SMER3

SMER3 is a small molecule inhibitor of the RING E3 ubiquitin ligase RNF145 (and its yeast ortholog SCF^Met30). Originally identified in a chemical genetic screen as a 'Small Molecule Enhancer of Rapamycin' (SMER), it has been found to play a significant role in modulating fibrotic signaling in mammalian airway smooth muscle (ASM) cells. RNF145 acts as a negative regulator of 5' adenosine monophosphate-activated protein kinase (AMPK); by inhibiting RNF145, SMER3 restores AMPK activation and its subsequent antifibrotic effects. This leads to a reduction in the expression of extracellular matrix (ECM) proteins such as collagen and fibronectin, as well as a decrease in cell migration and airway remodeling. SMER3 is being investigated as a potential therapeutic agent for obstructive airway diseases, including asthma and COPD, where excessive ASM proliferation and fibrosis contribute to reduced lung function.

Other names

Small molecule enhancer of rapamycin 3