ML SA1是一种选择性的TRPML激动剂，EC50值为15.3μM。
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.
ML SA1是一种选择性的TRPML激动剂，EC50值为15.3μM[1]。ML SA1表现出显著的抗病毒活性，能显著抑制登革热病毒(DENV)和寨卡病毒(ZIKV)的RNA，IC50值分别为8.93μM和52.99μM[2]。ML SA1通过下调TRPML2和TRPML3的表达、负调控晚期内体标志物Rab7的表达，并促进囊泡从晚期内体向溶酶体的转运，从而抑制病毒感染[3]。ML SA1已被广泛用于挽救阿尔茨海默病相关的内体-自噬-溶酶体系统改变[4]。
在体外，30μM的ML SA1处理NRK-52E细胞24小时，显著增加了LC3-II的表达并促进了细胞自噬[1]。25μM的ML SA1处理 HEK293T细胞18小时，显著减少了α-突触核蛋白聚集体及其蛋白水平[5]。10μM的ML SA1预处理小鼠海马神经元细胞1小时，显著降低了氧糖剥夺(OGD)诱导的cleaved caspase-3产生，并减少了神经元凋亡率[6]。
在体内，在视网膜脱离(RD)大鼠模型中，通过视网膜下腔单次注射10μM（5μl）的ML SA1，显著改善了视网膜结构和外核层，并减少了感光细胞的凋亡[8]。
| 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 | |
| 别名 | 2-[2-氧代-2-(2,2,4-三甲基-3,4-二氢-2H-喹啉-1-基)-乙基]-异吲哚-1,3-二酮 | ||
| 化学名 | (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 | ||
| 分子式 | C22H22N2O3 | 分子量 | 362.42 |
| 溶解度 | <7.25mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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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 |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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