Zharp1-211 is a selective and potent RIPK3 inhibitor that significantly reduces the expression of JAK/ stat1-mediated chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and inhibits graft-versus-host disease (GVHD) for gastrointestinal inflammation.

Zharp1-211 was highly potent for blocking TNF-induced necroptosis in human colon cancer HT-29 cells and mouse fibroblast L929 cells, and reduced IFN-γ–induced STAT1 activation in mouse intestinal crypt cells by affecting the JAK1/STAT1 pathway. [1]

Oral administration of Zharp1-211 (10 mg/kg) starting on day 7 after T cell transplantation significantly reduced GVHD severity and improved survival in multiple mouse models. Zharp-211 alleviated inflammation in the colon, small intestine, liver, and skin, preserved intestinal stem and Paneth cells, suppressed chemokine expression, reduced alloreactive T and CXCR3⁺ T cells, and inhibited STAT1 activation and necroptosis/apoptosis in the gut. [2]