SI-109
目录号 : GC61275
SI-109是一种有效的STAT3SH2domain结构域抑制剂(Ki=9nM)，具有抗肿瘤活性。SI-109有效抑制STAT3的转录活性(IC50=3μM)。SI-109和CRBN类似物lenalidomide配体用于设计PROTACSTAT3降解剂SD-36。
Cas No.:2429877-30-3
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
SI-109 is a potent STAT3 SH2 domain inhibitor (Ki=9 nM) with antitumor activity. SI-109 effectively inhibits the transcriptional activity of STAT3 (IC50=3 μM). SI-109 and an analog of CRBN ligand lenalidomide have been used to design PROTAC STAT3 degrader SD-36[1].
SI-109 exerts a moderate growth inhibitory activity in MOLM-16 cells (IC50=3 μM)[1].SI-109 is ineffective in inhibition of STAT3 Y705 phosphorylation and in suppression of c-Myc expression at concentrations as high as 10 μM[1].
[1]. Bai L, et al. A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo. Cancer Cell. 2019 Nov 11;36(5):498-511.e17.
| Cas No. | 2429877-30-3 | SDF | |
| Canonical SMILES | O=C([C@@H](NC([C@@H]1CC[C@H](CCN(C(C)=O)C[C@@H]2NC(C3=CC(C=C(C(F)(P(O)(O)=O)F)C=C4)=C4N3)=O)N1C2=O)=O)CCC(N)=O)NC(C5=CC=CC=C5)C6=CC=CC=C6 | ||
| 分子式 | C40H44F2N7O9P | 分子量 | 835.79 |
| 溶解度 | DMSO: 150 mg/mL (179.47 mM) | 储存条件 | -20°C, stored under nitrogen |
| 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 | 1.1965 mL | 5.9824 mL | 11.9647 mL |
| 5 mM | 0.2393 mL | 1.1965 mL | 2.3929 mL |
| 10 mM | 0.1196 mL | 0.5982 mL | 1.1965 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。
Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein
J Med Chem 2019 Dec 26;62(24):11280-11300.PMID:31747516DOI:PMC8848307
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and an attractive therapeutic target for cancer and other human diseases. Despite 20 years of persistent research efforts, targeting STAT3 has been very challenging. We report herein the structure-based discovery of potent small-molecule STAT3 degraders based upon the proteolysis targeting chimera (PROTAC) concept. We first designed SI-109 as a potent, small-molecule inhibitor of the STAT3 SH2 domain. Employing ligands for cereblon/cullin 4A E3 ligase and SI-109, we obtained a series of potent PROTAC STAT3 degraders, exemplified by SD-36. SD-36 induces rapid STAT3 degradation at low nanomolar concentrations in cells and fails to degrade other STAT proteins. SD-36 achieves nanomolar cell growth inhibitory activity in leukemia and lymphoma cell lines with high levels of phosphorylated STAT3. A single dose of SD-36 results in complete STAT3 protein degradation in xenograft tumor tissue and normal mouse tissues. SD-36 achieves complete and long-lasting tumor regression in the Molm-16 xenograft tumor model at well-tolerated dose-schedules. SD-36 is a potent, selective, and efficacious STAT3 degrader.