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Small-molecule Antagonists Of Apoptosis Suppressor XIAP Exhibit Broad Antitumor Activity.

A. Schimmer, K. Welsh, C. Pinilla, Zhiliang Wang, M. Krajewska, Marie-Josee Bonneau, I. Pedersen, S. Kitada, F. Scott, B. Bailly-Maître, G. Glinsky, D. Scudiero, E. Sausville, G. Salvesen, A. Nefzi, J. Ostresh, R. Houghten, John Calvin Reed
Published 2004 · Biology, Medicine

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Apoptosis resistance commonly occurs in cancers, preventing activation of Caspase family cell death proteases. XIAP is an endogenous inhibitor of Caspases overexpressed in many cancers. We developed an enzyme derepression assay, based on overcoming XIAP-mediated suppression of Caspase-3, and screened mixture-based combinatorial chemical libraries for compounds that reversed XIAP-mediated inhibition of Caspase-3, identifying a class of polyphenylureas with XIAP-inhibitory activity. These compounds, but not inactive structural analogs, stimulated increases in Caspase activity, directly induced apoptosis of many types of tumor cell lines in culture, and sensitized cancer cells to chemotherapeutic drugs. Active compounds also suppressed growth of established tumors in xenograft models in mice, while displaying little toxicity to normal tissues. These findings validate IAPs as targets for cancer drug discovery.
This paper references
Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.
M. Alley (1988)
Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries.
C. Pinilla (1992)
10.1073/PNAS.91.23.11138
"Libraries from libraries": chemical transformation of combinatorial libraries to extend the range and repertoire of chemical diversity.
J. Ostresh (1994)
10.1074/jbc.272.12.7797
Target Protease Specificity of the Viral Serpin CrmA
Q. Zhou (1997)
10.1038/40901
X-linked IAP is a direct inhibitor of cell-death proteases
Q. Deveraux (1997)
10.1093/emboj/16.23.6914
The c‐IAP‐1 and c‐IAP‐2 proteins are direct inhibitors of specific caspases
N. Roy (1997)
10.1074/jbc.272.41.25719
Biochemical Characteristics of Caspases-3, -6, -7, and -8*
H. Stennicke (1997)
10.1074/JBC.273.14.7787
A Single BIR Domain of XIAP Sufficient for Inhibiting Caspases*
R. Takahashi (1998)
10.1126/SCIENCE.281.5381.1305
Death receptors: signaling and modulation.
A. Ashkenazi (1998)
10.1093/emboj/17.8.2215
IAPs block apoptotic events induced by caspase‐8 and cytochrome c by direct inhibition of distinct caspases
Q. Deveraux (1998)
10.1126/SCIENCE.281.5381.1312
Caspases: enemies within.
N. Thornberry (1998)
10.1101/GAD.12.11.1551
Proteases to die for.
V. Cryns (1998)
10.1074/jbc.274.13.8359
Caspase-9 Can Be Activated without Proteolytic Processing*
H. Stennicke (1999)
10.1093/emboj/18.19.5242
Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases
Q. Deveraux (1999)
10.1038/44617
NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP
C. Sun (1999)
10.1073/PNAS.040469797
The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury.
M. Holcik (2000)
10.1038/35050012
Structural basis of IAP recognition by Smac/DIABLO
G. Wu (2000)
10.1016/S0040-4039(00)00845-5
An efficient two-step synthesis of mono-, di- and triureas from resin-bound amides
A. Nefzi (2000)
Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.
I. Tamm (2000)
10.1038/35050006
Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain
Z. Liu (2000)
Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells.
H. Sasaki (2000)
10.1128/MCB.21.10.3604-3608.2001
Characterization of XIAP-Deficient Mice
H. Harlin (2001)
10.1038/35065125
A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis
S. Srinivasula (2001)
10.1038/35077213
Proliferation, cell cycle and apoptosis in cancer
G. Evan (2001)
10.1016/S0092-8674(01)00274-4
Structural Basis for the Inhibition of Caspase-3 by XIAP
S. Riedl (2001)
10.1023/A:1011167113067
Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients.
C. G. Ferreira (2001)
10.1016/S1097-2765(01)00341-0
A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
Y. Suzuki (2001)
10.1038/35055027
Identification of XAF1 as an antagonist of XIAP anti-Caspase activity
P. Liston (2001)
10.1038/35068604
Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex
G. Xu (2001)
Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications.
J. Dimitroulakos (2001)
10.1172/JCI14123
The Survivin saga goes in vivo.
John Calvin Reed (2001)
10.1038/nm735
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo
S. Fulda (2002)
10.1074/jbc.M112045200
SMAC Negatively Regulates the Anti-apoptotic Activity of Melanoma Inhibitor of Apoptosis (ML-IAP)*
D. Vucic (2002)
10.1016/S0968-0004(01)02045-X
Reprieval from execution: the molecular basis of caspase inhibition.
H. Stennicke (2002)
10.1182/BLOOD.V99.3.1038
The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction.
J. Byrd (2002)
10.1007/s00432-002-0364-z
Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer
H. Hofmann (2002)
10.1093/CARCIN/23.6.1017
Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma.
G. Gordon (2002)
Elevated expression of inhibitor of apoptosis proteins in prostate cancer.
M. Krajewska (2003)
10.1002/ijc.10776
Role of XIAP in the malignant phenotype of transitional cell cancer (TCC) and therapeutic activity of XIAP antisense oligonucleotides against multidrug‐resistant TCC in vitro
V. Bilim (2003)
Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy.
Lily Yang (2003)
Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy.
A. Schimmer (2003)
10.1016/S1074-5521(03)00157-1
Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction.
T. Wu (2003)
10.1038/nm0103-118
Advances in the use of synthetic combinatorial chemistry: Mixture-based libraries
C. Pinilla (2003)
Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide.
L. Yang (2003)
10.1093/emboj/cdg263
HBXIP functions as a cofactor of survivin in apoptosis suppression
H. Marusawa (2003)



This paper is referenced by
OTT_A_282334 301..314
Fanfan Zhu (2021)
10.1371/journal.pone.0248175
Induction of interferon-β and interferon signaling by TRAIL and Smac mimetics via caspase-8 in breast cancer cells
Victoria Granqvist (2021)
10.2147/OTT.S282334
Physalis alkekengi var. franchetii Extracts Exert Antitumor Effects on Non-Small Cell Lung Cancer and Multiple Myeloma by Inhibiting STAT3 Signaling
Yufei Fu (2021)
10.3390/cells9020406
Future Therapeutic Directions for Smac-Mimetics
Emma Morrish (2020)
10.1080/07391102.2020.1713892
Molecular basis of SMAC-XIAP binding and the effect of electrostatic polarization
Shuaizhen Tian (2020)
10.1016/j.ijpharm.2020.119535
Apoptosis-inducing Peptide Loaded in PLGA Nanoparticles Induces Anti-tumor Effects In Vivo.
D. Priwitaningrum (2020)
10.2174/1568009620666200720011341
Molecular Dynamics in Esophageal Adenocarcinoma: Who's in Control?
Tong Dang (2020)
10.18725/OPARU-25310
Sensitization of pancreatic carcinoma cells for chemotherapy-induced apoptosis using small-molecule inhibitors of X-linked inhibitor of apoptosis protein (XIAP)
Marc Reiser (2020)
10.1007/s00109-020-01977-w
Targeting X chromosome-linked inhibitor of apoptosis protein in mucoepidermoid carcinoma of the head and neck: A novel therapeutic strategy using nitidine chloride.
Hye-Jeong Kwon (2020)
The Mechanism of Caspase-8-Mediated Gene Expression and Its Integral Role in Host Defense
Alexandra Delaney (2019)
10.1016/J.DDTEC.2018.12.002
SNIPERs-Hijacking IAP activity to induce protein degradation.
M. Naito (2019)
10.1158/1078-0432.CCR-18-3802
Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPV− and HPV+ Head and Neck Cancers to TNFα, TRAIL, and Radiation Therapy
R. Xiao (2019)
10.3892/ijo.2018.4637
Fe3O4-solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells
Xiao-dong Xie (2019)
10.1007/s00262-019-02370-4
Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade
J. Zhou (2019)
10.1016/j.csbj.2019.01.009
Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment
F. Cossu (2019)
10.3390/cancers11091336
XIAP as a Target of New Small Organic Natural Molecules Inducing Human Cancer Cell Death
Diego Muñoz (2019)
10.1093/toxsci/kfy307
The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells
Zhi-Guo Sheng (2019)
10.1002/jcb.28205
Smac mimetics as novel promising modulators of apoptosis in the treatment of breast cancer
A. Nikkhoo (2019)
10.1002/jcb.26848
Calmodulin antagonist enhances DR5‐mediated apoptotic signaling in TRA‐8 resistant triple negative breast cancer cells
Romone M. Fancy (2018)
Bacteria-Mediated Delivery of mazF mRNA into Cancer Cells for Induction of Apoptosis
M. S. A. Zadeh (2018)
10.1016/j.biopha.2018.08.065
The role of XIAP in resistance to TNF-related apoptosis-inducing ligand (TRAIL) in Leukemia.
R. Saraei (2018)
10.17576/JSM-2018-4711-15
More ulam for your brain: a review on the potential role of ulam in protecting against cognitive decline
Y. You (2018)
10.1186/s13045-017-0470-7
Current status and perspectives of patient-derived xenograft models in cancer research
Y. Lai (2017)
10.7282/T31G0Q4Q
Understanding the role of the PALB2-BRCA1 interaction in tumor suppression
A. Mahdi (2017)
10.1016/j.biopha.2017.07.063
Role of GAB1/PI3K/AKT signaling high glucose-induced cardiomyocyte apoptosis.
D. Su (2017)
10.1371/journal.pone.0180895
Targeting of X-linked inhibitor of apoptosis protein and PI3-kinase/AKT signaling by embelin suppresses growth of leukemic cells
K. Prabhu (2017)
10.1016/j.yexcr.2017.10.015
CCN1 sensitizes esophageal cancer cells to TRAIL‐mediated apoptosis
Tong Dang (2017)
Development of novel anticancer agents for protein targets
N. E. Ortiz (2017)
10.13023/ETD.2017.290
DISCOVERING A NOVEL ANTIFUNGAL TARGET IN DOWNSTREAM STEROL BIOSYNTHESIS USING A SQUALENE SYNTHASE FUNCTIONAL MOTIF
Kristin B Linscott (2017)
10.1016/bs.apcsb.2016.10.003
Transcription Factors in Breast Cancer-Lessons From Recent Genomic Analyses and Therapeutic Implications.
E. Zacksenhaus (2017)
10.1159/000450825
The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats
Wencheng Zheng (2016)
10.1002/jbm.b.33545
Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.
P. Pofali (2016)
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