BIO 5192

BIO5192 is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM). BIO5192 selectively binds to α4β1 (IC50=1.8 μM) over a range of other integrins. BIO5192 results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Cytoskeleton >> Integrin

The combination of BIO5192 (1 mg/kg; i.v.) and Plerixafor (5 mg/kg; s.c.) exert an additive effect on progenitor mobilization[1]. BIO5192 (30 mg/kg; s.c; bid; during days 5 through 14) delays paralysis associated with EAE (experimental autoimmune encephalomyelitis)[2]. BIO5192 (1 mg/kg, i.v.) shows the terminal half-life is 1.1 h. IO5192 (3, 10, and 30 mg/kg; s.c.) shows half-lives of 1.7, 2.7, and 4.7 h, respectively. The blood plasma curves show that the AUC for the s.c. route of administration increased about 2.5-fold from 5,460 h*ng/ml for the 3 mg/kg dose to 14,175 h*ng/ml for the 30 mg/kg[1]. Animal Model: C57BL/6J x 129Sv/J F1 mice[1] Dosage: 1 mg/kg (with Plerixafor: 5 mg/kg) Administration: I.v. Result: Exerted an additive effect on progenitor mobilization. Animal Model: Healthy female Lewis rats weighing 150g[2] Dosage: 30 mg/kg Administration: S.c; bid; during days 5 through 14 Result: Showed a 3-day delay in onset of disease.

[1]. Ramirez P, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114(7):1340‐1343.

[2]. Leone DR, et al. An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2003;305(3):1150‐1162.