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Drug-Target Interaction

Drug

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PubChem ID:3218
Structure:
Synonyms:
2,5-Cyclohexadiene-1,4-dione, 2,5-dihydroxy-3-undecyl-
2,5-Cyclohexadiene-1,4-dione, 2,5-dihydroxy-3-undecyl- (9CI)
2,5-dihydroxy-3-undecyl-1,4-benzochinon
2,5-Dihydroxy-3-undecyl-1,4-benzoquinone
2,5-Dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-dione
2,5-Dihydroxy-3-undecyl-p-benzoquinone
2,5-Dihydroxy-3-undecyl-[1,4]benzoquinone
2,5-dihydroxy-3-undecylcyclohexa-2,5-diene-1,4-dione
4-08-00-02769 (Beilstein Handbook Reference)
550-24-3
AC-542/20644009
AC1L1FFT
AC1Q6BUE
AIDS-009914
AIDS009914
Apoptosis Activator III, Embelin
AR-1D4332
BIDD:ER0529
BRN 1885786
BSPBio_003531
C010945
C10342
C17H26O4
CCG-39906
CHEBI:229472
CHEMBL221137
DivK1c_006597
E1406_SIGMA
EINECS 208-979-8
Embelic acid
Embelin
Embelin, Embelia ribes
Emberine
HMS1922B07
HMS2271A03
HSCI1_000123
KBio1_001541
KBio2_001993
KBio2_004561
KBio2_007129
KBio3_002783
KBioGR_002240
KBioSS_001993
LS-40347
MLS000563189
MolPort-000-165-323
NCGC00017248-01
NCGC00017248-02
NCGC00017248-03
NCGC00017248-04
NCGC00017248-05
NCGC00017248-06
NCGC00017248-07
NCGC00017248-08
NCGC00025359-01
NCGC00025359-02
NCGC00025359-03
NCGC00025359-04
NCGC00025359-05
NCI60_042031
NSC 91874
NSC91874
p-Benzoquinone, 2,5-dihydroxy-3-undecyl-
potassium embelate
SBB005949
SDCCGMLS-0066817.P001
SMR000470851
SpecPlus_000501
SPECTRUM1504074
Spectrum3_001931
Spectrum4_001760
Spectrum5_000620
Spectrum_001513
ST057212
TNP00137
Tocris-2156
XIAP inhibitor, Embelin

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:

15115387
Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database.. Zaneta Nikolovska-Coleska; Liang Xu; Zengjian Hu; York Tomita; Peng Li; Peter P Roller; Renxiao Wang; Xueliang Fang; Ribo Guo; Manchao Zhang; Marc E Lippman; Dajun Yang; Shaomeng Wang (2004) Journal of medicinal chemistry display abstract
The X-linked inhibitor of apoptosis (XIAP) is a promising new molecular target for the design of novel anticancer drugs aiming at overcoming apoptosis-resistance of cancer cells to chemotherapeutic agents and radiation therapy. Recent studies demonstrated that the BIR3 domain of XIAP where caspase-9 and Smac proteins bind is an attractive site for designing small-molecule inhibitors of XIAP. Through computational structure-based screening of an in-house traditional herbal medicine three-dimensional structure database of 8221 individual natural products, followed by biochemical testing of selected candidate compounds, we discovered embelin from the Japanese Ardisia herb as a small-molecular weight inhibitor that binds to the XIAP BIR3 domain. We showed that embelin binds to the XIAP BIR3 protein with an affinity similar to that of the natural Smac peptide using a fluorescence polarization-based binding assay. Our NMR analysis further conclusively confirmed that embelin interacts with several crucial residues in the XIAP BIR3 domain with which Smac and caspsase-9 bind. Embelin inhibits cell growth, induces apoptosis, and activates caspase-9 in prostate cancer cells with high levels of XIAP, but has a minimal effect on normal prostate epithelial and fibroblast cells with low levels of XIAP. In stably XIAP-transfected Jurkat cells, embelin effectively overcomes the protective effect of XIAP to apoptosis and enhances the etoposide-induced apoptosis and has a minimal effect in Jurkat cells transfected with vector control. Taken together, our results showed that embelin is a fairly potent, nonpeptidic, cell-permeable, small-molecule inhibitor of XIAP and represents a promising lead compound for designing an entirely new class of anticancer agents that target the BIR3 domain of XIAP.