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SpiroChem’s Macrocycle Library delivers clinical candidates
Feb 2024


SpiroChem’s Macrocycle Library delivers clinical candidates

Roche recently reported in two related Nature publications on a new antibiotic compound class, with Zosurabalpin nominated as the first clinical candidate, for treatment of carbapenem-resistant Acinetobacter baumannii (www.nature.com/article1, www.nature.com/article2).

This macrocycle acts through a novel mechanism of action involving inhibition of the LptB2FGC complex, a key component of the bacterial lipopolysaccharide transport system in Gram-negative bacteria.


Cryo EM structure of acinetobacter baylyi LptB2FG bound to lipopolysaccharide and zosurabalpin refined at 3.30 Å resolution (pdb: 8frn). The macrocycle is shown in a stick model (white carbon atoms), lipopolysaccharides in orange sticks, the protein is depicted in cartoon mode.

The initial hits of this compound class originate from a technology that has further been developed into a next generation platform that is now available through SpiroChem.

SpiroChem offers the SpiroQUEST™ Library, a diverse screening library of 8000+ unique macrocycles that:

  • is chemically fully enabled
  • allows access to a virtual space of multi-billion derivatives that can be explored in subsequent hit-to-lead and lead optimization campaigns

Specifically, initial hits from this library can be followed up rapidly:

  • utilizing the technology synthetic platform
  • permitting simultaneous chemical and conformational optimization
  • potentially accelerating the identification of one or more potent and selective lead series against a broad variety of targets, including those often considered intractable or difficult, such as protein-protein interactions (PPI)


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