Integrin α4β1 (VLA-4) promotes the immune system’s inflammatory response by helping white blood cells move to tissues that need inflammation. Specifically, VLA-4 is a key factor in cell adhesion. Besides, the α – and β – adrenoceptors are composed of two distinct integrin subunits. Moreover, the main ligands of VLA-4 include VCAM-1 and fibronectin. Furthermore, VLA-4, especially α subunit, is essential for the localization and circulation of progenitor cells. One way to increase cell retention is to target adhesion receptors expressed on the surface of integrin family stem cells and progenitor cells. Furthermore, direct targeting of key integrins with small molecular agonists may be an effective way to enhance cell retention in stem cell therapy. VLA-4 is critical for progenitor cell homing to ischemic sites, as well as for cell fusion in stem cell therapy. THI0019 is a potent integrin α4β1 (VLA-4) agonist.

THI0019 is a potent integrin α4β1 (VLA-4) agonist.

How does THI0019 work on the target? Let’s study it together. In the beginning, THI0019 is a potent integrin α4β1 (VLA-4) agonist with an EC50 range of 1-2 μM. Nonetheless, THI0019 induces stem/progenitor cells adhesion. THI0019 also regulates adhesion mediated by α4β7, α5β1, and αLβ2.

In the second place, THI0019 shows a dose-dependent enhancement in cell binding with an EC50 of 1.7 μM when Jurkat cells bound to CS1-conjugated BSA. Importantly, THI0019 induces an even more pronounced 100-fold increase in Jurkat cell binding, with an EC50 of 1.2 μM when using VCAM-1 as the ligand. Particularly, THI0019 induces a dose-dependent increase in EPC binding to VCAM-1 (EC50 of 3.7 μM). By the way, THI0019 facilitates the rolling and spreading of cells on VCAM-1 and the migration of cells toward SDF-1α.

All in all, THI0019 is a potent integrin α4β1 (VLA-4) agonist.


Peter Vanderslice, et al. J Biol Chem. 2013 Jul 5;288(27):19414-28.