Indeno[1,2-b]indole scaffold in drug discovery: An effective template in kinase inhibitor medicinal chemistry

Casein kinase 2 (CK2) is a highly pleiotropic serine/threonine protein kinase whose list of substrates includes >300 proteins implicated in a wide variety of cell functions. The catalytic subunits of CK2 (alpha and/or alpha’) are constitutively active either alone or in combination with the regulatory beta-subunits to give a heterotetrameric protein. High constitutive activity of CK2 is related to contribute to cancer. Based on recent years of effort, a German French collaborative network has developed indeno[1,2-b]indole scaffold for designing novel inhibitors of human CK2.

The aim of this study is to develop functionalized indeno[1,2-b]indoles and to investigate their potential inhibitory activity against human CK2. The different aspects of medicinal chemistry will be discussed, namely synthesis, NMR investigations, X-ray crystallography, CK2 inhibition, in cellulo activities, molecular modelling and physico-chemical properties.