ML-SI3
目录号 : GC67784ML-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。
Cas No.:891016-02-7
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
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]。
| 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: | |
| Cas No. | 891016-02-7 | SDF | Download SDF |
| 分子式 | C23H31N3O3S | 分子量 | 429.58 |
| 溶解度 | DMSO : 50 mg/mL (116.39 mM; Need ultrasonic) | 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。 |
||
| 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。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3279 mL | 11.6393 mL | 23.2786 mL |
| 5 mM | 465.6 μL | 2.3279 mL | 4.6557 mL |
| 10 mM | 232.8 μL | 1.1639 mL | 2.3279 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet