ML-SA1

ML-SA1
Identifiers
	IUPAC name 2-[2-oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1-yl)ethyl]isoindole-1,3-dione;
CAS Number	332382-54-4;
PubChem CID	2880983;
ChemSpider	2155576;
ChEMBL	ChEMBL1527280;
Chemical and physical data
Formula	C22H22N2O3
Molar mass	362.429 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1CC(N(C2=CC=CC=C12)C(=O)CN3C(=O)C4=CC=CC=C4C3=O)(C)C;
	InChI InChI=1S/C22H22N2O3/c1-14-12-22(2,3)24(18-11-7-6-8-15(14)18)19(25)13-23-20(26)16-9-4-5-10-17(16)21(23)27/h4-11,14H,12-13H2,1-3H3; Key:KDDHBJICVBONAX-UHFFFAOYSA-N;

ML-SA1 is a chemical compound which acts as an "agonist" (i.e. channel opener) of the TRPML family of calcium channels. It has mainly been studied for its role in activating TRPML1 channels, although it also shows activity at the less studied TRPML2 and TRPML3 subtypes. TRPML1 is important for the function of lysosomes, and ML-SA1 has been used to study several disorders resulting from impaired lysosome function, including mucolipidosis type IV and Niemann-Pick's disease type C,[1][2][3][4] as well as other conditions such as stroke and Alzheimer's disease.[5][6]

References

Feng X, Xiong J, Lu Y, Xia X, Zhu MX (December 2014). "Differential mechanisms of action of the mucolipin synthetic agonist, ML-SA1, on insect TRPML and mammalian TRPML1". Cell Calcium. 56 (6): 446–56. doi:10.1016/j.ceca.2014.09.004. PMC 4252876. PMID 25266962.
Erkhembaatar M, Gu DR, Lee SH, Yang YM, Park S, Muallem S, et al. (February 2017). "2+ Signaling is Essential for Osteoclastogenesis and Bone Remodeling". Journal of Bone and Mineral Research. 32 (2): 385–396. doi:10.1002/jbmr.2986. PMID 27589205.
Gómez NM, Lu W, Lim JC, Kiselyov K, Campagno KE, Grishchuk Y, et al. (February 2018). "Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation". FASEB Journal. 32 (2): 782–794. doi:10.1096/fj.201700220RR. PMC 5888396. PMID 29030399.
Fine M, Schmiege P, Li X (October 2018). "2-mediated human TRPML1 regulation". Nature Communications. 9 (1): 4192. doi:10.1038/s41467-018-06493-7. PMID 30305615.
Wang Y, Jiang SW, Liu X, Niu L, Ge XL, Zhang JC, et al. "Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia". Oxidative Medicine and Cellular Longevity. 2018: 4612727. doi:10.1155/2018/4612727. PMID 30662583.
Hui L, Soliman ML, Geiger NH, Miller NM, Afghah Z, Lakpa KL, et al. "Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis". Journal of Alzheimer's Disease. 67 (1): 393–410. doi:10.3233/JAD-180941. PMC 6425476. PMID 30594929.

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[1] Feng X, Xiong J, Lu Y, Xia X, Zhu MX (December 2014). "Differential mechanisms of action of the mucolipin synthetic agonist, ML-SA1, on insect TRPML and mammalian TRPML1". Cell Calcium. 56 (6): 446–56. doi:10.1016/j.ceca.2014.09.004. PMC 4252876. PMID 25266962.

[2] Erkhembaatar M, Gu DR, Lee SH, Yang YM, Park S, Muallem S, et al. (February 2017). "2+ Signaling is Essential for Osteoclastogenesis and Bone Remodeling". Journal of Bone and Mineral Research. 32 (2): 385–396. doi:10.1002/jbmr.2986. PMID 27589205.

[3] Gómez NM, Lu W, Lim JC, Kiselyov K, Campagno KE, Grishchuk Y, et al. (February 2018). "Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation". FASEB Journal. 32 (2): 782–794. doi:10.1096/fj.201700220RR. PMC 5888396. PMID 29030399.

[4] Fine M, Schmiege P, Li X (October 2018). "2-mediated human TRPML1 regulation". Nature Communications. 9 (1): 4192. doi:10.1038/s41467-018-06493-7. PMID 30305615.

[5] Wang Y, Jiang SW, Liu X, Niu L, Ge XL, Zhang JC, et al. "Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia". Oxidative Medicine and Cellular Longevity. 2018: 4612727. doi:10.1155/2018/4612727. PMID 30662583.

[6] Hui L, Soliman ML, Geiger NH, Miller NM, Afghah Z, Lakpa KL, et al. "Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis". Journal of Alzheimer's Disease. 67 (1): 393–410. doi:10.3233/JAD-180941. PMC 6425476. PMID 30594929.