BH3 mimetics derived from Bim-BH3 domain core region show PTP1B inhibitory activity.


School of Medicine and Pharmacy, Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao 266003, China; Marine Biomedical Research Institute, Qingdao 266071, China. Electronic address: [Email]


A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD = 8.38 nmol/L), inhibitory activity (IC50 = 1.20 μmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model. These results may indicate a new direction for the application of BH3 peptide mimetics and promising PTP1B peptide inhibitors could be designed and developed based on SM-6.


BH3 peptide mimetics,Insulin resistance,PTP1B inhibitors,Protein tyrosine phosphatase 1B,Type 2 diabetes mellitus,