Discovery of Small-Molecule Inhibitors of the TLR1/TLR2 Complex†
Dr. Kui Cheng
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorDr. Xiaohui Wang
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorShuting Zhang
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Hang Yin
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)Search for more papers by this authorDr. Kui Cheng
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorDr. Xiaohui Wang
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorShuting Zhang
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Hang Yin
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)
Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309 (USA)Search for more papers by this authorWe thank the U.S. National Institutes of Health (DA026950, DA025740s and NS067425) for financial support of this work. The sTLR2 DNA plasmid was kindly provided by Dr. Chiaki Nishitani and Dr. Yoshio Kuroki.
Graphical Abstract
An important regulator of innate immunity, the protein complex of Toll-like receptors 1 and 2 (TLR1/TLR2) provides an attractive target for the treatment of various immune disorders. The novel compound CU-CPT22 can compete with the binding of the specific lipoprotein ligand to TLR1/TLR2 (see picture) with high inhibitory activity and specificity. Repression of downstream signaling from TNF-α and IL-1β was also observed.
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