Amazing research on the drug discovery of a series of macrolides called sequanamycins (bacterial ribosome inhibitors) with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). The mechanism of action is similar to that of erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with potential use in new regimens against drug-susceptible and drug-resistant TB.
Sanofi, Texas A&M University, Evotec – Jidong ZHANG, Kwame Amaning, Zhicheng (Z.Chen) Cui, Scott Franzblau, Florence Bordon-Pallier, Cathy Cantalloube, Stefaan Sansen, Laurent Fraisse, Alexey Rak, Lasse Jenner, Gulnara YUSUPOVA, Junjie Zhang, Takushi Kaneko, Nader Fotouhi, Sandeep Tyagi, Fabrice B., Anna Upton, James Sacchettini and Sophie LAGRANGE, PhD
