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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-alpha expression in T cells
Jan Rether1, Gerhard Erkel, Timm Anke
1Institut für Biotechnologie und Wirkstoff-Forschung e. V., Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern, Germany.
Abstract:
Novel hexahydroimidazo[1,2-a]pyridines prepared by the addition of ethyl (1-benzylimidazolidin-2-ylidene)acetate (2) to the fungal metabolite podoscyphic acid (1a) and esters of 1a have been evaluated for their ability to inhibit the inducible TNF-alpha promoter activity in T cells. The methyl ester 3b is the most potent, inhibiting the TNF-alpha driven reporter gene expression in Jurkat T cells with an IC(50)-value of 2.0 microg/ml (3.6 microM). In addition, compound 3b inhibited the inducible TNF-alpha production in the myelomonocytic U937 cells with an IC(50)-value of 4.6 microM.
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