Formylchromone derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors.
Formylchromone inhibits a human protein tyrosine phosphatase PTP1B with a IC(50) value of 73 microM. The chemical reactivity of formylchromone was adjusted by substitution at various positions of the formylchromone skeleton. In an initial assessment of the structure-activity relationship, the most potent inhibitor showed an IC(50) of 4.3 microM against PTP1B and strong or medium selectivity against other human PTPases, LAR and TC-PTP. This compound, however, was not selective against microbial PTPases, YPTP1 and YOP. The potency and selectivity of the formylchromone derivatives expecting further improvements provides a novel pharmacophore for the design of drugs for the treatment of type 2 diabetes and obesity.
Shim
Yi Sup
YS
Department of Chemistry and Institute of Molecular Cell Biology, Inha University, 253 Yonghyun-dong, Nam-ku, Incheon 402-751, South Korea.
Kim
Ki Chul
KC
Chi
Dae Yoon
DY
Lee
Keun-Hyeung
KH
Cho
Hyeongjin
H
D001419:Bacteria / Q000201:enzymology; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002867:Chromones; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases