Advantages:
- The approach of targeting BIN1, a gene associated with AD increases the likelihood of finding effective therapeutic interventions.
- Determining the crystal structure of BIN1's SH3 domain provides detailed structural information which is crucial for designing small molecule inhibitors.
- The research reports promising preliminary results, such as the identification of a compound (#5) with a dissociation constant (KD) similar to the interaction between BIN1's SH3 domain and Tau. This suggests that small molecules can be designed to interact with BIN1 effectively.
Summary:
Our investigators have solved the crystal structure of human BIN1’s SH3 domain. The dissociation constant (KD) for BIN1’s SH3 domain and wildtype tau was identified at 1.136µM, a transient but strong interaction as most SH3 domains bind partners between 1- 100µM. They have conducted a virtual screen to identify small molecule inhibitors against BIN1’s SH3 domain. The screen produced several inhibitor candidates with compound #5 as the lead inhibitor (KD = 15uM).
Structural determination of BIN1’s SH3 domain accomplished by first isolating and purifying the ~12kDa domain by expression in E. coli cells and purification by FPLC.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development