Macrocycle Screening Library Compounds


Macrocyclic compounds for protein-protein interaction inhibition and other targets

Introduction

The use of synthetic macrocycles is becoming a well-recognized and successful approach for low druggability targets such as antimicrobial, antiviral and protein-protein interaction. Topologically, macrocycles have the unique ability to span large surface areas while remaining conformationally restricted compared to acyclic molecules of equivalent molecular weight. Macrocyclization reduces overall polarity and enhances membrane penetration. Taken together these attributes make macrocycles a powerful approach for any lead discovery program against challenging targets. Macrocycles are typically defined as a carbo- or, more likely, a heterocycle comprising 12 or more heavy atoms and are often perceived as difficult to synthesize and challenging to incorporate chemical diversity. Through focusing on solutions to the synthetic challenges the chemists at ChemBridge have produced a diverse library of over 11,000 macrocycles that are in stock and available for purchase.

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to view the Macrocycle Library product sheet.


Characteristics

ChemBridge has developed a diverse, easily modifiable collection of synthetic macrocycles intended to be accessible to both industry and academic researchers for use in hit generation. ChemBridge chemists have developed synthetic strategies for the synthesis and functionalization of macrocyclic compounds based on novel synthetic macrocyclic scaffolds. A first set of approximately 7,000 macrocycles was launched initially, and ChemBridge has now followed with the release of an additional 4,000 novel synthetic macrocycles incorporating proprietary fragments into the macrocycle rings. Currently, the Macrocycle Library represents more than 11,000 synthetic macrocycles. Researchers have the option to custom select from the library or acquire the full library.

General characteristics of compounds in the ChemBridge Macrocycle Library include:

  • Molecular weight range up to 800
  • Primary ring size ranging from 11 to 27 atoms
  • Heterocyclic primary rings
  • Scaffolds with and without peptidic backbone elements as part of the macrocyclic ring
  • Scaffolds with and without fused rings as part of the primary macrocyclic ring


Macrocycle CNS Subset

An analysis of the initial 6,000 synthetic macrocycles produced by ChemBridge was performed to identify macrocycles that may be suitable for CNS research. A CNS MPO score approach was coupled with a detailed 3D conformational analysis (performed to examine the potential for formation of intramolecular hydrogen bonds). Data from the conformational analysis was used to adjust the HBD and TPSA values and resulting MPO score for each macrocycle to identify a subset with an “adjusted MPO” score ≥ 4.0. Click here for more information.


Format

  • Download structures and custom select Macrocycle Library compounds
  • Compounds can be provided in 96-well and 384-well format
  • Compounds are available as DMSO solutions or dry films
  • Minimum purchase amount of 1 micromole for counts less than 2,000; minimum purchase amount of 0.25 micromole for counts of 2,000 or higher


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