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A big future for small molecules: targeting the undruggable
Small molecule drugs have been the mainstay of the pharmaceutical industry for nearly a century. Defined as any organic compound with low molecular weight, small molecule drugs have some distinct advantages as therapeutics: most can be administered orally and they can pass through cell membranes to reach intracellular targets. They can also be designed to engage biological targets by various modes of action and their distribution can further be tailored, for example to allow for systemic exposure with or without brain penetration.
The rapid advancement of biopharmaceutical research and technology opens up possibilities for innovative and creative new approaches to developing small molecule drugs. 在澳门在线赌城娱乐, we combine our unique range of knowledge, skills and experience across multiple disciplines to keep discovering and developing potential new small molecule therapeutics. This includes utilising high-throughput screening, ensuring multifaceted characterisation of the molecules’ engagement with their targets and having deep expertise in chemical synthesis. 近年来, 预测的进步, structure-based design and imaging together with automation1, artificial intelligence and machine learning, have become important enablers to gain speed and improve the success rates of small molecule lead optimisation.
We are constantly advancing our capabilities to create new potential therapies for the future. 例如, modulating biological disease driving pathways at the RNA level opens up new opportunities for previous undruggable目标 and we are exploring the potential to use small molecule drugs to target RNA. New research we carried out in collaboration with the lab of Matthew Disney, 博士学位, at Scripps Research in the USA, 发表于 化学性质, describes the discovery of small molecules that are able to restart cellular production of vascular endothelial growth factor A (VEGF-A) in cellular models.2 VEGF-A is key to rebuilding blood vessels and muscle in damaged heart tissue and improving blood flow.
The ability to design small molecules capable of interacting with and modulating RNA could open new avenues to target challenging disease pathways that have previously been considered undruggable.
Other creative approaches we are exploring focus on the use of nanoparticles to direct small molecule drugs to specific cell types or minimise potential side effects.3
参考文献
1. Friis S, Johansson MJ, Ackermann L. Cobalt-catalysed C-H methylation for late stage drug diversification. 化学性质. 2020. 12, 511–519.
2. 汉尼夫，刘霞 等. Design of a small molecule that stimulates VEGFA informed from an expanded encyclopedia of RNA fold-small molecule interactions. 化学性质. http://doi.org/10.1038/s41557-020-0514-4
3. Tyagi P, Pechenov S, RiosDoria J 等. Evaluation of Pyrrolobenzodiazepine-Loaded Nanoparticles: A Targeted Drug Delivery Approach. 2019. 108(4): 1590-1597.
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We know that however innovative our science, however effective our medicines and delivery, to achieve all we want to achieve, 澳门第一赌城在线娱乐不能单独完成.