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Chemical compound
ML-SA1
2-[2-oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1-yl)ethyl]isoindole-1,3-dione
CAS Number
PubChem
CID
ChemSpider
ChEMBL
CompTox Dashboard (
EPA )
Formula C 22 H 22 N 2 O 3
Molar mass 362.429 g·mol−1 3D model (
JSmol )
CC1CC(N(C2=CC=CC=C12)C(=O)CN3C(=O)C4=CC=CC=C4C3=O)(C)C
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]
^ 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 .
PMC
9850942 .
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 .
PMC
6180102 .
PMID
30305615 .
^ Wang Y, Jiang SW, Liu X, Niu L, Ge XL, Zhang JC, et al. (2018).
"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 .
PMC
6312622 .
PMID
30662583 .
^ Hui L, Soliman ML, Geiger NH, Miller NM, Afghah Z, Lakpa KL, et al. (2019).
"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 .
TRPA
Activators
4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ12,14 -prostaglandin J2
α-Sanshool (
ginger ,
Sichuan and
melegueta peppers )
Acrolein
Allicin (
garlic )
Allyl isothiocyanate (
mustard ,
radish ,
horseradish ,
wasabi )
AM404
ASP-7663
Bradykinin
Cannabichromene (
cannabis )
Cannabidiol (
cannabis )
Cannabigerol (
cannabis )
Cinnamaldehyde (
cinnamon )
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (
cumin )
Curcumin (
turmeric )
Dehydroligustilide (
celery )
Diallyl disulfide
Dicentrine (
Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (
ginger )
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (
celery ,
Angelica acutiloba )
Linalool (
Sichuan pepper ,
thyme )
Methylglyoxal
Methyl salicylate (
wintergreen )
N-Methylmaleimide
Nicotine (
tobacco )
Oleocanthal (
olive oil )
Paclitaxel (
Pacific yew )
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (
Dorrigo pepper )
Shogaols (
ginger ,
Sichuan and
melegueta peppers )
Tear gases
Tetrahydrocannabinol (
cannabis )
Tetrahydrocannabiorcol
Thiopropanal S-oxide (
onion )
Umbellulone (Umbellularia californica )
WIN 55,212-2
Blockers
TRPC
TRPM
TRPML
TRPP
TRPV
Activators
2-APB
5',6'-EET
9-HODE
9-oxoODE
12S-HETE
12S-HpETE
13-HODE
13-oxoODE
20-HETE
α-Sanshool (
ginger ,
Sichuan and
melegueta peppers )
Allicin (
garlic )
AM404
Anandamide
Bisandrographolide (
Andrographis paniculata )
Camphor (
camphor laurel ,
rosemary ,
camphorweed ,
African blue basil ,
camphor basil )
Cannabidiol (
cannabis )
Cannabidivarin (
cannabis )
Capsaicin (
chili pepper )
Carvacrol (
oregano ,
thyme ,
pepperwort ,
wild bergamot , others)
DHEA
Diacyl glycerol
Dihydrocapsaicin (
chili pepper )
Estradiol
Eugenol (
basil ,
clove )
Evodiamine (
Euodia ruticarpa )
Gingerols (
ginger )
GSK1016790A
Heat
Hepoxilin A3
Hepoxilin B3
Homocapsaicin (
chili pepper )
Homodihydrocapsaicin (
chili pepper )
Incensole (
incense )
Lysophosphatidic acid
Low
pH (acidic conditions)
Menthol (
mint )
N-Arachidonoyl dopamine
N-Oleoyldopamine
N-Oleoylethanolamide
Nonivamide (PAVA) (
PAVA spray )
Nordihydrocapsaicin (
chili pepper )
Paclitaxel (
Pacific yew )
Paracetamol (acetaminophen)
Phenylacetylrinvanil
Phorbol esters (e.g.,
4α-PDD )
Piperine (
black pepper ,
long pepper )
Polygodial (
Dorrigo pepper )
Probenecid
Protons
RhTx
Rutamarin (
Ruta graveolens )
Resiniferatoxin (RTX) (
Euphorbia resinifera /
pooissonii )
Shogaols (
ginger ,
Sichuan and
melegueta peppers )
Tetrahydrocannabivarin (
cannabis )
Thymol (
thyme ,
oregano )
Tinyatoxin (
Euphorbia resinifera /
pooissonii )
Tramadol
Vanillin (
vanilla )
Zucapsaicin
Blockers