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Autoimmune disease

Rheumatoid arthritis (RA)

Cyclin dependent kinase 4 (CDK4); CDK6

Human genetic studies suggest antagonizing CDK4 or CDK6 activity could be useful for treating RA. A meta-analysis of previously reported genomewide association and mouse knockout studies identified polymorphisms in 98 genes that contributed to RA risk, including 27 genes that encode proteins that are targets of approved RA drugs. Two risk genes-CDK4 and CDK6-encode proteins that are targets of at least three compounds in clinical testing for a range of cancers. Next steps include testing CDK4 and CDK6 inhibitors in models of RA.
Dual CDK4 and CDK6 antagonists in clinical testing for cancer include Pfizer Inc.'s Phase III compound palbociclib (PD-0332991), Novartis AG and Otsuka Pharmaceutical Co. Ltd.'s Phase III compound LEE011 and Eli Lilly and Co.'s Phase II compound LY2835219.

SciBX 7(5); doi:10.1038/scibx.2014.137
Published online Feb. 6, 2014

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Okada, Y. et al. Nature; published online Dec. 25, 2013;
Contact: Robert M. Plenge, Harvard Medical School, Boston, Mass.