Rholistiq

Belumosudil is a potent and selective inhibitor of Rho-associated, coiled coil containing protein kinase-2 (ROCK2). In chronic graft versus host disease (GVHD), naïve thymus cells (T-cells) are skewed to a pro-inflammatory T-cell phenotype, known as T-helper 17 (Th17) cells, with aberrant activation of ROCK2 promoting the synthesis of the pro-inflammatory cytokines interleukin (IL) 17 and IL-21. ROCK2 activation is also recognised to promote pro-fibrotic processes and suppress regulatory T cells. In vitro, belumosudil was shown to suppress IL-17 and IL-21 release from human peripheral blood mononuclear cells and to shift the Th17/regulatory T-cells (Treg) balance of human T cells (mediated via downregulation of signal transducer and activator of transcription (STAT)3 phosphorylation and upregulation of STAT5 phosphorylation, respectively). Anti-fibrotic activity was evident for belumosudil in experiments with cultured human lung fibroblasts. In vivo, belumosudil demonstrated efficacy in mice models of chronic GVHD.