Fragment-based drug discovery for the sweet tooth of prostate cancer

每八名男性中就有一人在一生中患上前列腺癌，这使得改进治疗方案成为绝对必要的。糖结构改变，也被称为糖链，是前列腺癌的一个一贯特征，但在药物开发中却被极大地忽视了。最近，我们确定了一种糖基化酶作为一种新的治疗靶点，并为开发更好的前列腺癌治疗方法提供了一个令人兴奋的机会。该项目由英国前列腺癌和化学生物学研究所共同资助，将专注于针对这种酶的基于片段的药物发现。我们将结合新的可用的化学空间和建模方法来生成具有合适相互作用曲线的铅化合物。将进行生物学评估，以设想一种打击糖基化的药物，糖基化是前列腺癌的甜食。我们正在寻找在化学方面有很强背景的申请者，最好是有一些药物发现/药物化学方面的经验。您将领导一个协作项目，需要与PI协调、保存记录和致力于可重复、安全的实验室工作的出色技能。该项目将在伦敦帝国理工学院全新的分子科学研究中心进行，帝国理工学院是英国化学科学的旗舰，拥有最先进的实验室空间和设备。它以与纽卡斯尔和萨拉戈萨(西班牙)的合作者合作为特色，以及在伦敦市中心的弗朗西斯·克里克研究所借调的可能性。

One in eight men get prostate cancer in their lifetime, making improved therapy options an absolute necessity. Altered sugar structures, also called glycans, are a consistent feature of prostate cancer but are vastly underexplored in drug discovery. Very recently, we have identified a glycosylation enzyme as a novel therapeutic target and an exciting opportunity to develop better treatments for prostate cancer. This project, co-funded by Prostate Cancer UK and the Institute of Chemical Biology, will focus on fragment-based drug discovery target this enzyme. We will combine newly-available chemical space and modelling approaches to generate lead compounds with suitable interaction profiles. Biological evaluation will be performed to envisage a drug that hits glycosylation, the sweet tooth of prostate cancer. We are looking for applicants with a strong background in chemistry, ideally with some experience in drug discovery/medicinal chemistry. You will be leading a collaborative project, requiring excellent skills in coordinating with PIs, record-keeping and dedication for reproducible, safe laboratory work. This project will be carried out at the brand-new Molecular Sciences Research Hub at Imperial College London, a flagship of chemical sciences in the UK with state-of-the-art laboratory space and equipment. It features work with collaborators in Newcastle and Zaragoza (Spain), as well as the potential for a secondment at the Francis Crick Institute in central London.