ML SA1 (Synonyms: Mucolipin synthetic agonist 1) |
Catalog No.GC16850
One-Click Copy Product Info
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ML SA1 is a selective TRPML agonist with an EC50 value of 15.3μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 332382-54-4
Sample solution is provided at 25 µL, 10mM.
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ML SA1 is a selective TRPML agonist with an EC50 value of 15.3μM [1]. The ML SA1 exhibits remarkable antiviral activity, significantly inhibiting the RNA of dengue virus (DENV) and zika virus (ZIKV), with IC50 values of 8.93μM and 52.99μM, respectively[2]. ML SA1 inhibits viral infection by down-regulating the expression of TRPML2 and TRPML3, negatively regulating the expression of the late endosome marker Rab7, and promoting the transport of vesicles from the late endosome to the lysosome[3]. The ML SA1 has been widely used to rescue Alzheimer-related alterations of the endosomal-autophagic-lysosomal system [4].
In vitro, ML SA1 treatment (30μM) for 24 hours significantly increased the expression of LC3-II in NRK-52E cells and promoted autophagy of the cells[5]. Treatment with 25μM ML SA1 for 18 hours significantly reduced the α-synuclein aggregates and protein levels in HEK293T cells[6]. 10μM of ML SA1 pretreatment for 1 hour significantly reduced the production of cleaved caspase-3 in mouse hippocampal neuronal cells induced by oxygen-glucose deprivation (OGD), and decreased the apoptosis rate of neurons[7].
In vivo, ML SA1 treatment via subretinal space injection at a single dose 10μM (5μl) significantly improved retinal structure and the outer nuclear layer, and reduced the apoptosis of photoreceptor cells in a rat model of retinal detachment (RD) [8].
References:
[1] Cunha M R, Do Amaral B S, Takarada J E, et al. (S)‐ML‐SA1 Activates Autophagy via TRPML1‐TFEB Pathway[J]. Chembiochem, 2024, 25(22): e202400506.
[2] Xia Z, Wang L, Li S, et al. ML-SA1, a selective TRPML agonist, inhibits DENV2 and ZIKV by promoting lysosomal acidification and protease activity[J]. Antiviral Research, 2020, 182: 104922.
[3] Xia Z, Ren Y, Li S, et al. ML-SA1 and SN-2 inhibit endocytosed viruses through regulating TRPML channel expression and activity[J]. Antiviral Research, 2021, 195: 105193.
[4] Somogyi A, Kirkham E D, Lloyd-Evans E, et al. The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system[J]. Journal of cell science, 2023, 136(6): jcs259875.
[5] Miyano T, Sera T, Sakamoto N. Pharmacological activation of TRPML1 enhances autophagy regulating hypertonicity and TGF-β-induced EMT in proximal tubular epithelial cells[J]. Biochemical and Biophysical Research Communications, 2025, 750: 151432.
[6] Pollmanns M R, Beer J, Rosignol I, et al. Activated endolysosomal cation channel TRPML1 facilitates maturation of α-synuclein-containing autophagosomes[J]. Frontiers in cellular neuroscience, 2022, 16: 861202.
[7] Wang Y, Jiang S, Liu X, et al. Degradation of TRPML1 in neurons reduces neuron survival in transient global cerebral ischemia[J]. Oxidative Medicine and Cellular Longevity, 2018, 2018(1): 4612727.
[8] Yan Y, Wang Y, Ding J, et al. TRPML1 inhibited photoreceptor apoptosis and protected the retina by activation of autophagy in experimental retinal detachment[J]. Ophthalmic research, 2021, 64(4): 587-594.
| Cell experiment [1]: | |
Cell lines | NRK-52E cells |
Preparation Method | NRK-52E cells were grown in DMEM medium with 10% (v/v) fetal bovine serum (FBS), 0.2mM glutamine, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C in 5% CO2/atmosphere. Cells (2×105 cells/ml) were seeded onto 24-well plates allowed to adhere in a 5% CO2 incubator at 37°C overnight. Cells were treated with different concentrations of ML SA1 (0, 3, 10, and 30µM) for 24h. The expression of autophagy marker LC3-II was evaluated. |
Reaction Conditions | 0, 3, 10, and 30µM; 24h |
Applications | ML SA1 treatment significantly enhanced the LC3-II levels in NRK-52E cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Male Sprague-Dawley rats (250-300g) were housed singly in a standard environment with food and water ad libitum. The rats were anaesthetized by intraperitoneal injection of chloral hydrate 10%; 0.3ml/100g), and 0.5% tropicamide drops were used to dilate the pupils. Then, the eye surface was anaesthetized with 0.5% hydrochloride, and the conjunctival sac was rinsed using levofloxacin before the surgery. A 30-G needle was inserted into the subretinal space at a 45° angle from 2mm behind the limbus of the cornea through the sclera and vitreous cavity, and 50μl of 10% sodium hyaluronate was injected into the subretinal space to establish the RD model. For each animal, the right eye was used to develop the RD model, and the left eye served as a normal control. Any animal that experienced surgical complications was excluded from the study. After the RD model was established, a microinjector was used to carry out injections. ML SA1 was diluted in DMSO, and DMSO (5μl; 0.1%) and ML SA1 (5μl; 10μM) were gently injected into the subretinal space of RD model rats in the DMSO group and ML SA1 group, respectively. |
Dosage form | 10µM (5µl) for once; subretinal space injection |
Applications | ML SA1 treatment significantly improved retinal structure and the outer nuclear layer, and reduced the apoptosis of photoreceptor cells in RD rats. |
References: | |
| Cas No. | 332382-54-4 | SDF | |
| Synonyms | Mucolipin synthetic agonist 1 | ||
| Chemical Name | (R)-2-(2-oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl)ethyl)isoindoline-1,3-dione | ||
| Canonical SMILES | O=C(CN(C1=O)C(C2=CC=CC=C12)=O)N3C(C)(C)C[C@@H](C)C4=CC=CC=C34 | ||
| Formula | C22H22N2O3 | M.Wt | 362.42 |
| Solubility | <7.25mg/ml in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7592 mL | 13.7961 mL | 27.5923 mL |
| 5 mM | 551.8 μL | 2.7592 mL | 5.5185 mL |
| 10 mM | 275.9 μL | 1.3796 mL | 2.7592 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)