GlpBio

ML-SI3

目录号: GC67784纯度: >99.00%
ML-SI3是一种阳离子通道TRPML抑制剂，对TRPML1和TRPML2的IC50值分别为4.7μM和1.7μM。
ML-SI3
Cas No.: 891016-02-7
规格价格库存数量操作
1mg¥597.00现货
1
2mg¥878.00现货
1
5mg¥1,470.00现货
1
10mg¥2,310.00现货
1
25mg¥3,890.00现货
1
50mg¥5,580.00现货
1
100mg¥7,820.00现货
1
10mM (in 1mL DMSO)¥1,630.00现货
1
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产品描述 Description

ML-SI3 is cation channel TRPML inhibitor, with IC50 values of 4.7μM and 1.7μM for TRPML1 and TRPML2, respectively [1]. ML-SI3 binds to the hydrophobic cavity created by S5, S6, and PH1, blocking channel activation of TRPML1 without inhibiting PI(3,5)P2-dependent activation of the channel [2]. ML-SI3 has been widely used to stimulate the secretion of protons by human gastric epithelial cell lines[3].

In vitro, ML-SI3 treatment at 20μM for 24 hours significantly promoted the apoptosis of rat hippocampal neuronal cells and disrupted mitochondrial function[4]. The 75µM ML-SI3 treatment for 24 hours significantly disrupted the epidermal integrity of adult schistosomes[5]. The 24-hour treatment with 10µM ML-SI3 antagonized the peripheral localization of lysosome-associated membrane protein 1 (LAMP1) and fibronectin 1 (FN1) induced by Inositol polyphosphate 4-phosphatase, type II (INPP4B) in BxPC-3 cells[6].

In vivo, ML-SI3 treatment via intraperitoneal injection at a dose of 1.5mg/kg every 2 days for 28 days can protect the myocardial ischemia/reperfusion injury in mice by restoring the autophagy of damaged myocardial cells[7]. ML-SI3 treatment (16mg/kg/day; i.p.) for 3 weeks significantly reversed the inhibitory effect of ML-SA5 (2mg/kg; i.p.) on the lung metastasis of melanoma in mouse model of melanoma[8].

References:
[1] Rühl P, Rosato A S, Urban N, et al. Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors[J]. Scientific reports, 2021, 11(1): 8313.
[2] Schmiege P, Fine M, Li X. Atomic insights into ML-SI3 mediated human TRPML1 inhibition[J]. Structure, 2021, 29(11): 1295-1302. e3.
[3] Mueller A U, Andersen G, Richter P, et al. Activation of the TRPML1 Ion Channel Induces Proton Secretion in the Human Gastric Parietal Cell Line HGT-1[J]. International Journal of Molecular Sciences, 2024, 25(16): 8829.
[4] Peng T, Xie Y, Zhao S, et al. TRPML1 ameliorates seizures-related neuronal injury by regulating autophagy and lysosomal biogenesis via Ca2+/TFEB signaling pathway[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2024, 1870(8): 167477.
[5] Bais S, Norwillo A, Ruthel G, et al. Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity[J]. Biochimie, 2022, 194: 108-117.
[6] Saffi G T, Kleine N, Salmena L. The lipid phosphatase INPP4B controls pancreatic cancer cell migration and invasion by regulating fibronectin exocytosis[J]. Journal of Biological Chemistry, 2025: 110716.
[7] Xing Y, Sui Z, Liu Y, et al. Blunting TRPML1 channels protects myocardial ischemia/reperfusion injury by restoring impaired cardiomyocyte autophagy[J]. Basic research in cardiology, 2022, 117(1): 20.
[8] Xing Y, Wei X, Liu Y, et al. Autophagy inhibition mediated by MCOLN1/TRPML1 suppresses cancer metastasis via regulating a ROS-driven TP53/p53 pathway[J]. Autophagy, 2022, 18(8): 1932-1954.

ML-SI3是一种阳离子通道TRPML抑制剂，对TRPML1和TRPML2的IC50值分别为4.7μM和1.7μM[1]。ML-SI3通过结合由S5、S6和PH1结构域形成的疏水空腔，阻断TRPML1的通道激活，且不抑制PI(3,5)P2依赖的通道活化[2]。ML-SI3已广泛应用于刺激人胃上皮细胞系的质子分泌[3]。

在体外，使用20μM的ML-SI3处理大鼠海马神经元细胞24小时，能显著促进细胞凋亡并破坏线粒体功能[4]。用75µM的ML-SI3处理成年血吸虫24小时，可显著破坏表皮完整性[5]。以10µM的ML-SI3处理BxPC-3细胞24小时，能拮抗Inositol polyphosphate 4-phosphatase, type II(INPP4B)诱导的溶酶体相关膜蛋白1(LAMP1)和纤连蛋白1(FN1)的外周定位[6]。

在体内，每两天腹腔注射1.5mg/kg剂量的ML-SI3连续28天，可通过恢复受损心肌细胞的自噬保护小鼠心肌缺血/再灌注损伤[7]。每日腹腔注射16mg/kg剂量的ML-SI3连续3周，可显著逆转ML-SA5（2mg/kg; i.p.）在黑色素瘤小鼠模型中对黑素瘤肺转移的抑制作用[8]。

实验参考方法 Experimental Reference Method

Cell experiment [1]:

Cell lines

Rat hippocampal neuronal cells

Preparation Method

The rat hippocampal neuronal cells were cultured in a growth medium, which consisted of 10% fetal bovine serum (FBS), 1% penicillin-streptomycin solution, 1% glutamine, and 88% neural basal medium. The cells were seeded at an appropriate density on the culture plates. After the initial culture for 4-6 hours, the growth medium was replaced with a maintenance medium, which consisted of 2% B27, 1% penicillin-streptomycin solution, 1% glutamine, and 96% neural basal medium. The maintenance medium was changed every 2-3 days. On the 10th day of culture, the cultured neurons were randomly divided into five groups: (1) CON group (cultured in an environment containing Mg2+), (2) Mg2+-free group (exposed to an environment without Mg2+), (3) DMSO group (pre-treated with DMSO for 24 hours before exposure to the Mg2+-free environment), (4) ML-SA1 group (pre-treated with 20μM ML-SA1 for 24 hours before exposure to the Mg2+-free environment), and (5) ML-SI3 group (pre-treated with 20μM ML-SI3 for 24 hours before exposure to the Mg2+-free environment). The survival of the nerve cells was analyzed.

Reaction Conditions

20μM; 24h

Applications

ML-SI3 treatment suppressed viability of nerve cells and aggravated apoptosis.
Animal experiment [2]:

Animal models

BALB/c nude mouse

Preparation Method

Resuspend 0.5×106 A-375-luc cells to a final volume of 200µl, and then slowly inject them into the tail of approximately 6-week-old BALB/c nude mice. Divide the mice into three groups. Administer intraperitoneal injections of PBS, ML-SA5 (2mg/kg), or ML-SA5 (2mg/kg)+ML-SI3 (16mg/kg) every day for three weeks. Then, 10 minutes before imaging, inject 0.2ml of D-fluorescein (30mg/ml) into the mice's abdominal cavity. Monitor bioluminescence weekly to identify melanoma metastasis.

Dosage form

16mg/kg/day for 3 weeks; i.p.

Applications

ML-SI3 treatment significantly reversed the inhibitory effect of ML-SA5 on the lung metastasis of melanoma in mice.

References:
[1] Peng T, Xie Y, Zhao S, et al. TRPML1 ameliorates seizures-related neuronal injury by regulating autophagy and lysosomal biogenesis via Ca2+/TFEB signaling pathway[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2024, 1870(8): 167477.
[2] Xing Y, Wei X, Liu Y, et al. Autophagy inhibition mediated by MCOLN1/TRPML1 suppresses cancer metastasis via regulating a ROS-driven TP53/p53 pathway[J]. Autophagy, 2022, 18(8): 1932-1954.

产品文档 Product Documents

Purity:>99.00%

化学性质Chemical Properties

CAS 号
891016-02-7
分子式
C23H31N3O3S
分子量
429.58 g/mol
溶解性
DMSO : 50 mg/mL (116.39 mM; Need ultrasonic)
保存条件
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°C，然后在超声波浴中震荡一段时间。
Shipping Condition
评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备 RT，或根据请求配备蓝冰。

计算工具摩尔浓度 / 稀释 / 分子量 / 单位换算 / 体内配方 / 溶解度

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