Cyclenium researchers were part of the core R&D team of the pioneering macrocyclic discovery and development company, Tranzyme Pharma.  On the forefront of this rapidly advancing area for over 15 years, the Cyclenium team has developed its proprietary CMRT ("smart," Customized Macrocycles for Recognition of Topologies) Technology that addresses deficiencies in earlier approaches, and designed the QUEST Library of next generation macrocyclic compounds to possess the following key attributes:

  • MW range of 320 to 850 Da
  • Continuous evolution, addition of new compounds and scaffolds each month
  • Directly amenable for use in any HTS system and mode
  • Enables rapid high-throughput solid-phase optimization
  • Displays minimal off-target activity and superior safety profile
  • Provides multiple avenues for accelerating hit-to-lead and lead-to-candidate optimization
  • Includes unique compound designs based upon recurring structural motifs in protein-protein interactions
  • Meets industry standard physicochemical property and handling criteria: solubility, clogP, tPSA, with stability as expected for small molecules
  • Incorporates specific elements designed for blood-brain barrier penetration
  • Easily scalable in solution, reasonable manufacturing costs, applicable to standard formulation approaches
  • Unique structures outside existing patents in macrocycle space
  • Offers exclusive targeted design opportunities for collaboration partners

Cyclenium CMRT Technology Advantages

  • Addresses the high unmet need for PPI-targeting chemistry

  • Provides an alternative to biological drugs (antibodies, proteins, peptides, oligonucleotides)

  • Orally available and blood-brain-barrier (BBB) penetrating macrocycles

  • Compounds behave like traditional small molecules: stability, PK/PD properties, development

  • Well suited to track historically poorly accessible drug targets in broad range of therapeutic areas

    • Protein-protein interactions (oncology, inflammation, metabolic diseases, infectious diseases)

    • Bacteria, viruses, fungi (infectious diseases)

    • Cytokines and chemokines (inflammation, oncology; no small molecule drugs to date)

    • G Protein-Coupled Receptors (CNS, cardio-vascular)

    • Enzymes (proteases, kinases, RNAses, convertases)

In general, macrocyclic molecules offer an underexplored chemical class that provides an attractive alternative to the typical heterocyclic small molecules that dominate current pharmaceutical compound collections.

Macrocyclic Drug Discovery

  • Covers molecular space between traditional small molecules and large bio-molecules
  • Cyclic chemical structures with ring sizes of generally >12 atoms
  • Captures pharmacological properties of larger peptides/proteins in metabolically stable small molecules
  • Offers excellent target fit, high potency and excellent selectivity similar to biologics due to constrained and preorganized conformation
  • Potential to modulate complex drug targets with simple agents
  • Proven on broad range of target classes

For a comparison of Cyclenium and previous generation macrocycle technologies, click here.