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Synthesis of spatially diverse, small molecules for fragment-based drug discovery screening libraries

Technology #2020-042

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1,4 thiazapanone and 1,4 thiazapane
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Researchers
Will Pomerantz, PhD
Associate Professor, Dept. of Chemistry
External Link (chem.umn.edu)
Managed By
Kenneth Karanja
Technology Licensing Officer 612-624-4531
Patent Protection

Provisional Patent Application Filed
A method to synthesize small compounds with higher three-dimensionality, creating more diverse small fragment libraries for screening.

Shaping up compound-fragment libraries

The screening of small molecule fragments as opposed to large, highly-functionalized compounds used for high throughput screening has been a successful tool in identifying ligands to target a diverse range of protein classes. One major limitation with fragment-based ligand discovery (FBLD) is that many traditional fragment libraries are comprised mostly of flat, aromatic-rich compounds (“2D”). Addition of fragments with more three dimensional character (“3D”), can augment library diversity capturing unique chemical space that relative to conventional FBLD libraries. In addition, protein specificity and physicochemical properties of fragments can be improved. In an effort to fill this gap, researchers in Dr. Pomerantz’s lab at the University of Minnesota have designed a method to synthesize low molecular weight 1,4-thiazepan-5-one and 1,4-thiazepane fragments with a high degree of 3D structure. Testament to their value, 1,4-thiazepanes, were shown to specifically inhibit the anti-cancer BET bromodomain protein targets. This inhibition was achieved by specific binding of the compound to the BET bromodomain of BRD4 (preferential to other bromodomain-containing proteins).

Phase of Development

Successful synthesis of multiple substituted 1,4-thiazepan-5-ones.

Key Benefits & Differentiators

  • Increased chance of identifying unique compounds: Creation of under-represented compounds with high three-dimensionality brings diversity to fragment libraries.
  • Higher binding specificity: Synthesis of spatially-diverse 3D compounds which have been shown to have higher selectivity than flat, 2D molecules.
  • Biologically active compounds: 1,4-thiazepanes have been shown to bind the cancer target BRD4 and have potential as drugs or chemical probes to study and treat various diseases.

Applications

  • Compound library creation
  • Chemical synthesis
  • Drug development


Ready for Licensing

This technology is now available for license! The University is excited to partner with industry to see this innovation reach its potential. Please contact Kenneth Karanja to share your business’ needs and your licensing interests in this technology. The license is for the sale, manufacture or use of products claimed by the patents.