VX-702 is a selective inhibitor of p38α MAPK with IC50 value ranges from 4 nM to 20 nM [1].
P38 mitogen-activated protein kinases (p38 MAPK), also named as MAPK14, are a class of mitogen-activated protein kinases and play an important role in a signaling cascade controlling cellular responses to cytokines and stress [1-3].
VX-702 is a potent p38α MAPK inhibitor and is designed as for greater affinity and greater selectivity compared with the first reported p38α MAPK inhibitors. When tested with PLTs (platelets), VX-702 caused better maintenance of PLT mitochondrial, functional, structural and metabolic parameters during 7 days storage and restored PLTs properties following an extended interruption of agitation to levels of continuously agitated PLTs [2, 4].
In the isolated perfused rat kidney (IPRK) model, administration of VX-702 at a range of doses between 100 and 600 ng/mL showed linear excretion and the clearance data were consistent with net reabsorption by the kidney. Further, VX-702 was showed not a substrate for renal organic anion and organic cation transport systems [3].
References:
[1]. Kuliopulos, A., R. Mohanlal, and L. Covic, Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost, 2004. 92(6): p. 1387-93.
[2]. Skripchenko, A., et al., An inhibition of p38 mitogen activated protein kinase delays the platelet storage lesion. PLoS One, 2013. 8(8): p. e70732.
[3]. Tamhane, M., et al., Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model. Drug Dev Ind Pharm, 2010. 36(3): p. 315-22.
[4]. Wagner, S.J., et al., Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 degrees C by a p38MAPK inhibitor, VX-702. Vox Sang, 2015. 108(3): p. 226-32.