辉瑞公司致力于模型的药物开发。“在早期发现中选择生物目标的根本原因，需要在根本原因中解决第二阶段，”Piet Van der Graaf，Piet Van der Graaf，Piet Van der Graf，PermicateRics，临床药理学博士说。“我们希望在早期的药物研究阶段应用建模和仿真，并弥合系统生物学和药代动力学 - 药学动力学（PK / PD）建模方法之间的差距。”

基于文本的界面的建模软件e packages can make it difficult to construct and share increasingly sophisticated models. “We had to write all the equations by hand. As our models got bigger, there were many more equations to type in, and constructing them and ensuring consistency of the units became very laborious,” says Benson. “In addition, when we needed to communicate our work with other researchers, the long list of equations was not easy for them to understand, particularly if they were not expert modelers.”

Projects typically require significant preclinical laboratory investment to build confidence in an approach and subsequent clinical trials to validate hypotheses. To avoid spending millions of dollars and years of research effort on projects or approaches that cannot succeed, Pfizer wanted to be able to identify and terminate them earlier.

解决方案

辉瑞公司已开始开发一体化系统药理学研究人员使用诸如Matlab和Simbiology等工具的方法，以在发现和整个开发的最早阶段模拟，模拟和分析生物系统。

Researchers construct Systems Pharmacology models to answer questions about a given pathway, such as which receptors are likely to be the best targets and what concentration of drug compound is needed to achieve the required inhibition.

有时，该组基于发布的系统生物学标记语言（SBML）模型的初始模型，直接导入SimBiology和其他软件工具。

他们接下来对模型中的模拟事件进行识别和排列模型中最重要的目标的敏感性分析，以模拟特定药物进入系统。

They visualize results by reviewing diagnostic plots, including time course plots with and without the drug present.

使用视觉接口，它们与项目团队共享模型，绘图和其他模拟结果，用于提供参数估计或其他输入以进一步完善模型。

在一个项目中，该团队探讨了使用小干扰RNA（siRNA）抑制NF-KB途径中IKK酶的有效性。在构建和模拟具有26种和64个参数的模型之后，他们发现所提供的抑制siRNA水平不足以达到所需的结果。随后的实验结果与此结论一致。

Pfizer is currently assembling a library of Systems Pharmacology model components that can be reused for different projects to further accelerate analysis using PK and systems biology models.

结果

深化药物互动的洞察。“我不是数学家，但是用偶像学，我构建了多达400个常微分方程的模型，”Benson说。“辛生物学让我创造比以前更复杂的型号，并提供了深入了解如何通过能够分析其动力学和动态来实现他们的工作。”

Costly laboratory resource spending and clinical trials avoided。“On multiple projects, including the one focused on siRNA and the NF-kB pathway, results from Systems Pharmacology have demonstrated that a particular drug would not work and ultimately the data generated were consistent with this,” notes Benson. “In the case of the siRNA project, the modeling could have been carried out prior to engaging any laboratory resource.”

研究生产力增加。“During drug discovery, lots of experiments can be performed,” notes Benson. “We use Systems Pharmacology results to focus these efforts and propose optimal experiments. We can narrow the experiments we perform, focusing on the most promising biological targets.”

下载188bet金宝搏使用的产品

了解有关PFizer Inc.的更多信息

Comparte tu éxito

Únete al Customer Reference Program

Get started