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GDC-0879, a BRAF

GDC-0879, a BRAF

Jonas Sieber, Nicolas Wieder, Abbe Clark, Manuel Reitberger, Sofia Matan, Jeannine Schoenfelder, Jianming Zhang, Anna Mandinova, Joshua Adam Bittker, Juan Gutierrez, Ozan Aygün, Namrata Udeshi, Steven Carr, etc.

Cell Chem Biol. 2018 Feb 15;25(2):175-184.e4.

PMID: 29249695

Abstract:

Progressive kidney diseases affect approximately 500 million people worldwide. Podocytes are terminally differentiated cells of the kidney filter, the loss of which leads to disease progression and kidney failure. To date, there are no therapies to promote podocyte survival. Drug repurposing may therefore help accelerate the development of cures in an area of tremendous unmet need. In a newly developed high-throughput screening assay of podocyte viability, we identified the BRAFV600E inhibitor GDC-0879 and the adenylate cyclase agonist forskolin as podocyte-survival-promoting compounds. GDC-0879 protects podocytes from injury through paradoxical activation of the MEK/ERK pathway. Forskolin promotes podocyte survival by attenuating protein biosynthesis. Importantly, GDC-0879 and forskolin are shown to promote podocyte survival against an array of cellular stressors. This work reveals new therapeutic targets for much needed podocyte-protective therapies and provides insights into the use of GDC-0879-like molecules for the treatment of progressive kidney diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP905281767	GDC-0879		905281-76-7	Price

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