BRD2889

BRD2889 is a small molecule piperlongumine (PL) analog identified through computational drug repurposing for the treatment of pulmonary arterial hypertension (PAH). It was discovered using the EDDY (Evaluating Differential DependencY) algorithm, which analyzes RNA sequencing data to identify chemotherapeutics that target specific gene clusters rewired in disease states. BRD2889 acts as an inhibitor of glutathione S-transferase P1 (GSTP1). In the context of PAH, GSTP1 typically catalyzes the glutathionylation of the iron-sulfur (Fe-S) biogenesis protein ISCU, increasing its stability under hypoxic conditions. By inhibiting GSTP1, BRD2889 disrupts this axis, leading to restored Fe-S-dependent mitochondrial Complex I activity and oxygen consumption, thereby ameliorating pathogenic apoptosis in pulmonary arterial endothelial cells. Preclinical studies in IL-6 transgenic mouse models have demonstrated that BRD2889 improves hemodynamic and molecular manifestations of the disease.

Other names

piperlongumine analog