Dissertation

To affinity and beyond: novel molecular tools to explore solute carrier transport proteins

Despite being the second largest transmembrane protein family after GPCRs, the SLC superfamily has only gained significant attention in early drug development over the past decade.

Author

M.A. Dilweg

Date

02 May 2025

Links

Thesis in Leiden Repository

As a consequence, the search for diverse, high-affinity, and selective inhibitors as well as functionalized small molecule probes remains crucial. Hence, advancing fundamental drug discovery research for SLCs to affinity and beyond is essential for systematically developing tool molecules that enhance our understanding and support drug design for this important yet relatively underexplored drug target. This thesis explores the design and synthesis of small molecules and functionalized small molecule probes – namely covalent inhibitors, targeting ENT1, NET, and DAT. These inhibitors have been characterized using molecular pharmacology and structure-based computational methods to offer new insights into these therapeutically significant SLCs.

• covalent inhibitors
• dopamine transporter
• medicinal chemistry
• molecular probes
• norepinephrine transporter
• solute carrier transporters