SHP394
目录号 : GC65533
SHP394 是一种有效的，具有口服活性的，变构的选择性SHP2 抑制剂，IC50 为 23 nM。
Cas No.:2055757-40-7
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
SHP394 is an orally active, selective and allosteric inhibitor of SHP2, with an IC50 of 23 nM[1].
SHP394 inhibits Caco-2 cells proliferation with the IC50 of 297 nM[1].SHP394 exhibits antiproliferation activity against the Detroit-562 pharyngeal carcinoma cell line in vitro (IC50= 1.38 μM) [1].SHP394 decreases p-ERK with an IC50 of 18 nM KYSE520 cells[1].
SHP394 (20-80 mg/kg; oral gavage; twice daily) dose-dependent reduces tumor volume[1].SHP394 (80 mg/kg; oral gavage; twice daily) causes tumor 34% regression and reduces mouse host bodyweight after dosing for 14 days[1].
[1]. Sarver P, et al. 6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors. J Med Chem. 2019 Feb 28;62(4):1793-1802.
| Cas No. | 2055757-40-7 | SDF | Download SDF |
| 分子式 | C20H25F3N6O2S | 分子量 | 470.51 |
| 溶解度 | DMSO : 24 mg/mL (51.01 mM; Need ultrasonic) | 储存条件 | 4°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 | 2.1254 mL | 10.6268 mL | 21.2535 mL |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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。
6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors
J Med Chem 2019 Feb 28;62(4):1793-1802.PMID:30688459DOI:10.1021/acs.jmedchem.8b01726
Protein tyrosine phosphatase SHP2 is an oncoprotein associated with cancer as well as a potential immune modulator because of its role in the programmed cell death PD-L1/PD-1 pathway. In the preceding manuscript, we described the optimization of a fused, bicyclic screening hit for potency, selectivity, and physicochemical properties in order to further expand the chemical diversity of allosteric SHP2 inhibitors. In this manuscript, we describe the further expansion of our approach, morphing the fused, bicyclic system into a novel monocyclic pyrimidinone scaffold through our understanding of SAR and use of structure-based design. These studies led to the identification of SHP394 (1), an orally efficacious inhibitor of SHP2, with high lipophilic efficiency, improved potency, and enhanced pharmacokinetic properties. We also report other pyrimidinone analogues with favorable pharmacokinetic and potency profiles. Overall, this work improves upon our previously described allosteric inhibitors and exemplifies and extends the range of permissible chemical templates that inhibit SHP2 via the allosteric mechanism.