Discovery of small molecular inhibitors for severe asthma and COPD.
|Coordinator||Lunds universitet - Institutionen för experimentell medicinsk vetenskap, Lund|
|Funding from Vinnova||SEK 5 000 000|
|Project duration||November 2010 - October 2014|
Purpose and goal
The goal was to discover small molecular drug opportunity directed at viral-induced severe asthma and COPD. These disease phenotypes represent major unmet medical need and account for more than 50% of health care costs for asthma and COPD. Our project has demonstrated that several chemical classes have target efficacy and exhibit increasing selectivity. Yet, clear limitations are revealed. The novel knowledge generated by the project underpins a new, much refined goal regarding desired target selectivity.
Results and expected effects
We discover inhibition of a pathogenic protein (TSLP) by five chemical classes of compounds. Yet, potency is insufficient. Our discoveries of relatively selective anti-TSLP effects have led us to novel observations at transcriptional level, which unexpectedly have connected production of TSLP and antiviral interferons. Our research underpins novel hypotheses regarding interferon production. We now discover molecular opportunity of combining inhibition of TSLP with stimulation of interferons.
Approach and implementation
This project had access to novel chemical libraries relevant to drug opportunity discovered by the project leader. Pharmacologists and chemists collaborated on structure-activity studies. Our approach involved basic research with unexpected discoveries significantly guiding our drug project regarding effect profiles and molecular mechanisms. Thus, we made realistic milestone adjustments. Our project has evidently developed the experimental research front and TSLP remains a highly topical target.