产品说明书
Pacritinib
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同义名 : | SB1518 |
| CAS号 : | 937272-79-2 | |
| 货号 : | A134862 | |
| 分子式 : | C28H32N4O3 | |
| 纯度 : | 97% | |
| 分子量 : | 472.579 | |
| MDL号 : | MFCD22572772 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 4 mg/mL(8.46 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
IP 5% DMSO+water 0.2 mg/mL clear PO 0.5% CMC-Na 50 mg/mL suspension |
| 生物活性 | |||
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| 靶点 |
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| 描述 | The JAK/STAT3 pathway is activated by various cancer types, including glioma, and blockade of the pathway induces cell death in cancer cells. JAKs encompass a family of four (JAK1, JAK2, JAK3 and TYK2) intracellular, non-receptor tyrosine kinases, associated with cytokine receptors. Under normal conditions, activation of the receptor by cytokine binding leads to trans-phosphorylation of JAK and downstream phosphorylation of STAT proteins (pSTAT)[3]. JAK2 phosphorylates cell surface receptors on tyrosine residues creating docking sites for STAT3 proteins. Once STAT3 is recruited to the receptor, it is phosphorylated by JAK2 allowing STAT3 to form a dimer and move into the nucleus where it can activate the transcription of target genes[4]. Pacritinib is a JAK2 and fms-like tyrosine kinase-3 (FLT3) inhibitor with IC50 23 nM and 22 nM. It also suppresses the interleukin-1-directed inflammatory pathway via inhibition of interleukin 1 receptor-associated kinase 1 (IRAK1)[5]. In a phase I study, thirteen AML (acute myeloid leukemia) patients were enrolled, treated with Pacritinib at a dose of 100 mg or 200 mg twice daily following a 3 + 3 dose-escalation in combination with cytarabine and daunorubicin or with decitabine induction. The result demonstrated that pacritinib was well tolerated and had preliminary anti-leukemic activity[6]. In a vivo study, the Stelic animal model (STAM) mouse were given 200 mg/kg Pacritinib orally for twice a day for 10 days. Pacritinib-treated mice had significantly reduced fibrotic areas in liver compared to vehicle control and significantly lower levels of CK18 which demonstrated that pacritinib possess a good antifibrotic effect[7]. Thirty-two mice were xenografted with BT147(brain tumor initiating cells) cells, and treated with pacritinib at a dose of 100 mg/kg. Pacritinib resulted in an increase median survival of 62.5 days which demonstrated pacritinib synergy with TMZ may be another considerable choice therapy for GBM(glioblastoma multiforme)[4]. | ||
| 作用机制 | Pacritinib can bind with the JAK2 enzyme binding pocket. | ||
| 临床研究 | |||||
|---|---|---|---|---|---|
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT02251821 | Primary Myelofibrosis ... 展开 >> Secondary Myelofibrosis 收起 << | Phase 2 | Recruiting | - | United States, Washington ... 展开 >> Fred Hutch/University of Washington Cancer Consortium Recruiting Seattle, Washington, United States, 98109 Contact: Rachel B. Salit 206-667-1317 rsalit@fredhutch.org Principal Investigator: Rachel B. Salit 收起 << |
| NCT02823171 | Healthy | Phase 1 | Completed | - | United States, Indiana ... 展开 >> Covance Clinical Research Unit Inc. Evansville, Indiana, United States, 47710 收起 << |
| NCT02342353 | Non-Small Cell Lung Cancer ... 展开 >> Nonsmall Cell Lung Cancer Carcinoma, Non-Small-Cell Lung 收起 << | Phase 1 | Terminated(Drug shortage) | - | United States, Missouri ... 展开 >> Washington University School of Medicine Saint Louis, Missouri, United States, 63110 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.12mL 0.42mL 0.21mL |
10.58mL 2.12mL 1.06mL |
21.16mL 4.23mL 2.12mL |
| 参考文献 |
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