Pachter J A
Schering-Plough Research, Bloomfield, New Jersey 07003.
Mol Pharmacol. 1991 Jul;40(1):107-11.
K-76COONa, a fungal product that was previously isolated for its inhibition of complement activation, was found to inhibit myo-inositol monophosphatase activity. K-76COONa was slightly more potent than lithium, with a Ki of approximately 0.5 mM. Kinetic analyses with D-myo-inositol 1-phosphate as the substrate showed that myo-inositol monophosphatase inhibition by K-76COONa was noncompetitive relative to substrate but competitive with activation by magnesium. Higher concentrations of K-76COONa were necessary to inhibit myo-[3H]inositol 1,4-bisphosphate hydrolysis by inositol 1,4-bisphosphate/inositol 1,3,4-trisphosphate 1-phosphatase (IC50 = approximately 7.5 mM). K-76COONa may be useful for further investigation of the mechanism of myo-inositol monophosphatase and for determination of whether inhibition of this enzyme plays a role in the therapeutic effectiveness of lithium in treatment of affective disorders.
K-76COONa是一种真菌产物，先前因其抑制补体激活而被分离出来，现已发现它能抑制肌醇单磷酸酶的活性。K-76COONa的效力略强于锂，其抑制常数（Ki）约为0.5 mM。以D-肌醇1-磷酸为底物进行动力学分析表明，K-76COONa对肌醇单磷酸酶的抑制作用相对于底物而言是非竞争性的，但与镁离子激活该酶的作用是竞争性的。抑制肌醇1,4-二磷酸/肌醇1,3,4-三磷酸1-磷酸酶对肌醇-[3H]1,4-二磷酸的水解作用需要更高浓度的K-76COONa（半数抑制浓度[IC50]约为7.5 mM）。K-76COONa可能有助于进一步研究肌醇单磷酸酶的作用机制，以及确定抑制该酶是否在锂盐治疗情感障碍的疗效中发挥作用。
