An Innovation 10 Years in the Making: The Stories in the Pages of .

Innovation in medicinal chemistry has been at the heart of since the journal's founding 10 years ago. In his inaugural editorial, Editor-in-Chief Dennis Liotta laid out a vision for the journal to become the "premier international journal for rapid communication of cutting-edge studies," and, after 10 years, it has become exactly that. The great hope of drug discovery scientists is that their innovations will lead to new therapeutics to treat unmet medical needs.

Inhaled Janus Kinase (JAK) inhibitors for the treatment of asthma.

Multiple asthma-relevant cytokines including IL-4, IL-5, IL-13, and TSLP depend upon JAKs for signaling. JAK inhibition may, therefore, offer a novel intervention strategy for patients with disease refractory to current standards of care. Multiple systemically delivered JAK inhibitors have been approved for human use or are under clinical evaluation in autoimmune diseases such as rheumatoid arthritis.

Development of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors.

A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocrystal structures with the protein and small-molecule crystal structures, yielded a series of dihydrobenzofurans.

Kinase Inhibitors for the Treatment of Immunological Disorders: Recent Advances.

Small molecule inhibitors targeting autoimmune and inflammatory processes have been an area of intense focus within academia and industry. Much of this work has been aimed at key kinases operating as central nodes in inflammatory signaling pathways. While this focus has led to over 30 FDA-approved small molecule kinase inhibitors, only one is currently approved for autoimmune and inflammatory diseases.