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PDBsum entry 3f7h
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References listed in PDB file
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Key reference
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Title
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Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.
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Authors
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F.Cohen,
B.Alicke,
L.O.Elliott,
J.A.Flygare,
T.Goncharov,
S.F.Keteltas,
M.C.Franklin,
S.Frankovitz,
J.P.Stephan,
V.Tsui,
D.Vucic,
H.Wong,
W.J.Fairbrother.
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Ref.
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J Med Chem, 2009,
52,
1723-1730.
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PubMed id
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Abstract
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A series of IAP antagonists based on an azabicyclooctane scaffold was designed
and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3
domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values
of 140, 38, and 33 nM, respectively. These compounds promote degradation of
c-IAP1, activate caspases, and lead to decreased viability of breast cancer
cells without affecting normal mammary epithelial cells. Finally, compound 14b
inhibits tumor growth when dosed orally in a breast cancer xenograft model.
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Secondary reference #1
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Title
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Design, Synthesis, And biological activity of a potent smac mimetic that sensitizes cancer cells to apoptosis by antagonizing iaps.
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Authors
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K.Zobel,
L.Wang,
E.Varfolomeev,
M.C.Franklin,
L.O.Elliott,
H.J.Wallweber,
D.C.Okawa,
J.A.Flygare,
D.Vucic,
W.J.Fairbrother,
K.Deshayes.
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Ref.
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Acs Chem Biol, 2006,
1,
525-533.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Engineering ml-Iap to produce an extraordinarily potent caspase 9 inhibitor: implications for smac-Dependent anti-Apoptotic activity of ml-Iap.
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Authors
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D.Vucic,
M.C.Franklin,
H.J.Wallweber,
K.Das,
B.P.Eckelman,
H.Shin,
L.O.Elliott,
S.Kadkhodayan,
K.Deshayes,
G.S.Salvesen,
W.J.Fairbrother.
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Ref.
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Biochem J, 2005,
385,
11-20.
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PubMed id
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Secondary reference #3
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Title
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Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ml-Iap).
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Authors
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M.C.Franklin,
S.Kadkhodayan,
H.Ackerly,
D.Alexandru,
M.D.Distefano,
L.O.Elliott,
J.A.Flygare,
G.Mausisa,
D.C.Okawa,
D.Ong,
D.Vucic,
K.Deshayes,
W.J.Fairbrother.
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Ref.
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Biochemistry, 2003,
42,
8223-8231.
[DOI no: ]
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PubMed id
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