PGC-005-101

PGC-005-101 (also known as 101-PGC-005) is an investigational, macrophage-targeted, pH-sensitive dexamethasone conjugate (prodrug) developed by 101 Therapeutics. It is designed to selectively target activated CD206-positive (mannose receptor-positive) macrophages, which are key drivers of pathological inflammation in severe infectious and autoinflammatory diseases. Upon binding to CD206, the prodrug is internalized via receptor-mediated endocytosis, and the acidic environment of the endosome triggers the release of active dexamethasone intracellularly. This targeted delivery induces apoptosis of pathogenic macrophages and dampens hyperinflammation while avoiding systemic glucocorticoid exposure and preserving the hypothalamic-pituitary-adrenal (HPA) axis. PGC-005-101 has been evaluated in clinical trials for COVID-19-associated inflammatory disease and acute respiratory distress syndrome (ARDS), and has received FDA Rare Pediatric Disease Designation for systemic juvenile idiopathic arthritis (sJIA) flares.

Other names

101-PGC-005 ('005)mannose-linked dexamethasone prodrugmannose-targeted dexamethasone conjugate