MDL 28170
(Synonyms: Calpain Inhibitor III) 目录号 : GC11640
MDL 28170是一种细胞渗透性、可逆的肽醛类抑制剂，可抑制钙蛋白酶（Ki=0.01µM；对组织蛋白酶B的Ki=0.025µM）。
Cas No.:88191-84-8
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');)
MDL 28170, a cell permeable, reversible, peptidic aldehyde inhibitor of calpain (Ki= 0.01µM; Ki for cathepsin B = 0.025µM)[1]. MDL 28170 caused the death of Leishmania amazonensis with an IC50 value of 15µM and triggered depolarization of mitochondrial membranes[2]. MDL 28170 has been used as a neuroprotective agent in many rodent models of neurotrauma, including spinal cord injury, neonatal hypoxic-ischemia, and focal cerebral ischemia, and has reduced neuronal loss and improved motor function in mouse models of Parkinson's disease [3].
In vitro, MDL 28170 treatment at 50μM for 30min prevented Aβ25-35-induced cell death and increased cell survival in SH-SY5Y cells[4]. MDL 28170 treatment (2.5μM; 72h) reduced high glucose-induced cell death, reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, and normalized reactive oxygen species[5].
In vivo, MDL 281709 treatment via intraperitoneal injection at 10mg/kg/day for 14 days can improve nociception and behavioral deficits in diabetic neuropathy, reduce calpain activity, oxidative stress, and neuroinflammation in diabetic neuropathy, and improve neurological function parameters in diabetic rats[6]. A single rapid injection of MDL 28170 at 30mg/kg in the tail vein of Wistar rats 30min before traumatic brain injury (TBI) significantly reduced the mean number of damaged axons in the analyzed brainstem fiber bundles[7]. A single dose of MDL 28170 (1.0μL; 50000µM; i.c.) in the acute phase of TBI within rats during 7 days can improve the brain microenvironment by inhibiting inflammation, promoting the survival of transplanted GFP-bone marrow-derived mesenchymal stem cells (BMSCs), reducing the apoptosis of transplanted cells, and decreasing the lesion cavity[8].
References:
[1] Saatman K E, Creed J, Raghupathi R. Calpain as a therapeutic target in traumatic brain injury[J]. Neurotherapeutics, 2010, 7(1): 31-42.
[2] Marinho F A, Gonçalves K C S, Oliveira S S C, et al. The calpain inhibitor MDL28170 induces the expression of apoptotic markers in Leishmania amazonensis promastigotes[J]. PLoS One, 2014, 9(1): e87659.
[3] Thompson S N, Carrico K M, Mustafa A G, et al. A pharmacological analysis of the neuroprotective efficacy of the brain-and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model[J]. Journal of neurotrauma, 2010, 27(12): 2233-2243.
[4] Seyb K I, Schuman E R, Ni J, et al. Identification of small molecule inhibitors of β-amyloid cytotoxicity through a cell-based high-throughput screening platform[J]. Journal of biomolecular screening, 2008, 13(9): 870-878.
[5] Ong S B, Lee W H, Shao N Y, et al. Calpain inhibition restores autophagy and prevents mitochondrial fragmentation in a human iPSC model of diabetic endotheliopathy[J]. Stem cell reports, 2019, 12(3): 597-610.
[6] Kharatmal S B, Singh J N, Sharma S S. Calpain inhibitor, MDL 28170 confer electrophysiological, nociceptive and biochemical improvement in diabetic neuropathy[J]. Neuropharmacology, 2015, 97: 113-121.
[7]Buki A, Farkas O, Doczi T, et al. Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury[J]. Journal of neurotrauma, 2003, 20(3): 261-268.
[8] Hu J, Chen L, Huang X, et al. Calpain inhibitor MDL28170 improves the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells following traumatic brain injury[J]. Stem cell research & therapy, 2019, 10(1): 96.
MDL 28170是一种细胞渗透性、可逆的肽醛类抑制剂，可抑制钙蛋白酶（Ki=0.01µM；对组织蛋白酶B的Ki=0.025µM）。MDL 28170能诱导亚马逊利什曼原虫死亡（IC50=15µM），并引发线粒体膜去极化[2]。MDL 28170在多种神经创伤啮齿类模型（包括脊髓损伤、新生儿缺氧缺血和局灶性脑缺血）中作为神经保护剂应用，并在帕金森病小鼠模型中减少神经元丢失、改善运动功能[3]。
在体外，50μM的MDL 28170处理30分钟可抑制Aβ25-35诱导的SH-SY5Y细胞死亡并提高细胞存活率[4]。MDL 28170 （2.5μM； 72小时）处理原代人主动脉内皮细胞减少了高糖诱导的细胞死亡，减少了线粒体碎片，同时维持了ATP的生成，并使活性氧水平正常化[5]。
在体内，糖尿病神经病变大鼠经腹腔注射MDL 28170（10mg/kg/day）14天可改善痛觉和行为缺陷，降低钙蛋白酶活性、氧化应激和神经炎症，并改善神经功能参数[6]。Wistar大鼠在创伤性脑损伤（TBI）前30分钟经尾静脉单次快速注射30mg/kg剂量的MDL 28170，显著减少脑干纤维束的轴突损伤数量[7]。TBI急性期大鼠单次给予MDL 28170（1.0μL, 50000µM; i.c.）治疗7天，可抑制炎症、提高移植GFP骨髓间充质干细胞（BMSC）存活率、减少移植细胞凋亡和缩小病变腔并改善脑微环境[8]。
| Cell experiment [1]: | |
Cell lines | Primary human aortic endothelial cells |
Preparation Method | Primary human aortic endothelial cells were seeded on 0.2% gelatin-coated plates in EGM-2 medium for 24h. For hyperglycemic conditions, plating medium was then exchanged into a modified EGM-2 medium containing 33mM glucose and 10nM endothelin-1, and cultured for 72h. MDL 28170 was used at a final concentration of 2.5μM (72h). Following treatment of cells under hyperglycemic conditions with or without MDL 28170, 100µl of CellTiter-Glo reagent was added directly to each well of 96-well plates, followed by incubation at room temperature on an orbital shaker to induce cell lysis for 12 minutes. For assessing intracellular ROS generation, six hours prior to the completion of treatment the H2O2 substrate was added and incubated for the final 6 hours of the experiment. 50µl of media samples were transferred to a separate 96-well white-sided plate and 50µl of ROS Detection Solution was added to each well, followed by incubation at room temperature for 20 minutes before detecting luminescence signal. Cells in the original sample plate were kept for measuring total cell number by Calcein-AM to allow normalization. |
Reaction Conditions | 2.5μM; 72h |
Applications | MDL 28170 treatment reduced high glucose-induced cell death and normalized reactive oxygen species levels in primary human aortic endothelial cells. |
| Animal experiment [2]: | |
Animal models | C57BL6 mice |
Preparation Method | Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50mg/kg) in citrate buffer (pH 4.5). Age-matched (12-15 weeks; weighing 250-275g) male Sprague-Dawley rats in the control group received a vehicle injection. Blood glucose levels in the tail vein were measured 48h after STZ administration, and blood glucose levels higher than 250mg/dl were defined as the occurrence of diabetes. After the sixth week of diabetes induction, diabetic rats were given an intraperitoneal injection of MDL 28170 at a dose of 10mg/kg/day for 14 days. Parametric studies (motor nerve conduction velocity and nerve blood flow) and behavioral studies (thermal hyperalgesia and mechanical allodynia) were performed. |
Dosage form | 10mg/kg/day for 14 days; i.p. |
Applications | MDL 281709 treatment can improve nociception and behavioral deficits in diabetic neuropathy, reduce calpain activity, oxidative stress, and neuroinflammation in diabetic neuropathy, and improve neurological function parameters in diabetic rats. |
References: | |
| Cas No. | 88191-84-8 | SDF | |
| 别名 | Calpain Inhibitor III | ||
| 化学名 | benzyl N-[(2S)-3-methyl-1-oxo-1-[(1-oxo-3-phenylpropan-2-yl)amino]butan-2-yl]carbamate | ||
| Canonical SMILES | CC(C)C(C(=O)NC(CC1=CC=CC=C1)C=O)NC(=O)OCC2=CC=CC=C2 | ||
| 分子式 | C22H26N2O4 | 分子量 | 382.45 |
| 溶解度 | ≥ 16.75mg/mL in DMSO, ≥ 25.05 mg/mL in EtOH with 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 | 2.6147 mL | 13.0736 mL | 26.1472 mL |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 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: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet