332382-54-4

ML-SA1 (332382-54-4) is a?TRPML 1,2 and 3 channel activator.1?Does not activate TRPM2, TRPV2, TRPV3, TRPC6 or TRPA1 channels.2?ML-SA1 robustly activates whole cell TRPML1-4A and whole-endolysosome TRPML1 and is comparable (10 μM) to the effect of the endogenous TRPML agonist, PI(3,5)P2?(1 μM).2?Thus it is a useful chemical tool for studying the functions of TRPMLs. It induces TRPML-mediated Ca2+?release from lysosomes which corrects trafficking defects and reduces cholesterol accumulation in Niemann-Pick type C macrophages.2,3?Reduces intralysosomal Ca2+?level rescuing abnormal lysosomal storage in FIG4-deficient cells.4

ML-SA1 has been used as a transient receptor potential cation channel mucolipin 1 (TRPML1/ML1) agonist.

ML-SA1 is a potent and selective cell permeable agonist of lysosomal mucolipin transient receptor potential channels (TRPML) 1, 2, 3 that significantly increases [Ca2+]cyt in HEK293 cells stably- or transiently-expressing mutant TRPML1 channels ML1-4A.

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1) Grimm?et al. (2010),?Small molecule activators of TRPML3; Mol. Chem. Biol.,?17?135 2) Shen?et al. (2012),?Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release; Nature Commun.,?3?731 3) Weiss?et al. (2012),?Cross-talk between TRPML1 channel, lipids and lysosomal storage diseases; Commun. Integer. Biol.,?5?111 4) Zou?et al. (2015),?Reactivation of lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells;J. Neurosci., 35?6801