Inhibiting CDK7 for rheumatoid arthritis

Inhibiting the cyclin-dependent protein kinase CDK7 could help treat rheumatoid arthritis by preventing pausing of the RNA polymerase Pol II, a rate-limiting step in the transcription of >70% of inducible genes in macrophages, which decreases pro-inflammatory gene expression in pathogenic macrophages while sustaining expression of anti-inflammatory genes, thus decreasing the joint destruction caused by chronic inflammation.

In primary synovial tissue cultures from rheumatoid arthritis patients, a CDK7 inhibitor tool compound decreased expression of genes involved in pro-inflammatory response and pathogenic macrophage infiltration, and increased expression of markers associated with anti-inflammatory macrophages, compared with vehicle. ...