BIO5192 is a Selective and Potent Integrin α4β1 (VLA-4) Inhibitor

Hematopoietic stem and progenitor cells (HSPCs) reside is in a specialized microenvironment. It also refers to the stem cell niche, which regulates critical HSPC processes, such as self-renewal and differentiation. Trafficking of HSPCs between the bone marrow, peripheral blood, and secondary organs is a dynamic process. HSPC mobilization and homing may be closely related to two critical pathways. The one involves the α4β1 integrin, VLA-4, with its ligand VCAM-1, and the other is chemokine receptor CXCR4 and its ligand SDF-1. In this study, BIO5192 is a small molecule inhibitor of VLA-4. It results in a 30-fold increase in the mobilization of murine HSPCs over basal levels. when plerixafor (AMD3100), a small molecule inhibitor of the CXCR-4/SDF-1 axis, is combined with BIO5192, there has an additive effect on HSPC mobilization. Furthermore, the combination of granulocyte colony-stimulating factor (G-CSF), BIO5192, and plerixafor enhance mobilization by 17-fold compared with G-CSF alone.

BIO5192 is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM). It also selectively binds to α4β1 (IC50=1.8 nM) over a range of other integrins. Moreover, it results in a 30-fold increase in the mobilization of murine HSPCs over basal levels. The combination of BIO5192 and Plerixafor exert an additive effect on progenitor mobilization. BIO5192 hydrate delays paralysis associated with EAE (experimental autoimmune encephalomyelitis).It shows the terminal half-life is 1.1 hours. In addition, it shows half-lives of 1.7, 2.7, and 4.7 hours, respectively.

In summary, BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem, and progenitor cells. It will be a valuable reagent for assessing alpha 4 beta 1 biology and may provide a new therapeutic for the treatment of human inflammatory diseases.


Ramirez P, et al. Blood. 2009;114(7):1340‐1343.