The team led by Professor Luo Haibin from the School of Pharmacy of Hainan University has published a research paper entitled "Free Energy Perturbation (FEP)-Guided Scaffold Hopping" in Acta Pharmaceutica Sinica B, a medical journal of the Chinese Academy of Sciences.

HNU was the first completion unit on the paper, while Luo and researcher Huang Yiyou from HNU's School of Pharmacy were the co-corresponding authors. Professor Wu Deyan from HNU's School of Pharmacy and Associate Professor Zheng Xuehua from Guangzhou Medical University were the co-first authors of the paper.

Luo's team used the self-developed new method of FEP medicine design to develop a new technology of "scaffold hopping". This method can significantly improve the prediction of the binding ability of the target to the new scaffold framework and obtain a new framework with high activity, thereby improving the discovery and optimization efficiency of lead structures, as well as promoting the transformation of innovative medicine development from lead structures to candidate medicines.

Taking the discovery of phosphodiesterase type 5 (PDE5) inhibitor as an example, a new scaffold compound L12 with comparable activity was precisely obtained from the scaffold hopping of the medicine Cialis. 

Through subtype selectivity studies, protein-small molecule co-crystal studies, and preliminary medicine forming studies, it was discovered that compound L12 had high efficiency and low toxicity candidates, while also having the potential to be developed as a new anti-pulmonary hypertension medicine candidate. It further verifies the effectiveness and feasibility of the new scaffold hopping technology based on FEP.

Advanced computational scaffold hopping method.