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F-box protein 3 (FBXO3)

Patient sample and mouse studies suggest FBXO3 inhibitors could be used to treat inflammation caused by infectious diseases. In 8 of 60 human peripheral blood mononuclear cell (PBMC) samples, a loss-of-function FBXO3 mutation was identified, which led to lower cytokine production in response to lipopolysaccharide (LPS) than wild-type FBXO3. In a mouse model for pneumonia, small hairpin RNA-mediated knockdown of FBXO3 decreased markers of inflammation and increased survival compared with no knockdown. In the model, the FBXO3-targeting benzathine derivative BC-1215 decreased markers of inflammation compared with vehicle. Next steps include evaluating the pharmacokinetics and toxicity of BC-1215 and related molecules.

SciBX 6(14); doi:10.1038/scibx.2013.339
Published online April 11, 2013

Patent application filed; available for licensing

Chen, B.B. et al. Nat. Immunol.; published online March 31, 2013;
Contact: Rama K. Mallampalli, University of Pittsburgh, Pittsburgh, Pa.