aminopterin (EC0746) / Novartis - LARVOL DELTA

Targeting folate receptor beta on monocytes/macrophages renders rapid inflammation resolution independent of root causes. (PubMed, Cell Rep Med) - "Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation...We further show that EC2319 suppresses interleukin-6/interleukin-1β release by FRβ monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development."

Journal • Glomerulonephritis • Immunology • Inflammation • Lupus Nephritis • Nephrology • Ocular Inflammation • Ophthalmology • Rheumatology • Uveitis • IL1B • IL6

A Novel Treatment for Glomerular Disease: Targeting the Activated Macrophage Folate Receptor with a Trojan Horse Therapy in Rats. (PubMed, Cells) - "Using a macrophage-mediated anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in WKY rats, we investigated the effect of a novel folic acid-aminopterin (AMT) conjugate (EC2319) designed to intracellularly deliver AMT via the FR...Notably, treatment with methotrexate (MTX), another folic acid antagonist related to AMT, did not protect from kidney damage...In nephritic kidneys, FRβ was expressed on periglomerular macrophages and macrophages present in the crescents, but its expression was not observed in normal kidneys. These data indicate that selectively targeting the activated macrophage population could represent a novel means for treating anti-GBM GN and other acute crescentic glomerulonephritis."

Journal • Preclinical • Fibrosis • Glomerulonephritis • Immunology • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • CCL2 • TGFB1