SGC-CK2-1 Is an Efficient Inducer of Insulin Production and Secretion in Pancreatic β-Cells.

Mandy Pack,Mathias Montenarh,Claudia Götz,Selina Wrublewsky

doi:10.3390/pharmaceutics14010019

Abstract

The pyrazolopyrimidine based compound SGC-CK2-1 is a potent and highly specific CK2 inhibitor and a new tool to study the biological functions of protein kinase CK2 irrespective from off-target effects. We used this compound in comparison with the well-established CK2 inhibitor CX-4945 to analyze the importance of CK2 for insulin production and secretion from pancreatic β-cells. Both inhibitors affected the proliferation and viability of MIN6 cells only marginally and downregulated the endogenous CK2 activity to a similar level. Furthermore, both inhibitors increased the message for insulin and boosted the secretion of insulin from storage vesicles. Thus, regarding the high specificity of SGC-CK2-1, we can clearly attribute the observed effects to biological functions of protein kinase CK2.

Highlights

The human kinome encompasses more than 500 kinases [1]
We asked whether the published effects on functions of pancreatic β-cells after inhibition with different CK2 inhibitors are true for the treatment with SGC-CK2-1
By using larger panels of different kinases as well as the use of the inhibitors in different biological systems, it turned out that at least the class of ATP competitive CK2 inhibitors have off target effects [29,33,35,47,48]

Summary

Introduction

The human kinome encompasses more than 500 kinases [1] One of these kinases, namely CK2 (formerly known as casein kinase 2) phosphorylates a great number of proteins which are implicated in central biological processes leading to the difference between life and death of a cell, cell proliferation, DNA damage response, differentiation of cells, controlling of angiogenesis, and ion channel activation [2,3,4,5,6,7]. It was shown that CK2 is a potent suppressor of apoptosis, which is a hallmark of cancer [11] Due to this particular property of CK2, there are many attempts to inhibit the kinase activity in order to stop cell proliferation and tumor growth [10,12,13]. There is a still growing list of CK2 inhibitors, most of which are ATP competitive inhibitors [14]

Methods

Results

Conclusion