Novel Piperidine-Amide Derivatives as CXCR4 Modulators

­ Application A new class of CXCR4 modulators for metastasis and inflammation. Key Benefits Selective for only one allosteric site on CXCR4. Lower adverse effects. Market Summary Multiple myeloma, acute myeloid leukemia, HIV, and rheumato…

Application
A new class of CXCR4 modulators for metastasis and inflammation.

Key Benefits

  • Selective for only one allosteric site on CXCR4.
  • Lower adverse effects.

Market Summary
Multiple myeloma, acute myeloid leukemia, HIV, and rheumatoid arthritis all involve the G-protein receptor CXCR4. Currently, there is only one FDA-approved CXCR4 antagonist, AMD3100, but the compound has cardiotoxicity issues related to its ability to block Ca2+ flux. Researchers at Emory University have identified ZINC72372983 as having anti-inflammatory effects and upon further development, a 100-fold improvement in binding affinity. This invention could contribute to the immunotherapy drug market which was $130.3 billion in 2019 and is expected to reach $204.4 billion by 2025 with a CAGR of 7.9% 2019-to 2025 (BCC Research PIIM249A).

Technical Summary
Researchers screened for compounds that bind in allosteric sites to find compounds that module the receptor without having adverse effects. Through ligand-based screening, docking ADMET, and PAINS filters the researchers found 7 compounds from a ZINC database that were taken forward in vitro assay. In vitro assay revealed 4 of the 7 compounds had binding constants between 100-10 nm via fluorescence in moderate throughput assay. These 4 were then put through in vitro functional assay revealing that the compound ZINC72372983 had the best inhibitory efficacy against the chemotaxis between CXCR4 and CXCL12.

Developmental Stage
Animal testing was conducted.

Contact Information

TTO Home Page: https://emoryott.technologypublisher.com

Name: Catherine Murari-Kanti

Title: Licensing Associate

Email: cmurari@emory.edu

Phone: (404) 727-0057