2-[2-Oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl)ethyl]-1H-isoindole-1,3(2H)-dione Chemical Properties

Boiling point:

546.7±43.0 °C(Predicted)

Density 

1.226±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL, clear (warmed)

form 

powder

pka

1.16±0.60(Predicted)

color 

white to beige

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.

Safety Information

Hazard Codes 

T

Risk Statements 

25-50/53

Safety Statements 

60-61

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

HazardClass 

IRRITANT

2-[2-Oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl)ethyl]-1H-isoindole-1,3(2H)-dione Usage And Synthesis

Description

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

Uses

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

Biochem/physiol Actions

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.

storage

Store at +4°C

References

[1] CHRISTIAN GRIMM. Small molecule activators of TRPML3.[J]. Chemistry & biology, 2010: 135-148. DOI:10.1016/j.chembiol.2009.12.016
[2] DONGBIAO SHEN. Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release.[J]. Nature Communications, 2012: 731. DOI:10.1038/ncomms1735
[3] WEISS N. Cross-talk between TRPML1 channel, lipids and lysosomal storage diseases.[J]. Communicative and Integrative Biology, 2012, 5 2: 111-113. DOI:10.4161/cib.20373
[4] JIANLONG ZOU. Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells.[J]. Journal of Neuroscience, 2015, 35 17: 6801-6812. DOI:10.1523/jneurosci.4442-14.2015

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