856827-99-1Relevant articles and documents
Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators
Kolari?, Anja,?vajger, Urban,Toma?i?, Tihomir,Brox, Regine,Frank, Theresa,Minovski, Nikola,Tschammer, Nuska,Anderluh, Marko
, p. 68 - 90 (2018)
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation. Para-methoxy substitution leads to functional antagonism, while para-chloro triggers agonism. Additionally, we discovered that chemotaxis is not completely correlated with G protein pathways. This is the first work in which we have on a series of compounds successfully demonstrated that it is possible to produce selective as well as dual-acting modulators of chemokine receptors, which is very promising for future research in the field of discovery of selective or dual modulators of chemokine receptors.
