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Cerdulatinib (PRT062070)

现货
Catalog No.
B8023
Syk/JAK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
10mg
¥ 1,050.00
现货
50mg
¥ 3,200.00
现货
100mg
¥ 4,700.00
现货

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Background

Cerdulatinib (PRT062070) is a potent and selective inhibitor of Syk and JAK.[1]

The JAK/STAT cascade, which has been implicated in hematopoiesis and cytokine signaling, is present in humans and flies. Worms. The SYK/ZAP70 kinases play an important role in human T and B cell signaling.[3]

Cerdulatinib can induce apoptosis via down-regulation of MCL1 protein and PARP cleavage. Through the inhibition of RB phosphorylation and down-regulation of cyclin E,the Cerdulatinib can also block G1/S transition and cause cell cycle arrest. Further analyses of the cell signaling activities showed that STAT3 phosphorylation was sensitive to inhibition by cerdulatinib in ABC cell lines while phosphorylation of SYK, PLCg2, AKT and ERK is reported to be sensitive to inhibition by cerdulatinib in GCB cell lines.[2]

Cerdulatinib is effective in rodent models of B-cell lymphoma and autoimmune disease and has exhibited anti-tumor activity in genetically diverse B-cell lymphoma cell lines and is more effective than Syk- or Jak- selective inhibitors alone.[1]

References:
[1] Manish Patel , Pau Hamlin, MD, etal. , A Phase I Open-Label, Multi-Dose Escalation Study of the Dual Syk/Jak Inhibitor PRT062070 (Cerdulatinib) in Patients with Relapsed/Refractory B Cell Malignancies. Blood: 124 (21) ; December 6, 2014.
[2] Y.  Lynn Wang, MD PhD, Jiao Ma, PhD, etal., SYK and STAT3 Are Active in Diffuse Large B-Cell Lymphoma: Activity of Cerdulatinib, a Dual SYK/JAK Inhibitor. Blood: 124 (21) ; December 6, 2014.
[3]Morrison DK, Murakami MS, Cleghon V.   Protein kinases and phosphatases in the Drosophila genome. J Cell Biol. 2000 Jul 24;150(2):F57-62.

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt445.54
Cas No.1198300-79-6
FormulaC20H27N7O3S
Solubility≥22.3mg/mL in DMSO
Chemical Name4-(cyclopropylamino)-2-((4-(4-(ethylsulfonyl)piperazin-1-yl)phenyl)amino)pyrimidine-5-carboxamide
SDFDownload SDF
Canonical SMILESNC(C1=CN=C(NC2=CC=C(N3CCN(S(=O)(CC)=O)CC3)C=C2)N=C1NC4CC4)=O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

DLBCL弥漫性大B细胞淋巴瘤细胞:生发中心B细胞(GCB)亚型,活化的B细胞(ABC)亚型。

制备方法

溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

6 h

实验结果

在GCB和ABC细胞系中,Cerdulatinib通过切割caspase 3和PARP诱导细胞凋亡。在BCR刺激的DLBCL细胞中,Cerdulatinib引发凋亡和细胞周期停滞。在ABC和GCB细胞系中,Cerdulatinib阻断JAK/STAT和BCR信号传导。

动物实验 [2]:

动物模型

胶原诱导关节炎(CIA)的雌性Lewis大鼠模型

给药剂量

每天两次口服

实验结果

相对于5 mg/kg的预处理水平,3 mg/kg的cerdulatinib抑制炎症和逆转。Cerdulatinib以剂量依赖性的方式显著改善滑膜内炎症浸润和关节软骨完整性。此外,1.5、3和5 mg/kg剂量的cerdulatinib影响抗胶原抗体形成,并将循环抗体滴度降低50%。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Ma J, Xing W, Coffey G et al. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015 Nov 5.

2. Coffey G, Betz A, DeGuzman F et al.The novel kinase inhibitor PRT062070 (Cerdulatinib)demonstrates efficacy in models of autoimmunity and B-cell cancer. J Pharmacol Exp Ther. 2014 Dec;351(3):538-48.

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