smallmolecule

Small molecules are low molecular weight organic compounds that can regulate biological processes by binding to biomolecules such as proteins, nucleic acids, or membranes. In contrast to large biopolymers like proteins and nucleic acids, small molecules are typically defined by relatively small size and often by properties that support cell permeability and oral bioavailability. They include synthetic chemicals, natural products, and their derivatives.

Small molecules can modulate biological function by inhibiting or activating enzymes, blocking receptors, or altering signaling pathways. They tend to act through non-covalent interactions such as hydrogen bonding, ionic interactions, and hydrophobic effects, although some covalent inhibitors form bonds with their targets. Their versatility makes them central to pharmacology, chemical biology, and medicinal chemistry, where they are used as drugs, research probes, and tool compounds.

Drug discovery relies on libraries of small molecules and strategies such as high-throughput screening, structure-based design, and fragment-based lead discovery. Guidelines like Lipinski's Rule of Five help assess druglikeness by considering properties such as molecular weight, lipophilicity, and hydrogen bonding capability, although there are many successful exceptions. Properties such as solubility, stability, and synthetic accessibility shape how readily a small molecule can be developed into a therapeutic agent.

Examples of well-known small molecules include aspirin (acetylsalicylic acid), caffeine, morphine, and acetaminophen. Small molecules also underpin many agrochemicals, dyes, and catalysts. While they offer advantages in manufacturability and pharmacokinetic predictability, they can also cause off-target effects and toxicity, especially when target selectivity is limited.