PRT-060318
(Synonyms: PRT318) 目录号 : GC11321
A potent and selective Syk inhibitor
Cas No.:1194961-19-7
Sample solution is provided at 25 µL, 10mM.
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IC50: 4 nM
PRT-060318 is a novel Syk inhibitor.
Heparin-induced thrombocytopenia is a heparin therapy complication in which IgG antibodies against the platelet factor 4-heparin complex activate platelets. The FcγRIIA clustering initiates signaling cascades involving tyrosine kinases, such as spleen tyrosine kinase (Syk).
In vitro: PRT-060318 was identified as a potent inhibitor of purified Syk kinase. Syk kinase was inhibited by 92%, while the activities all other kinases retained more than 70% when PRT-060318 were evaluated at a concentration of 50 nM in a broad panel of kinase enzyme assays. In addition, PRT-060318 could dose-responsively inhibited convulxin-induced human PRP aggregation. Moreover, it was found that PRT-060318 was able to dose-responsively inhibit the increases in intracellular calcium in convulxin-treated platelets [1].
In vivo: Animal study showed that in contrast to vehicle-treated mice developed the expected thrombocytopenia, PRT-060318-treated mice had no significant change in platelet counts after injection of heparin. Moreover, the nadir platelet counts of PRT-060318-treated mice were found to be significantly higher than control mice. The PRT-060318-treated mice showed no bleeding diathesis or other adverse effects. In addition, PRT-060318 treatment in crush thrombosis model resulted in significant inhibition of platelet deposition without changing bleeding time [1].
Clinical trial: Up to now, PRT-060318 is still in the preclinical development stage.
Reference:
[1] Reilly MP,Sinha U,André P,Taylor SM,Pak Y,Deguzman FR,Nanda N,Pandey A,Stolla M,Bergmeier W,McKenzie SE. PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model. Blood.2011 Feb 17;117(7):2241-6.
Cell experiment: | PRT318 is dissolved in DMSO. Cells are incubated for 14 days in 24-well plates. CLL cells are cultured under standardized conditions on NLC or in suspension, in the presence or absence of PRT318 and P505-15. At 24, 48, 72 h, CLL cells are collected and assayed for cell viability[2]. |
Animal experiment: | Mice: Heparin-induced thrombocytopenia (HIT) model mice are treated with KKO (20 mg/kg body weight, intraperitoneally) on day 0. The mice are divided into sex- and weight-matched experimental and control groups. On days 1 to 7, experimental mice (n=6) receives PRT318 (30 mg/kg body weight) orally via gavage twice a day, whereas control mice (n=6) receives vehicle only (sterile water). Both groups receives heparin (1600 U/kg body weight, subcutaneously) once daily. Mice are anesthetized by isoflurane inhalation for injections and blood collections[1]. |
References: [1]. Reilly MP, et al. PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model. Blood. 2011 Feb 17;117(7):2241-6. | |
| Cas No. | 1194961-19-7 | SDF | |
| 别名 | PRT318 | ||
| 化学名 | 2-(((1R,2S)-2-aminocyclohexyl)amino)-4-(m-tolylamino)pyrimidine-5-carboxamide | ||
| Canonical SMILES | O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(C)=C3)N | ||
| 分子式 | C18H27Cl3N6O | 分子量 | 449.81 |
| 溶解度 | DMF: 3 mg/ml,DMF:PBS (pH7.2) (1:30): 0.03 mg/ml,DMSO: Insouble,Ethanol: Insouble,PBS (pH 7.2): Insouble | 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 | 2.2232 mL | 11.1158 mL | 22.2316 mL |
| 5 mM | 0.4446 mL | 2.2232 mL | 4.4463 mL |
| 10 mM | 0.2223 mL | 1.1116 mL | 2.2232 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet