Monoclonal antibodies and ligand mimics are both able to bind specifically to a target protein. Ligand mimics target the orthosteric site, blocking the endogenous ligand from binding, and either activating or inhibiting the function of the target.
Monoclonal antibodies (Mabs) are able to bind to almost any target, including ‘non-druggable targets’ due to their larger binding interaction area. This allows for a wider range of targets to be produced. Mabs can be produced in vitro, with hybridoma cells to produce large quantities of antibody that can then be intravenously administered.
Ligand mimics are small-molecule drugs binding to the orthosteric site. By using screening and design, these molecules can be made highly specific for their intended target. De novo synthesis of ligand mimics is possible where the target molecule is understood and the structure known. These drugs are typically easier to administer, normally orally or rectally. By binding to the target, ligand mimics can activate or suppress its activity. An example could include aspirin (salicylic acid), binding to cyclooxygenase-2 (COX-2) to prevent the formation of prostaglandins and eicosanoids.
Mabs are more frequently used with rarer or more complex diseases, as they are easily able to be generated and are generally safe. For example, SARS-CoV-2 infection was able to be treated with Mabs (or convalescent plasma, through largely the same process), conveying passive immunity. Cimzia, a drug used to treat arthritis and other related conditions, is a Mab sequestering tumour necrosis factor alpha (TNF-alpha), reducing the inflammatory response in impacted joints.
Small molecule drugs, ligand mimics, are generally better suited to common conditions. They are (usually) able to be administered at home, reducing the cost to health services. Ligand mimics can also include small peptides. These may need to be administered directly into the systemic circulation, preventing damage from digestion. Small peptides could include hormones – these are administered by simple subcutaneous injection or a topical gel.
Different approaches are necessary to treat different conditions. Certain approaches may be more effective and cheaper, improving health outcomes for the patient while reducing the cost to health services.