Discovering drugs isn’t a one-size-fits-all process. It’s a mix of strategies, blending creativity, science, technology, and even luck. A drug discovery program aims to produce preclinical candidate molecules that show evidence of biological activity against a disease target. From serendipitous breakthroughs to AI-designed molecules, here’s a rundown on how scientists find medicines that change our lives.

Old-School Discovery

Phenotypic drug discovery (PDD) is the classic method where scientists test compounds on cells, tissues, or organisms to see what happens. There is no specific target; it is just pure trial and error. It’s like tossing ideas at the wall and waiting for one to stick. This serendipitous strategy led to the discovery of artemisinin, a lifesaving antimalarial drug.

Sniper Method

Target-based drug discovery (TDD) takes a more focused approach. Here, researchers zero in on a specific biological target, like a rogue protein driving disease, and develop drugs to neutralize it. It’s all about precision, like with the drug pimavanerin (Nuplazid) used to treat Parkinson’s disease psychosis.

Speed Dating

When time is of the essence, high-throughput screening (HTS) steps in. This approach uses automation and robotics to test thousands—or even millions—of molecules against a target at lightning speed. Think of it as the molecular version of speed dating. Many antiviral drugs, including those for Covid-19, owe their origins to this fast-paced method.

Cocktail Fodder

Notably, approximately one-third of transformative drugs approved by the U.S. FDA are repurposed products. Sildenafil, developed initially for hypertension, famously pivoted into Viagra.

Puzzle-Solving Method

Structure-based drug discovery (SBDD) leans heavily on visuals. By mapping the 3D structure of a target protein—using tools like X-ray crystallography—researchers can design drugs that fit like a key in a lock. This method was pivotal in creating HIV protease inhibitors, a significant win in the fight against the virus.

AI Discovery

Today’s cutting-edge tools include computational drug discovery, where AI and algorithms do the heavy lifting. Researchers model and predict how molecules interact with disease targets, cutting down on expensive and time-consuming lab experiments. A drug you may have taken yourself, oseltamivir (Tamiflu), indicated for influenza, was discovered using these methodologies.

Drug Discovery 101

The goal of a drug discovery program is to advance candidate molecules into a preclinical development program. While this article lists the various methodologies to do so, there are specific steps common in all these approaches that scientists take to achieve this goal. Small Molecule Drug Discovery Primer 101 teaches these essential steps. From identification to optimization, this microcourse demonstrates how scientists refine small molecules before they undergo preclinical and clinical development. Use coupon code SMDDGET15 to get 15% off until January 31, 2025. Register now!