Chemistry is all about making bonds, particularly covalent ones in which atoms share electrons. And some of the world’s longest-known pharmaceuticals—including the anti-inflammatory aspirin and the antibiotic penicillin V—act by forming covalent bonds with their biological targets.

But drugmakers have generally avoided developing such drugs, fearing that the molecules would do more harm than good by binding to nontarget proteins or triggering immune responses. Instead, pharmaceutical scientists have focused on molecules that bind reversibly through noncovalent interactions.

The recent success of several covalent anticancer drugs has demonstrated that the fears around covalent drugs are, if not unfounded, perhaps overblown.

In this report, you’ll discover what chemists have learned about covalent drugs that has turned them into a mainstay of drug development. You’ll learn the chemistry behind targeting proteins previously considered to be undruggable. You’ll meet the scientists developing new tools to demonstrate the selectivity of drug candidates. And you’ll encounter the start-ups taking the molecules into the clinics.