WAY-204688 (SIM-688)
(Synonyms: SIM-688) 目录号 : GC31798
WAY-204688 (SIM-688) 是一种雌激素受体 (ER-α) 选择性、口服活性的 NF-κB 转录活性抑制剂，IC50 为 122±30 nM 作用于 NF-κB-荧光素酶κB-luc) 在 HAECT-1 细胞中。
Cas No.:796854-35-8
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
WAY-204688 is an estrogen receptor (ER-α) selective, orally active inhibitor of NF-κB transcriptional activity with an IC50 of 122 ± 30 nM for NF-κB-luciferase (NF-κB-luc) in HAECT-1 cells.
WAY-204688 is ER-dependenrt (activity seen only when hER is coexpressed with NF-κB-luciferase in human aortic endothelial cell lines (HAECT-1) cells). The interaction of WAY-204688 with ERα and ERβ is examined in vitro. WAY-204688 displaces [3H]E2 from the ERα ligand binding domain protein (LBD) with IC50=2.43 μM and from the ERβ ligand binding domain protein (LBD) with IC50=1.5 μM[1].
WAY-204688 (5 mg/kg per day, po daily for 5 weeks) is evaluated in vivo for the ability to inhibit four proinflammatory genes (MHC, invariant chain (MHI), VCAM-1, RANTES, and TNF-α). The effect of WAY-204688 on induction of the gene products and on uterine wet weight is compared to that of 17α-ethinyl 17β-estradiol (EE at 10 μg/kg per day) in the same paradigm. Further characterization of WAY-204688 is carried out in several preclinical models of inflammatory disease. In the Lewis rat adjuvant-induced arthritis model (AIA), WAY-204688 is active at a dose of 0.3 mg/kg per day, po[1].
[1]. Caggiano TJ, et al. Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment for rheumatoid arthritis. J Med Chem. 2007 Nov 1;50(22):5245-8.
| Cas No. | 796854-35-8 | SDF | |
| 别名 | SIM-688 | ||
| Canonical SMILES | COC1=C([C@H](C2=CC=CC3=C2C=CC=C3)[C@@](C)(C#N)C(N4CCC(C5=CC(C(F)(F)F)=CC=C5)CC4)=O)C=CC=C1 | ||
| 分子式 | C34H31F3N2O2 | 分子量 | 556.62 |
| 溶解度 | DMSO : 100 mg/mL (179.66 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 | 1.7966 mL | 8.9828 mL | 17.9656 mL |
| 5 mM | 0.3593 mL | 1.7966 mL | 3.5931 mL |
| 10 mM | 0.1797 mL | 0.8983 mL | 1.7966 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 activity of pathway-selective estrogen receptor ligands in experimental septic shock
Estrogen receptors (ER) are widely expressed in multiple genital and nongenital tissues. Upon engagement of these receptors, multiple genes are affected in target tissues via estrogen response elements. Nonsteroidal pathway-selective ER ligands have recently been identified that inhibit NF-kappaB transcriptional activity and are devoid of conventional estrogenic activities on genital tissues. These pathway-selective ligands are potent anti-inflammatory agents in vivo and may prove to be of therapeutic utility in systemic inflammatory states. These pathway-selective ER ligands were tested in the murine listeriosis model, the neutropenic rat model, and the mouse cecal ligation and puncture model. WAY-204688 did not have any significant activity after systemic infection by Listeria monocytogenes. In the neutropenic rat model, WAY-204688 provided a significant survival benefit against an otherwise lethal challenge of Pseudomonas aeruginosa 12.4.4 compared with the control group (88% versus 25% survival; P < 0.05). Preservation of mucosal weight and prevention of histopathologic changes were observed with the administration of WAY-204688. Similar findings were observed in a cecal ligation and puncture model with WAY-204688 and a related compound WAY-169916. These results indicate that oral administration of these pathway-selective ER ligands preserved gastrointestinal barrier function and improve outcome in experimental models of systemic infection and inflammation. These agents may prove to be useful clinically as a novel treatment strategy for severe sepsis.
Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment for rheumatoid arthritis
Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF-kappaB. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional estrogens.