TFEB activator 1

TFEB activator 1 is an orally effective, mTOR-independent activator of TFEB. TFEB activator 1 significantly promotes the nuclear translocation of Flag-TFEB with an EC50 of 2167 nM. TFEB activator 1 enhances autophagy without inhibiting the mTOR pathway and has the potential for neurodegenerative diseases treatment[1].

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Neurological Disease

EC50: 2167 nM (Flag-TFEB nuclear translocation)[1]

TFEB activator 1 (Compound C1) activates TFEB (transcription factor EB) by directly binding to TFEB and promotes its entry into the nucleus, without affecting TFEB phosphorylation or inhibiting the activities of MTOR and MAPK1/ERK2-MAPK3/ERK1[1]. TFEB activator 1 (1 μM; for 12 h) significantly increases the levels of LC3B-II, the lipidated and phagophore- or autophagosome-associated form of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) in N2a cells[1]. TFEB activator 1 (0.2-1 μM) dose-dependently increases the levels of LC3-II and SQSTM1/p62 (sequestosome 1) in N2a cells[1]. Western Blot Analysis[1] Cell Line: N2a cells Concentration: 0, 0.2, 0.4, 0.6, 0.8 and 1 μM Incubation Time: 12 hours Result: Treatment dose-dependently increased the levels of LC3-II and SQSTM1/p62 (sequestosome 1).

The medium lethal dose (LD50) value of TFEB activator 1 (Compound C1) is 175 mg/kg in the acute toxicity assay (single-dose i.v. tail vein injection; in rats) [1]. Short-term oral administration of TFEB activator 1 (low dosage 10 mg/kg and high dosage 25 mg/kg; for 24 h) dose-dependently increases the expression of LC3B-II and TFEB in the liver, frontal cortex and striatum of the brain[1]. Chronic administration of TFEB activator 1 (10 mg/kg per day; orally administered by gavage) activates TFEB and enhances autophagy in rat brains[1]. Animal Model: Adult male Sprague-Dawley (SD) rats weighing 350 to 400 g[1] Dosage: 10 mg/kg and 25 mg/kg Administration: Short-term oral administration; for 24 hours Result: Activated TFEB and enhanced autophagy and lysosome biogenesis in rat brain. Animal Model: Adult male Sprague-Dawley (SD) rats weighing 350 to 400 g[1] Dosage: 10 mg/kg Administration: Chronic oral administration; daily; for 21 days Result: Activated TFEB and enhanced autophagy in rat brains.

[1]. Song JX, et al. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition. Autophagy. 2016 Aug 2;12(8):1372-89.