TY - JOUR
T1 - Identification of lipid-like salicylic acid-based derivatives as potent and membrane-permeable PTP1B inhibitors
AU - Li, Liang
AU - Tavallaie, Mojdeh S.
AU - Xie, Fangzhou
AU - Xia, Yu
AU - Liang, Yaoyao
AU - Jiang, Faqin
AU - Fu, Lei
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/12
Y1 - 2019/12
N2 - Developing protein tyrosine phosphatase-1B (PTP1B) inhibitors is an important strategy to treat type 2 diabetes mellitus (T2DM). Most existing ionic PTP1B inhibitors aren't of clinical useful due to their low cell-permeability, however. Herein, we introduced a series of lipid-like acid-based (salicylic acid) modules to prepare PTP1B inhibitors, and demonstrated a marked improvement of cell-permeability while maintaining excellent PTP1B inhibitory activity (e.g. compound B12D, IC50 = 0.37 μM against PTP1B and Papp = 1.5 × 10−6 cm/s). We believe that this strategy can be widely utilized to modify potent lead compounds with low cell-permeability.
AB - Developing protein tyrosine phosphatase-1B (PTP1B) inhibitors is an important strategy to treat type 2 diabetes mellitus (T2DM). Most existing ionic PTP1B inhibitors aren't of clinical useful due to their low cell-permeability, however. Herein, we introduced a series of lipid-like acid-based (salicylic acid) modules to prepare PTP1B inhibitors, and demonstrated a marked improvement of cell-permeability while maintaining excellent PTP1B inhibitory activity (e.g. compound B12D, IC50 = 0.37 μM against PTP1B and Papp = 1.5 × 10−6 cm/s). We believe that this strategy can be widely utilized to modify potent lead compounds with low cell-permeability.
KW - Membrane permeability
KW - PTP1B inhibitors
KW - Salicylic acid-based derivatives
KW - T2DM
UR - http://www.scopus.com/inward/record.url?scp=85072836790&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2019.103296
DO - 10.1016/j.bioorg.2019.103296
M3 - Article
C2 - 31585268
AN - SCOPUS:85072836790
SN - 0045-2068
VL - 93
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 103296
ER -