Integrins are adhesion receptors that mediate many of the key cell-cell and cell-extracellular matrix interactions. There are 24 known integrins in humans, all of which are heterodimers composed of an α-subunit and a β-subunit (noncovalent α/β heterodimers composed from 18 different α subunits and 8 β subunits).
Integrins lie at the heart of many cellular biological processes. These receptors can signal bi-directionally, both “inside-out” and “outside-in”, to control a variety of biological processes, such as development, cell attachment, migration, division, growth, differentiation, survival, and apoptosis. At times, integrins utilize highly dynamic changes in their structure to regulate biology beyond typical means.
Because of their central roles in almost all phases of human biology as well as in the pathophysiology of many diseases, their potential to be therapeutically targeted is now widely recognized. Several integrin inhibitors have been approved by the Food and Drug Administration for the treatment of inflammatory bowel disease (Entyvio®, Tysabri®), multiple sclerosis (Tysabri®), psoriasis (Raptiva®), acute coronary syndrome (Reopro®, Aggrastat®, Integrilin®), and dry eye disease (Xiidra®).
However, there has been a notable absence of therapeutic success with orally bioavailable small molecule integrin inhibitors. The breakthrough findings by our scientific founder, Dr. Tim Springer, have shed light on the features of productive small-molecule integrin inhibitors, enabling for the first-time discovery of truly novel oral small molecule antagonists.