Abstract 14350: Identification of Celastramycin as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension -High-Throughput Screening of 5,562 Compounds

IntroductionPulmonary arterial hypertension (PAH) is a fatal disease characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). However, all the drugs in clinical use target pulmonary vascular dilatation, which may not be an effective target for patients with advanced PAH. Celastramycin is a benzoyl pyrrole-type compound originally found in a bacteria extract with anti-inflammatory effects. We aimed to discover a novel drug for PAH that inhibits PASMC proliferation.Methods and ResultsWe screened 5,562 compounds from original library using high-throughput screening (HTS) system. Among the compounds, we identified that celastramycin (CEL), a benzoyl pyrrole-type compound originally found in a bacteria extract, inhibited the proliferation of PASMCs from patients with PAH (PAH-PASMCs) in a dose-dependent manner with minimal effects on PASMCs from healthy donors (n=8 each, P