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

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.

SUBMITTER: Jeffries DE

PROVIDER: S-EPMC6956352 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Jeffries Daniel E DE Borza Corina M CM Blobaum Anna L AL Pozzi Ambra A Lindsley Craig W CW

ACS medicinal chemistry letters 20191125 1

Herein, we report the discovery of a potent and selective dual DDR1/2 inhibitor, <b>7e</b> (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. ...[more]

PMID: 31938459

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