Formylchromone derivatives as irreversible and selective inhibitors of human protein tyrosine phosphatase 1B. Kinetic and modeling studies.
A series of formylchromone derivatives were synthesized as PTP1B inhibitors and some of them were potent against PTP1B with IC50 values as low as 1.0 microM. They exhibited remarkable selectivity for PTP1B over other human PTPases. Kinetic studies revealed that formylchromone derivatives are irreversible and active site-directed inhibitors. Molecular modeling study identified the orientation of the inhibitor bound at the active site of PTP1B.
Shim
Yi Sup
YS
Department of Chemistry and Institute of Molecular Cell Biology, Inha University, Yonghyun-dong, Nam-ku, Incheon 402-751, Republic of Korea.
Kim
Ki Chul
KC
Lee
Kyung A
KA
Shrestha
Suja
S
Lee
Keun-Hyeung
KH
Kim
Chan Kyung
CK
Cho
Hyeongjin
H
D002867:Chromones / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002867:Chromones; D004791:Enzyme Inhibitors; C502480:formylchromone; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases