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Drug-Target Interaction

Drug

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PubChem ID:5281051
Structure:
Synonyms:
(component of) Hypericum spp (st. John's wort)
1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenanthro [1,10,9,8-opqra]perylene-7,14-dione P-conformer
1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenanthro(1,10,9,8-opqra)perylene-
1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenanthro(1,10,9,8-opqra)perylene-7,14-dione
1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione
1:6:8:10:11:13-hexahydroxy-3:4-dimethyl-meso-naphthodianthrene-7:14-dione
4,5,7,4',5',7'-Hexahydroxy-2,2'-dimethyl-mesonapthtodianthron
4,5,7,4',5',7'-Hexahydroxy-2,2'-dimethylnaphthodianthrone
548-04-9
56690_FLUKA
56690_SIGMA
AIDS-000117
AIDS-052002
AIDS000117
AIDS052002
Ambap348
BiomolKI2_000040
BiomolKI_000032
C07606
C30H16O8
CHEBI:5835
Cyclo werrol
Cyclo-Werol
Cyclosan
DRG-0113
EINECS 208-941-0
hipericina
HSCI1_000202
Hypericin
Hypericin & Visible light
Hypericin from Hypericum perforatum
hypericine
Hypericum Extract
Hypericum red
Hyperizin
LMPK13040001
LS-175574
NCGC00162454-01
NCGC00163378-01
NCI60_003879
NCI60_006799
NSC 407313
NSC 622946
NSC407313
NSC622946
phenanthro[1,10,9,8-opqra]perylene-7,14-dione, 1,3,4,6,8,13-hexahydroxy-10,11-dimethyl-
Phenanthro[1,10,9,8-opqra]perylene-7,14-dione,1,3,4,6,8,13-hexahydroxy-10,11-dimethyl-, stereoisomer
VIMRxyn
ZINC03780340

Target

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Uniprot ID:KPC3_DROME
Synonyms:
dPKC98F
PKC
Protein kinase C
EC-Numbers:2.7.11.13
Organism:Drosophila melanogaster
Fruit fly
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----

References:

7487096
Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent.. T Nishiuchi; T Utsumi; T Kanno; Y Takehara; H Kobuchi; T Yoshioka; A A Horton; T Yasuda; K Utsumi (1995) Archives of biochemistry and biophysics display abstract
We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide (O2.-) generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herb Hypericin triquetrifolium Turra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on stimulation-dependent O2.- generation and related enzymes of neutrophils were investigated. Hypericin inhibited O2.- generation of neutrophils induced by PKC-dependent and -independent stimuli in a light- and concentration-dependent manner. Oxygen was required for the light-dependent inhibition by hypericin. NADPH oxidase activity in a cell-free system and TNF-alpha-induced tyrosyl phosphorylation of neutrophil proteins were also inhibited by hypericin in a concentration- and light-dependent manner. However, tyrosine kinase of p60src, an enzyme not bound to a membrane, was not inhibited either in the light or in the dark. Oxygen uptake of neutrophils by photosensitization with hypericin resulted in the formation of singlet oxygen (1O2), O2.-, and hydroxyl radical (.OH) and enhanced lipid peroxidation. The formation of 1O2 was inhibited by azide, a quencher of 1O2, but not by desferrioxamine (DSF), a ferric ion chelator. By contrast, both generation of .OH and lipid peroxidation were inhibited by DSF but not by azide. Furthermore, PMA-induced O2.- generation inhibited by hypericin partially recovered in the presence of azide but not DSF. These results suggested that the light-dependent inhibition of O2.- generation by hypericin might be due to inhibition of tyrosine kinase, PKC, and NADPH oxidase via an oxygen-dependent mechanism, possibly through both Type I and II photosensitization mechanisms.
7511048
Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C.. W D Jarvis; A J Turner; L F Povirk; R S Traylor; S Grant (1994) Cancer research display abstract
The present studies were undertaken to characterize further the potential role of protein kinase C (PKC) in the regulation of apoptosis in HL-60 promyelocytic leukemia cells. The capacity of acute exposure to specific and nonspecific pharmacological inhibitors of PKC to promote apoptotic DNA fragmentation was examined both quantitatively and qualitatively and correlated with effects on cellular differentiation and proliferation. Incubation of HL-60 cells for 6 h with chelerythrine and calphostin C (highly specific inhibitors that act at the regulatory domain) or H7 and gossypol (nonspecific inhibitors that act at the PKC catalytic domain) produced concentration-dependent increases in DNA fragmentation. Induction of DNA fragmentation by chelerythrine, calphostin C, and gossypol was biphasic, resulting in a sharp decline in effect at concentrations above 5 microM, 0.1 microM, and 100 microM, respectively, whereas maximal and more stable effects were observed in response to H7 (100 microM). A 6-h exposure to staurosporine, a nonspecific but potent PKC inhibitor, failed to induce DNA fragmentation at concentrations generally used to achieve maximal inhibition of enzyme activity (e.g., 50 nM) but promoted fragmentation at considerably higher concentrations (e.g., > or = 200 nM). In contrast, 6-h exposures to the nonspecific protein kinase inhibitor hypericin (0.1 to 100 microM) or to the nonspecific inhibitor of protein kinase A, HA1004 (50 microM), were without effect on DNA fragmentation. DNA obtained from cells exposed to chelerythrine (5 microM), calphostin C (100 nM), H7 (50 microM), gossypol (50 microM), and staurosporine (200 nM)--but not hypericin (25 microM)--exhibited clear evidence of internucleosomal DNA cleavage on agarose gel electrophoresis; moreover, these cells exhibited the classical morphological features of apoptosis (cell shrinkage, nuclear condensation, and the formation of apoptotic bodies). All of the PKC inhibitors that induced apoptosis, and one of the inhibitors that did not (hypericin), substantially inhibited HL-60 cell clonogenicity at the concentrations evaluated. None of the agents tested induced cellular maturation as assessed by nonspecific esterase and nitro-blue tetrazolium positivity. DNA fragments obtained from cells exposed to specific and nonspecific PKC inhibitors possessed predominantly 5'-phosphate termini, consistent with the action of a Ca(2+)-/Mg(2+)-dependent endonuclease. Finally, Northern blot analysis revealed that exposure to calphostin C at a concentration that induced apoptosis (100 nM) failed to alter expression of bcl-2, an oncogene known to block apoptosis in both lymphoid and myeloid leukemia cells.