Allosteric inhibitors

Title: Allosteric Inhibitors: Unlocking New Avenues for Drug Development


Allosteric inhibitors are a class of drugs that modulate the activity of target proteins by binding to allosteric sites, remote from the active site, and modifying the protein’s conformation and function. This approach has gained considerable interest in drug discovery, offering several advantages over traditional inhibitors that target the active site. In this blog post, we will delve into the key points surrounding allosteric inhibitors, their mode of action, and their potential for developing new drugs.

Key Points:

  1. Understanding Allosteric Inhibition:
    Allosteric inhibition occurs when a molecule binds to an allosteric site on a protein, causing a conformational change that alters the protein’s activity. Allosteric inhibitors can either enhance or inhibit protein activity, depending on the protein’s function. By targeting allosteric sites, drugs may have lower toxicity and reduced potential for off-target effects compared to active site inhibitors.
  2. Advantages of Allosteric Inhibitors:
    Allosteric inhibition offers several advantages over traditional inhibitors that target the active site. Firstly, allosteric inhibitors may have a higher degree of selectivity, as allosteric sites are often unique to a particular protein or protein family. Secondly, allosteric inhibitors may have reduced toxicity, as they do not bind directly to the active site, reducing the risk of off-target interactions. Finally, allosteric inhibitors can overcome resistance mechanisms that arise from mutations in the active site of target proteins.
  3. Challenges of Allosteric Inhibition:
    One of the main challenges of allosteric inhibition is identifying suitable allosteric sites on target proteins, as these sites are often less characterized than active sites. Additionally, designing allosteric inhibitors that can effectively induce the desired conformational changes in the target protein can be challenging, as these changes may be complex and context-dependent. Finally, predicting the potential for off-target effects and toxicity of allosteric inhibitors can be difficult, as these effects may be dependent on the specific allosteric site and its interactions with other proteins.
  4. Examples of Allosteric Inhibitors:
    Several examples of allosteric inhibitors have been developed and are in clinical use or trials. For instance, the anti-cancer drug Imatinib (Gleevec) is an allosteric inhibitor of BCR-ABL, a fusion protein involved in chronic myelogenous leukemia. Similarly, the anti-coagulant drug Pridopidine binds to the dopamine receptor D2 at an allosteric site, leading to enhanced receptor activity. Other examples include Ruxolitinib, a Janus kinase inhibitor, and Effient, a platelet aggregation inhibitor.
  5. Future Directions:
    The use of allosteric inhibitors in drug development is an exciting field with considerable potential for future drug discovery. Advances in computational modeling and screening techniques may aid in the identification of suitable allosteric sites and the design of allosteric inhibitors. Additionally, the emergence of new technologies, such as cryo-electron microscopy and protein engineering, may contribute to a better understanding and manipulation of protein conformational changes.


Allosteric inhibitors represent a promising class of drugs that offer several advantages over traditional inhibitors for drug development. Targeting allosteric sites may offer a higher degree of selectivity, reduced toxicity, and the potential to overcome drug resistance. However, identifying suitable allosteric sites and designing effective allosteric inhibitors remains a challenge. Nevertheless, the development of allosteric inhibitors, such as Imatinib and Pridopidine, demonstrate the potential of this approach in drug discovery. By further exploring the mechanisms and applications of allosteric inhibition, we may unlock new avenues for developing safe and effective drugs to treat a wide range of diseases.