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Cerdulatinib(PRT062070)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Cerdulatinib(PRT062070)图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
10mg电议
50mg电议
100mg电议

产品介绍
Cerdulatinib (PRT062070) (PRT062070) 是一种选择性 Tyk2 抑制剂,IC50 为 0.5 nM。 Cerdulatinib (PRT062070) (PRT062070) 也是一种双重 JAK 和 SYK 抑制剂,对 JAK1、2、3 和 SYK 的 IC50 分别为 12、6、8 和 32。

Cell lines

DLBCL (diffuse large B-cell lymphoma) cells: germinal center B-cell (GCB) subtype, activated B-cell (ABC) subtype.

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

6 h

Applications

Cerdulatinib induces apoptosis in both GCB and ABC cell lines by caspase 3 and PARP cleavage. Cerdulatinib also triggers apoptosis and cell cycle arrest in BCR-stimulated DLBCL cells. Cerdulatinib blocks JAK/STAT and BCR signaling in both ABC and GCB cell lines as well.

Animal models

Female Lewis rats collagen-induced arthritis (CIA) model

Dosage form

Oral gavage twice daily.

Applications

3 mg/kg of Cerdulatinib suppresses the inflammation and reverses relative to pretreatment levels at 5 mg/kg. Cerdulatinib also dose-dependently leads to significant improvements in inflammatory infiltrate within the synovium and the integrity of the articular cartilage. Moreover, Cerdulatinib treatment affects anticollagen antibody formation and reduces 50% of circulating antibody titers at the 1.5, 3, and 5 mg/kg doses.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

产品描述

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.