US EPA

7307380 

Journal Article 

Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor 

He, Y; Dou, H; Gao, D; Wang, T; Zhang, M; Wang, H; Li, Y 

2019 

Yes 

Bioorganic & Medicinal Chemistry
ISSN: 0968-0896
EISSN: 1464-3391 

27 

19 

115015 

English 

31420256 

10.1016/j.bmc.2019.07.031 

WOS:000484396400002 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070505312&doi=10.1016%2fj.bmc.2019.07.031&partnerID=40&md5=76532a16ed226d06e360b874d6d7e9a4
Exit
 

Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNFα and MCP-1 and apparently inhibited IKK/NF-κB pathway. 

Anti-inflammatory effects; Dual FABP4/5 inhibitor; Lipolysis inhibition; Structure-based design