LDC7559
目录号 : GC65393
LDC7559 is a potent Gasdermin D(GSDMD) inhibitor inhibiting the pyroptosis and lessens its inflammation.
Cas No.:2407782-01-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LDC7559 is a potent Gasdermin D(GSDMD) inhibitor inhibiting the pyroptosis and lessens its inflammation.
[1] Pandeya A, et al. Medchemcomm. 2019 Apr 4;10(5):660-667
| Cas No. | 2407782-01-6 | SDF | Download SDF |
| 分子式 | C20H19N3O3 | 分子量 | 349.38 |
| 溶解度 | DMSO : ≥ 125 mg/mL (357.78 mM) | 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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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8622 mL | 14.3111 mL | 28.6221 mL |
| 5 mM | 0.5724 mL | 2.8622 mL | 5.7244 mL |
| 10 mM | 0.2862 mL | 1.4311 mL | 2.8622 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。
Selective activation of PFKL suppresses the phagocytic oxidative burst
Cell 2021 Aug 19;184(17):4480-4494.e15.PMID:34320407DOI:10.1016/j.cell.2021.07.004.
In neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) generated via the pentose phosphate pathway fuels NADPH oxidase NOX2 to produce reactive oxygen species for killing invading pathogens. However, excessive NOX2 activity can exacerbate inflammation, as in acute respiratory distress syndrome (ARDS). Here, we use two unbiased chemical proteomic strategies to show that small-molecule LDC7559, or a more potent designed analog NA-11, inhibits the NOX2-dependent oxidative burst in neutrophils by activating the glycolytic enzyme phosphofructokinase-1 liver type (PFKL) and dampening flux through the pentose phosphate pathway. Accordingly, neutrophils treated with NA-11 had reduced NOX2-dependent outputs, including neutrophil cell death (NETosis) and tissue damage. A high-resolution structure of PFKL confirmed binding of NA-11 to the AMP/ADP allosteric activation site and explained why NA-11 failed to agonize phosphofructokinase-1 platelet type (PFKP) or muscle type (PFKM). Thus, NA-11 represents a tool for selective activation of PFKL, the main phosphofructokinase-1 isoform expressed in immune cells.
LDC7559 Exerts Neuroprotective Effects by Inhibiting GSDMD-Dependent Pyroptosis of Microglia in Mice with Traumatic Brain Injury
J Neurotrauma 2023 Apr;40(7-8):742-757.PMID:35920115DOI:10.1089/neu.2021.0318.
Abstract Pyroptosis is considered one of a critical factor in the recovery of neurological function following traumatic brain injury. Brain injury activates a molecular signaling cascade associated with pyroptosis and inflammation, including NLRP3, inflammatory cytokines, caspase-1, gasdermin D (GSDMD), and other pyroptosis-related proteins. In this study, we explored the neuroprotective effects of LDC7559, a GSDMD inhibitor. Briefly, LDC7559, siRNA-GSDMD (si-GSDMD), or equal solvent was administrated to mice with a lipopolysaccharide + nigericin (LPS + Nig) model in vitro or with controlled cortical impact brain injury. The findings revealed that inflammation and pyroptosis levels were decreased by LDC7559 or si-GSDMD treatment both in vitro and in vivo. Immunofluorescence staining, brain water content, hematoxylin and eosin staining, and behavioral investigations suggested that LDC7559 or si-GSDMD inhibited microglial proliferation, ameliorated cerebral edema, reduced brain tissue loss, and promoted brain function recovery. Taken together, LDC7559 may inhibit pyroptosis and reduce inflammation by inhibiting GSDMD, thereby promoting the recovery of neurological function.