The present invention provides an in vivo platform for identifying and determining therapeutic or prophylactic activity of test compounds in delay-type hypersensitivity (DTH) and other inflammatory or cancerous diseases mediated by activation of IKK-βC46A mutants. The in vivo platform of the present invention is a non-human transgenic mammal, e.g., a mouse model, with a site directed mutagenesis at a cysteine residue replaced by alanine in IKK-β protein kinase. The site directed mutagenesis is introduced by a specially designed targeting vector containing a transversion in exon 3 of the Ikbkb genes encoding the IKK-β. The present invention also provides methods for generating the transgenic mammal and for determining and identifying compounds that can inhibit activation of IKK-βC46A mutants.