2. Academic Validation
  3. Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy

Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy

  • ACS Med Chem Lett. 2019 Nov 25;11(1):29-33. doi: 10.1021/acsmedchemlett.9b00382.
Daniel E Jeffries 1,  Corina M Borza 2,  Anna L Blobaum 3 4,  Ambra Pozzi 2 5,  Craig W Lindsley 1 3 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 2 Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 3 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
  • 4 Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
  • 5 Veterans Affairs Medical Center, Nashville, Nashville, Tennessee 37232, United States.
PMID: 31938459 DOI: 10.1021/acsmedchemlett.9b00382
Abstract

Herein, we report the discovery of a potent and selective dual DDR1/2 inhibitor, 7e (VU6015929), displaying low cytotoxicity, good kinome selectivity, and possessing an acceptable in vitro DMPK profile with good rodent in vivo pharmacokinetics. VU6015929 potently blocks collagen-induced DDR1 activation and collagen-IV production, suggesting DDR1 inhibition as an exciting target for antifibrotic therapy.

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