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Drug-Target Interaction

Drug

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PubChem ID:14978
Structure:
Synonyms:
1405-48-7
18417-89-5
18417-89-5 (FREE BASE)
21090-35-7 (HYDROCHLORIDE)
4-amino-5-carboxamido-7-(D-ribofuranosyl)-pyrrolo-(2,3-d)pyrimidine
4-Amino-7-beta-D-arabinofuranosyl-7H-pyrrolo(2,3-d)pyrimidine-5-carboxamid
4-Amino-7-beta-D-arabinofuranosyl-7H-pyrrolo(2,3-d)pyrimidine-5-carboxamide
4-Amino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)pyrimidine-5-carboxamide
7-Deazaadenosine-7-carboxamide
7H-Pyrrolo(2,3-d)pyrimidine-5-carboxamide, 4-amino-7-beta-D-arabinofuranosyl-
7H-Pyrrolo(2,3-d)pyrimidine-5-carboxamide, 4-amino-7-beta-D-ribofuranosyl-
7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide, 4-amino-7-.beta.-D-ribofuranosyl-
90813-74-4
AIDS-127104
AIDS127104
Antibiotic B 14437 (base)
Antibiotic B-14437
Ara-sangivamycin
B 90912
B-14437
BRN 0626355
BRN 4205613
C12H15N5O5
LS-139553
LS-139556
NSC 134339
NSC 65346
NSC-65346
NSC143648 (HYDROCHLORIDE)
NSC65346 (FREE BASE)
SANGIVAMYCIN
Sangivamycin, hydrochloride
Sanzivamycin
SKI 27013

Target

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Uniprot ID:ICE_DROME
Synonyms:
Caspase
drICE
EC-Numbers:3.4.22.-
Organism:Drosophila melanogaster
Fruit fly
PDB IDs:-

Binding Affinities:

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

References:

17371872
The nucleoside analog sangivamycin induces apoptotic cell death in breast carcinoma MCF7/adriamycin-resistant cells via protein kinase Cdelta and JNK activation.. Sung A Lee; Mira Jung (2007) The Journal of biological chemistry display abstract
Sangivamycin has shown a potent antiproliferative activity against a variety of human cancers. However, little is known about the mechanism of action underlying its antitumor activity. Here we demonstrate that sangivamycin has differential antitumor effects in drug-sensitive MCF7/wild type (WT) cells, causing growth arrest, and in multidrug-resistant MCF7/adriamycin-resistant (ADR) human breast carcinoma cells, causing massive apoptotic cell death. Comparisons between the effects of sangivamycin on these two cell lines allowed us to identify the mechanism underlying the apoptotic antitumor effect. Fluorescence-activated cell sorter analysis indicated that sangivamycin induced cell cycle arrest in the G(2)/M phase in MCF7/ADR cells. A marked induction of c-Jun expression as well as phosphorylation of c-Jun and JNK was observed after sangivamycin treatment of MCF7/ADR cells but not MCF7/WT cells. Sangivamycin also induced cleavage of lamin A and poly(ADP-ribose) polymerase (PARP) in MCF7/ADR cells, probably via activation of caspase-6, -7, and -9. Pretreatment with a caspase-9-specific inhibitor or pan-caspase inhibitor abolished sangivamycin-induced cleavage of lamin A and PARP but not sangivamycin induction of c-Jun expression and phosphorylation. Pretreatment of MCF7/ADR cells with SP600125, a specific inhibitor of JNK, or with rottlerin, a specific inhibitor of protein kinase Cdelta (PKCdelta), significantly reduced the sangivamycin-induced apoptosis and almost completely abolished sangivamycin-induced phosphorylation of c-Jun and cleavage of lamin A and PARP. Transfection of MCF7/ADR cells with PKCdelta small interfering RNAs or PKCdelta antibody or rottlerin pretreatment significantly suppressed the phosphorylation of JNK. Taken together, our data suggest that sangivamycin induces mitochondria-mediated apoptotic cell death of MCF7/ADR cells via activation of JNK in a protein kinase Cdelta-dependent manner.