Stemcell, 74202, SMER28

SMER28, a bromo-substituted quinazoline, was first identified as a small-molecule enhancer of rapamycin (SMER; Sarkar et al.). SMER28 induces autophagy by increasing autophagosome synthesis and enhancing the clearance of model autophagy substrates (Renna et al.).

REPROGRAMMING

· As a component of a neural reprogramming cocktail, SMER28 reprograms mouse fibroblasts into induced neural stem cell-like cells (Zhang et al.).

DISEASE MODELING

· Enhances clearance of autophagy substrates including mutant huntingtin in Huntington's disease and A53T α-synuclein in familial Parkinson's disease (Sarkar et al.).

· Through autophagy factor ATG5, stimulates erythropoiesis and up-regulates expression of globin genes in both in vitro and in vivo models of Diamond-Blackfan anemia (Doulatov et al.).

· Decreases the level of indicators of Alzheimer's disease (amyloid-β peptide and the amyloid precursor protein [APP]-derived fragment) via the autophagy-related protein 5-dependent pathway (Tian et al.).