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PRT-060318
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。
PRT-060318图片
CAS NO:1194961-19-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)340.42
FormulaC18H24N6O
CAS No.1194961-19-7 (free base)
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 75 mg/mL (166.7 mM)
Water: <1 mg/mL
Ethanol: 75 mg/mL (166.7 mM)
SMILESO=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(C)=C3)N
SynonymsPRT318; PRT060318; PRT 060318; PRT-060318; PRT-318; PRT 318; P14-276.
实验参考方法
In Vitro

In vitro activity: PRT318 inhibits platelet activation via GPVI/FcRγ, an ITAM receptor complex, but not via ADP or thrombin, which are G-protein coupled receptors. PRT318 effectively antagonizes CLL(chronic lymphocytic leukemia) cell survival after BCR triggering and in nurse-like cell-co-cultures. PRT318 inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering.


Kinase Assay: PRT-060318 (also known as PRT318) is a novel, potent, selective inhibitor of the Syk tyrosine kinase, as an approach to HIT treatment. 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.


Cell Assay: 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. The numbers of cells treated with various doses of PRT318 are followed over time. PRT318 inhibits growth of the sensitive cell lines in a dose-dependent manner. Two sensitive (LY7 and LY18) and 2 resistant (LY3 and LY4) cell lines are treated with indicated doses of PRT318.

In VivoIn both rabbit and pig models, intravenous infusion of PRT060318 targets maximal inhibition of Syk kinase activity and significantly inhibits arterial thrombosis. The antithrombotic activity of PRT060318 in pigs is remarkable because it was achieved with complete inhibition of CVXN-induced platelet aggregation, with no effect on ADP-induced platelet aggregation, and no prolongation of ear bleeding time. Also, Syk inhibitor PRT318 is an active agent in HIT. Inhibition of Syk signaling with the orally bio-available PRT318 limits the thrombocytopenic and thrombotic effects of HIT IC 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.
Animal modelMice, rabbit, pig models
Formulation & Dosage30 mg/kg; i.p.
ReferencesBlood. 2011 Feb 17; 117(7): 2241-46; Leukemia. 2012 Jul;26(7):1576-83; Blood. 2011 Nov 3;118(18):5000-10.