What is Allosteric Modulation?

Allosteramers are potent (IC50<5nM), orally active, drug candidates that bind specifically to their target receptors. Allosteramers™ are designed to bind “allosterically” to their targets; that is, they block the receptor's signal by binding in an area remote from natural receptor binding site, or "ligand site". Thus an Allosteramer™ can block a signal without competing with the body's natural ligands. The resulting drug candidates are designed to have the potency and specificity similar to that of a monoclonal antibody with the oral delivery capability of a small molecule.

Allosteric Modulators are Selective

The other aspect about allosteric modulation is its effect on the structure of receptors. Given that receptors are composed of multiple functional domains and often result in different types of signals that get conveyed to the cell, it is clear that the structural changes of any given receptor are quite complex. When a natural ligand is blocked from binding to its receptor, then all the corresponding signal pathways are blocked. However, if only certain domains are blocked, or only some structural changes are blocked as in the case with allosteric modulators, then only specific but not all signals are interfered with. The ability to block only some signals is a unique aspect seen only with allosteric modulators. This is is termed “pharmacological selectivity.”

In this way, allosteric modulators can offer a higher level of selectivity than typical “competitive” drugs (called orthosteric inhibitors). This could allow the development of more selective and safer drugs, for example, drugs that affect only certain signals and not others. This effect has been well-characterized in the literature, especially in relation to GPC receptors, and corroborated by Allostera with cytokine receptors.