BC-1382
目录号 : GC68150BC-1382 是一种有效的泛素 E3 连接酶 HECTD2 抑制剂，可特异性破坏 HECTD2/PIAS1 相互作用 (IC50≈ 5 nM)。具有抗炎活性。
Cas No.:1013753-99-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BC-1382 is a potent ubiquitin E3 ligase HECTD2 inhibitor that specificly disrupts the HECTD2/PIAS1 interaction (IC50≈ 5 nM).Anti-inflammatory activity[1].
BC-1382 targets HECTD2 and attenuates lipopolysaccharide (LPS)- and Pseudomonas aeruginosa-induced lung inflammation. HECTD2 is an ubiquitin E3 ligase. BC-1382 reduces the severity of cytokine-driven lung inflammation[1].
BC-1382 drastically increases PIAS1 protein level in a nonstimulus condition with IC50≈100 nM[1].
BC-1382 improves PIAS1 protein stability by increasing its t1/2[1].
BC-1382 suppresses LPS-induced PIAS1 degradation and restores PIAS1 protein levels at 800 nM[1].
BC-1382 suppresses LPS-induced proinflammatory cytokines released by human peripheral blood mononuclear cells (PBMCs)[1].
BC-1382 (10 mg/kg; intraperitoneal injection) significantly decreases lavage protein concentrations, lavage cell counts, and cell infiltrates in both PA103-stimulated and LPS-stimulated mice. BC-1382 significantly decreases lavage cytokine levels in both models[1].
| Animal Model: | C57BL/6J mice were challenged intratracheally with PA103 (104 CFU per mouse) or LPS (3 mg/kg)[1] |
| Dosage: | 10 mg/kg |
| Administration: | Given through intraperitoneal injection |
| Result: | Significantly decreased lavage protein concentrations, lavage cell counts, and cell infiltrates in both PA103-stimulated and LPS-stimulated mice. Significantly decreased lavage cytokine levels in both models. |
[1]. Tiffany A Coon, et al. The proinflammatory role of HECTD2 in innate immunity and experimental lung injury. Sci Transl Med. 2015 Jul 8;7(295):295ra109.
| Cas No. | 1013753-99-5 | SDF | Download SDF |
| 分子式 | C23H29N3O5S | 分子量 | 459.56 |
| 溶解度 | DMSO : 125 mg/mL (272.00 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。 |
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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 | 2.176 mL | 10.88 mL | 21.7599 mL |
| 5 mM | 0.4352 mL | 2.176 mL | 4.352 mL |
| 10 mM | 0.2176 mL | 1.088 mL | 2.176 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。
The proinflammatory role of HECTD2 in innate immunity and experimental lung injury
Sci Transl Med 2015 Jul 8;7(295):295ra109.PMID:26157031DOI:PMC4706383
Invading pathogens may trigger overactivation of the innate immune system, which results in the release of large amounts of proinflammatory cytokines (cytokine storm) and leads to the development of pulmonary edema, multiorgan failure, and shock. PIAS1 is a multifunctional and potent anti-inflammatory protein that negatively regulates several key inflammatory pathways such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor κB (NF-κB). We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. We also identified a mislocalized HECTD2 polymorphism, HECTD2(A19P), that was present in 8.5% of the population and functioned to reduce inflammation. This polymorphism prevented HECTD2/PIAS1 nuclear interaction, thus preventing PIAS1 degradation. The HECTD2(A19P) polymorphism was also protective toward acute respiratory distress syndrome (ARDS). We then developed a small-molecule inhibitor, BC-1382, that targeted HECTD2 and attenuated lipopolysaccharide (LPS)- and Pseudomonas aeruginosa-induced lung inflammation. These studies describe an unreported innate immune pathway and suggest that mutation or antagonism of the E3 ligase HECTD2 results in reduced severity of lung inflammation by selectively modulating the abundance of the anti-inflammatory protein PIAS1.