SMER18 is a small molecule enhancer of rapamycin which act as a mTOR-independent autophagy inducer. Target: mTOR SMER18 induces autophagy independently of Rapamycin in mammalian cells, enhancing the clearance of autophagy substrates such as mutant huntingtin and A53T alpha-synuclein, which are associated with Huntington’s disease and familial Parkinson’s disease, respectively. SMER18 acts either independently or downstream of the target of Rapamycin, attenuates mutant huntingtin-fragment toxicity in Huntington’s disease cell and Drosophila melanogaster models, which suggests therapeutic potential.

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• [1]. Sarkar S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol. 2007 Jun;3(6):331-338.