molecules of the month

Overview. Cyclin-dependent kinase (CDK2) is a target of recent interest, but selectivity has been challenging to obtain. This molecule provides an interesting example of AI being applied to lead generation. Macrocycles can be challenging to design rationally, but can lead to a variety of favorable properties (e.g. in addressing resistance or brain penetration; see article on Turning Point) and novel intellectual property space. AI could potentially assist with identifying promising starting points. While the authors admit the limitations of this approach and demonstrated superiority of human design, this case study illustrates proof-of-concept for how AI can help assist lead generation by human designers and provides a practical tool for generating viable macrocyclic starting points that could be valuable in kinase…