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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:KAPCG_HUMAN
Synonyms:
cAMP-dependent protein kinase catalytic subunit gamma
PKA C-gamma
EC-Numbers:2.7.11.11
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

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.