Medicinal Chemistry behind Capivasertib Discovery: Seventh Magic Bullet of the Fragment-based Drug Design Approved for Oncology

A new pharmacotherapy prescribed by medical oncology professionals for breast cancer patients emerged at the end of last year. Capivasertib is the first approved inhibitor targeting protein kinase B (Akt), and has been manufactured as the active ingredient in the oral medicine Truqap^TM. This compound has joined the prestigious list of successful pharmacological agents that were discovered by exploiting a fruitful medicinal chemistry paradigm named fragment-based drug design. In this article, we provide a brief theoretical basis for this strategy and present a speculative overview of the experimental and computational workflows involved in the discovery of this small-molecule antitumor drug, highlighting some of the details of its rational design, which were crucial to the success of the campaign, and culminated in the recent approval of the seventh magic bullet derived from molecular fragments.