Small molecules have driven drug progress over the past century as pharmaceutical companies have significantly advanced drug development. Large-molecule drugs (biologics) differ from small-molecule drugs.
Large-molecule drugs derive from proteins, which gives them a complex three-dimensional structure that makes their molecular weight heavier, less stable, and more costly to manufacture than small-molecule drugs. Because of their size, large-molecule drug administration must happen intravenously, while individuals can swallow small-molecule drugs.
Drugs made from small molecules are tiny enough to pass through cell membranes, meaning they can reach targets inside cells to interact with molecules and bring the desired medicinal effect. Small molecules can bind to enzymes to block their catalytic activities, stopping the processes that cause diseases. Small molecules can also bond to receptor proteins on the cell surface, blocking or activating them and affecting intercellular communication. Additionally, small molecules can bind to ion channels - proteins that move ions in and out of cells, regulating crucial bodily functions such as heart rate.
Small molecule drugs come in various dosage forms, catering to diverse patient needs, such as oral medication for those with injection phobias. Their extended shelf-life at room temperature enables convenient storage and self-administration, particularly benefiting vulnerable populations like the elderly and chronically ill by reducing the burden on healthcare professionals and minimizing pharmacy visits.
The therapeutic application of small-molecule drugs is broad. In cancer treatment, these drugs have proven more efficient and safer than traditional chemotherapy due to their ability to target specific proteins involved in the disease’s progression. Anti-cancer drugs from small molecules inhibit proteins that drive tumor growth and survival. The US Food and Drug Administration has approved 89 small-molecule drugs for cancer treatment. However, drug resistance over time and low efficiency are among the challenges. Pharmaceutical researchers are combining small-molecule drugs with immune-therapy antibodies and using other techniques to advance the treatment of some types of cancer.
Various technologies are proving essential in small-molecule drug development for new treatments. Artificial intelligence (AI) also enhances small-molecule drug development. Scientists leverage AI and machine learning to screen vast libraries of compounds and analyze patterns in large datasets to predict efficacy and safety, reducing costly late-stage failure. AI can also design molecules, repurpose existing drugs, and assist in planning how to make these medicines.
Technology enables small-molecule drugs to target more proteins in the body. Usually, these drugs only attach to specific sites on certain enzymes and receptors. But now, scientists have developed new ways to make drugs interact with proteins. Some drugs can now form strong and long-lasting connections with certain parts of proteins, making them more effective. These new approaches expand the number of proteins small-molecule drugs can target, opening new possibilities for disease treatment.
However, many small molecule drugs still have drawbacks, such as low solubility, that need addressing. Conventional small-molecule drugs can also not adapt to bodily states or changes. For instance, beta-blockers, medications to reduce heart rate, operate the same way at rest and during exercise when the heart needs to pump harder and provide more oxygen-rich blood. Overcoming these hurdles necessitates all available tools, including new approaches to research and development.
