allosterici

Allosterici are a class of pharmacological agents that modulate the activity of receptors or enzymes through allosteric sites, which are distinct from the primary active site. Unlike traditional drugs that bind directly to the active site of a target protein, allosteric modulators exert their effects by binding to secondary sites on the protein structure, causing conformational changes that alter the protein's function.

These compounds can be categorized into positive allosteric modulators, which enhance the activity of the target protein, and negative allosteric modulators, which reduce its activity. Positive allosteric modulators increase the affinity of the primary ligand for its binding site or increase the efficacy of the receptor response, while negative allosteric modulators produce the opposite effects.

The allosteric approach to drug development offers several advantages over traditional orthosteric targeting. Allosteric modulators often demonstrate greater selectivity, as allosteric sites tend to be more diverse between different protein subtypes than active sites. This selectivity can lead to fewer side effects and improved therapeutic windows. Additionally, allosteric modulators typically exhibit saturable effects, meaning their influence is naturally limited, which can provide improved safety profiles compared to orthosteric drugs that may cause unlimited receptor activation or blockade.

The mechanism of allosteric modulation involves cooperative interactions between the allosteric site and the primary binding site. Binding of an allosteric modulator can either facilitate or inhibit the binding of the endogenous ligand, depending on whether it acts as a positive or negative modulator. This cooperativity is described by allosteric parameters that quantify the strength of these interactions.

Allosteric drugs have shown promise in treating various conditions, including neurological disorders, cardiovascular diseases, and metabolic conditions. Examples include benzodiazepines, which act as positive allosteric modulators of GABA receptors, and some calcium channel modulators used in hypertension treatment.