Design, synthesis and Evaluation of Novel Small Molecule Modulators of Cell Signalling in Cancer

不受调节的细胞信号传导导致不受控制的细胞增殖，并构成癌症的标志。在这种情况下，细胞信号传导的小分子调节剂继续在抗癌药物发现中发挥主导作用。Baud小组专注于在癌症进展中发挥关键作用的几个重要信号通路，包括p53和Wnt信号通路。这些途径在正常的生物体发育中起着关键作用。然而，其活性的失调是几种癌症的标志，包括结直肠癌（CRC），这是世界上最致命的癌症之一。我们的目标是开发这些途径的新型小分子调节剂，作为原理验证的先导化合物，用于治疗癌症的一流疗法。主要目标是开发一个备受瞩目的药物发现项目，旨在确定新的抗癌小分子，靶向和调节这些途径的关键失调蛋白的生物活性。这将涉及合成小分子的分子设计、化学合成和生物物理/生物学评价。该项目的多学科性质将提供机会，以获得知识和技能，在其他相关学科都在我们的小组和我们的合作者。这些技术包括生物物理技术（例如DSF、NMR、ITC、FP、SPR、MST）、生物化学（例如蛋白质表达/纯化）、计算方法（例如对接）、细胞生物学（例如细胞毒性测定、蛋白质印迹）和结构技术（例如X射线晶体学）。

Unregulated cell signalling results in uncontrolled cell proliferation, and constitutes a hallmark of cancer. In this context, small molecule modulators of cell signalling continue to play a preponderant part in anticancer drug discovery. The Baud group group focuses on several important signalling pathways playing key roles in cancer progression, including the p53 and Wnt signalling pathways. These pathways play a pivotal role in normal organismal development. However, misregulation of their activity is a hallmark of several cancers, including colorectal cancer (CRC), one of the deadliest cancers worldwide. We aim to develop novel classes of small molecule modulators of these pathways, as proof-of-principle lead compounds towards first-in-class therapeutics against cancer.The primary objective will be to develop a high profile drug discovery project aimed at identifying new anticancer small molecules targeting and modulating the biological activity of key misregulated proteins of these pathways. This will involve the molecular design, chemical synthesis and biophysical/biological evaluation of the synthesised small molecules. The multidisciplinary nature of this project will provide the opportunity to acquire knowledge and skills in other relevant disciplines both in our group and with our collaborators. Those include biophysical techniques (e.g. DSF, NMR, ITC, FP, SPR, MST), biochemistry (e.g. protein expression/purification), computational approaches (e.g. docking), cell biology (e.g. cytotoxicity assays, Western-blots) and structural techniques (e.g. X-ray crystallography).