Human loss of function variants in 17βHSD13 reduce risk and progression of metabolic and alcohol related liver disease, positioning this liver enzyme as a promising therapeutic target. Yet incomplete mechanistic understanding of the protective effects has limited reliable biomarker identification for small molecule inhibitor engagement. In this webinar, Thomas Lundbäck will present a quantitative approach to assess target engagement of BI-3231, a reference inhibitor, using liver homogenates from humanized 17βHSD13 mice alongside complementary biophysical and cellular assays. By integrating orthogonal readouts with functional live cell data, he shows how target occupancy can be established in biologically relevant settings and why liver metabolic status should be incorporated into experimental design and interpretation.
Webinar Topics
- Challenges of developing drugs against genetically validated targets when biomarkers are uncertain.
- Why controlled variation of experimental conditions is essential before drawing conclusions on target engagement in relevant biological samples.
- The importance of mechanistic insight and, when applicable, incorporating metabolic state into study design and data interpretation.
Featuring Insights from
Thomas Lundbäck
,
PhD
Thomas Lundbäck is Senior Director at the AstraZeneca R&D organisation in Gothenburg, where he leads a department within Discovery Sciences focused on in vitro profiling of small molecules, PROTACs, antisense oligonucleotides, and siRNAs. The department supports research in cardiovascular, renal, metabolic, respiratory, and inflammatory diseases, and besides SAR-profiling assays provides also early assessment of drug metabolism and pharmacokinetics (DMPK) globally within AstraZeneca.
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