Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. One of the biggest challenges in drug discovery is to identify high-quality hit and lead compounds. Lead L12 had an IC50 of 8.7 nM and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil, and PK results indicate that L12 could be used as a promising lead for further development. Pharmacokinetic properties of L12 were analyzed by Medicilon.

Reference:

Deyan Wu, et al. Free energy perturbation (FEP)-guided scaffold hopping. Acta Pharm Sin B. 2022 Mar;12(3):1351-1362. doi: 10.1016/j.apsb.2021.09.027.