Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections
Abstract
Emerging viruses, such as dengue (DENV) and Ebola (EBOV), pose threats to military and global health. There are no approved drugs or vaccines available against these viruses. Our overall goal is to develop broad-spectrum antiviral drugs with a high genetic barrier to resistance by targeting host proteins that are critical to the life cycle of multiple viruses. The goals of this project are to optimize novel, selective lead inhibitors of AAK1 and GAK, host kinases we discovered as targets for broad-spectrum antivirals, and advance their development to a pre-IND stage. This approach would also protect against biothreat agents from multiple other viral families. During the past year we have optimized our inhibitors and have generated one GAK inhibitor with improved antiviral activity against DENV and EBOV, which is combined with improved metabolic stability and good kinase activity and selectivity. Moreover, we have identified a novel scaffold of AAK1 inhibitors and have designed a novel dual AAK1 and GAK inhibitor with good kinase activity and selectivity and potent antiviral activity. We are now advancing some of these compounds into mouse studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1050826
Entities
People
- Jennifer M. Brannan
- Shirit Einav
- Steven De Jonghe
- Szuyuan Pu
Organizations
- Stanford University School of Medicine