Discovery of Zharp1-163 as a dual inhibitor of ferroptosis and necroptosis for the treatment of inflammatory disorders and kidney injury.

Dysregulation of cell death plays a critical role in the onset and progression of numerous human diseases. Distinct forms of regulated cell death, such as necroptosis and ferroptosis, have been implicated in the pathogenesis of various conditions, including neurodegenerative disorders and acute kidney injury. Strategies that concurrently target both necroptosis and ferroptosis present significant potential for improving therapeutic outcomes.

A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis.

Intestinal epithelial cells (IECs) are implicated in the propagation of T-cell-mediated inflammatory diseases, including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD after allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver.

Interferon-mediated repression of miR-324-5p potentiates necroptosis to facilitate antiviral defense.

Mixed lineage kinase domain-like protein (MLKL) is the terminal effector of necroptosis, a form of regulated necrosis. Optimal activation of necroptosis, which eliminates infected cells, is critical for antiviral host defense. MicroRNAs (miRNAs) regulate the expression of genes involved in various biological and pathological processes.

Synthesis and characterization of potent RIPK3 inhibitors based on a tricyclic scaffold.

Necroptosis is an important form of regulated cell death involved in inflammatory diseases, degenerative diseases and cancer. RIPK3 is an interesting target for intervention of necroptosis-associated diseases. Herein the authors report the synthesis of a series RIPK3 inhibitors under the guidance of structure-based drug design which leads to the identification of compound .

Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis.

Purpose: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL.