Translocase 1 (TL1) enzyme is a very attractive target for development of new drugs:
• essential for biosynthesis of the peptidoglycan layer of the bacterial cell wall
• inhibition leads to cell death
• unique to bacteria, absent in eukaryotic cells
• no antibiotics on the market targeting TL1.
The semi-synthetic nucleoside-based Capuramycins inhibit TL1 enzyme. Sequella licensed the Capuramycin class from Daiichi-Sankyo in 2004. SQ641, the lead drug candidate in the class with potent activity against Mycobacterium tuberculosis (Mtb) and non-tuberculous Mycobacteria, undergoes preclinical development at Sequella. Sequella has also initiated a program to develop new TL1 inhibitors with enhanced pharmacological properties and in vivo activity against Mtb. In addition, we are exploring the core structure of Capuramycins to discover modifications that might enable broader spectrum activity.
