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

癌症细胞信号传导新型小分子调节剂的设计、合成和评估

基本信息

批准号：
1940843
负责人：
金额：
--
依托单位：
University of Southampton
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1940843
关键词：
Design synthesis Evaluation Novel Small

项目摘要

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).

不受调节的细胞信号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的发现中发挥着重要作用。Baud小组关注在癌症进展中起关键作用的几个重要信号通路，包括p53和Wnt信号通路。这些途径在正常的机体发育中起着关键作用。然而，它们的活动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，作为原理证明的先导化合物，用于抗癌的一流治疗。主要目标将是开发一个备受瞩目的药物发现项目，旨在识别新的抗癌小分子，靶向并调节这些途径中关键错误调节蛋白的生物活性。这将涉及分子设计，化学合成和合成小分子的生物物理/生物评价。这个项目的多学科性质将为我们小组和我们的合作者提供获得其他相关学科知识和技能的机会。这些技术包括生物物理技术（如DSF、NMR、ITC、FP、SPR、MST）、生物化学（如蛋白质表达/纯化）、计算方法（如对接）、细胞生物学（如细胞毒性测定、Western-blots）和结构技术（如x射线晶体学）。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Discovery of Nanomolar-Affinity Pharmacological Chaperones Stabilizing the Oncogenic p53 Mutant Y220C.

DOI：
10.1021/acsptsci.2c00164
发表时间：
2022-11-11
期刊：
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
影响因子：
0
作者：
Stephenson Clarke, Joseph R;Douglas, Leon R;Duriez, Patrick J;Balourdas, Dimitrios-Ilias;Joerger, Andreas C;Khadiullina, Raniya;Bulatov, Emil;Baud, Matthias G J
通讯作者：
Baud, Matthias G J