de Witte P, Agostinis P, Van Lint J, Merlevede W, Vandenheede J R
Laboratorium voor Farmaceutische Biologie, Instituut voor Farmaceutische Wetenschappen, Leuven, Belgium.
Biochem Pharmacol. 1993 Dec 3;46(11):1929-36. doi: 10.1016/0006-2952(93)90633-8.
The naphthodianthrone hypericin produces a potent and irreversible inhibition of the epidermal growth factor (EGF) receptor tyrosine kinase activity. The inhibition was time and temperature dependent but did not depend on EGF activation. The IC50 values obtained were 0.37-8.7 microM with membranes incubated for 30 min at 30 degrees or 10 min at 0 degree, respectively. Kinetic analyses with poly(Glu,Ala,Tyr) 6:3:1 [poly(GAT)] as an exogenous substrate were in agreement with the irreversible nature of the inhibition. Irradiation for 30 min with fluorescent light caused a dramatic photosensitizing effect and resulted in an IC50 value of 44 nM. This effect was due to a type I mechanism, since the exclusion of oxygen did not alter the inhibition curve. The inhibition was inversely proportional to the amounts of membranes used, which probably reflects the non-specific sequestration of hypericin into the lipid bilayer. Ser/Thr protein kinases such as protein kinase A, casein kinase 1 and 2 and the enzyme 5'-nucleotidase, were not inhibited by hypericin not even at high concentrations (> 100 microM).
萘并二蒽酮金丝桃素对表皮生长因子（EGF）受体酪氨酸激酶活性产生强效且不可逆的抑制作用。这种抑制作用具有时间和温度依赖性，但不依赖于EGF激活。在30℃孵育30分钟或0℃孵育10分钟的膜上，获得的IC50值分别为0.37 - 8.7微摩尔。以聚（Glu，Ala，Tyr）6:3:1 [聚（GAT）]作为外源底物的动力学分析与抑制作用的不可逆性质一致。用荧光灯照射30分钟会产生显著的光敏效应，导致IC50值为44纳摩尔。这种效应是由于I型机制，因为排除氧气不会改变抑制曲线。抑制作用与所用膜的量成反比，这可能反映了金丝桃素非特异性地隔离到脂质双层中。丝氨酸/苏氨酸蛋白激酶，如蛋白激酶A、酪蛋白激酶1和2以及5'-核苷酸酶，即使在高浓度（>100微摩尔）下也不会被金丝桃素抑制。
