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IWP L6

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Chemical Structure| 1427782-89-5 同义名 : PorcnInhibitorIII;Wnt Pathway Inhibitor XIX
CAS号 : 1427782-89-5
货号 : A735189
分子式 : C25H20N4O2S2
纯度 : 98%
分子量 : 472.582
MDL号 : MFCD27937771
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(42.32 mM)，配合低频超声，并水浴加热至45℃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
动物实验配方：
生物活性
描述 Porcupine (Porcn) is a membrane bound O-acyltransferase (MBOAT) family protein, which catalyzes the palmitoylation of Wnt to enable its exit from the secretory pathway and subsequent activation of cellular responses. IWP L6 is a subnanomolar Porcn inhibitor with IC50 value of 0.5 nM. In vitro, treatment of the HEK293 cells with 2.5 μM IWP L6 effectively suppressed the phosphorylation of the cytoplasmic Wnt pathway effector disheveled 2 (Dvl2)[2]. Treatment of T.cruzi trypomastigotes infection of Bone marrow-derived macrophages (BMM) with 20 μM IWP L6 inhibited both p-CaMKII upregulation and NFATc1 activation. IWP L6 at concentration of 20μM resulted in a inhibitory effect on intracellular parasite growth by inhibiting the secretion of Wnt proteins in T.cruzi trypomastigotes infection of BMM[3]. In vivo stability analysis of IWP L6 showed that IWP L6 was stable in human plasma over 24h, it was rapidly metabolized in rat plasma, murine plasma and the murine liver S9 fractions with t1/2 of 190 min, 2 min and 26 min, respectively. IWP L6 effectively inhibited posterior axis formation of juvenile zebrafish, a Wnt/β-catenin dependent developmental process, at concentration range of 1 – 5 μM[2]. Intraperitoneal administration of IWP L6 at 7.5 mg/kg could maintain inhibited both Wnt/β-catenin as well as Wnt/Ca2+ signaling pathways until 18 days post-infection in B6 mice infected with 5,000 T. cruzi trypomastigotes. In addition, treatment with IWP-L6 significantly reduced parasite load in liver and heart of B6 mice infected with 5,000 T. cruzi trypomastigotes during the chronic phase of the disease[3].
实验方案
1mg 5mg 10mg

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

[1]Wang X, et al. J Med Chem. 2013, 56(6), 2700-2704.

[2]Wang X, Moon J, Dodge M E, et al. The Development of Highly Potent Inhibitors for Porcupine. Journal of Medicinal Chemistry, 2013, 56(6): 2700-2704.

[3]Volpini X, Ambrosio L F, Fozzatti L, et al. Trypanosoma cruzi Exploits Wnt Signaling Pathway to Promote Its Intracellular Replication in Macrophages. Frontiers in Immunology, 2018