Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists

被引：87
|
作者：
Shen, Hong [1 ]
Maki, Carl G. [1 ]
机构：
[1] Rush Univ, Med Ctr, Dept Anat & Cell Biol, Chicago, IL 60612 USA
来源：
CURRENT PHARMACEUTICAL DESIGN | 2011年 / 17卷 / 06期
关键词：
Nutlin-3; p53; MDM2; therapy; NUTLIN-INDUCED APOPTOSIS; ACUTE MYELOID-LEUKEMIA; P53-MEDIATED MITOCHONDRIAL APOPTOSIS; ACUTE MYELOGENOUS LEUKEMIA; RING-FINGER DOMAIN; CELL-CYCLE ARREST; WILD-TYPE P53; MULTIPLE-MYELOMA; CANCER-CELLS; TUMOR-CELLS;
D O I：
10.2174/138161211795222603
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Restoring p53 activity by inhibiting the interaction between p53 and MDM2 represents an attractive approach for cancer therapy. To this end, a number of small-molecule p53-MDM2 binding inhibitors have been developed during the past several years. Nutlin-3 is a potent and selective small-molecule MDM2 antagonist that has shown considerable promise in pre-clinical studies. This review will highlight recent advances in the development of small-molecule MDM2 antagonists as potential cancer therapeutics, with special emphasis on Nutlin-3.
引用
收藏
页码：560 / 568
页数：9
相关论文
共 50 条
  • [1] In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Vassilev, LT
    Vu, BT
    Graves, B
    Carvajal, D
    Podlaski, F
    Filipovic, Z
    Kong, N
    Kammlott, U
    Lukacs, C
    Klein, C
    Fotouhi, N
    Liu, EA
    [J]. SCIENCE, 2004, 303 (5659) : 844 - 848
  • [2] Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy
    Tovar, C
    Rosinski, J
    Filipovic, Z
    Higgins, B
    Kolinsky, K
    Hilton, H
    Zhao, XL
    Vu, BT
    Qing, WG
    Packman, K
    Myklebost, O
    Heimbrook, DC
    Vassilev, LT
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (06) : 1888 - 1893
  • [3] Small molecule inhibitors of p53/MDM2 interaction
    Fotouhi, N
    Graves, B
    [J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2005, 5 (02) : 159 - 165
  • [4] Small-molecule antagonists of the p53-mdm2 interaction
    Vu, Binh T.
    Graves, Bradford
    Vassilev, Lyubomir T.
    Carvajal, Daisy
    Filipovic, Zoran
    Lukacs, Christine
    Klein, Christian
    Kammlott, Ursula
    Podlaski, Frank
    Qing, Weiguo
    Packman, Kathryn
    Kong, Norman
    Liu, Emily
    Dillon, Kathleen
    Specian, Anthony, Jr.
    Kaplan, Gerald
    So, Sung-Sau
    Emerson, Don
    Fry, David
    Kim, Kyungjin
    Mischke, Steven G.
    Wang, Bingbing
    Roberts, John
    Fotouhi, Nader
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 231
  • [5] Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials
    Haohao Zhu
    Hui Gao
    Yingying Ji
    Qin Zhou
    Zhiqiang Du
    Lin Tian
    Ying Jiang
    Kun Yao
    Zhenhe Zhou
    [J]. Journal of Hematology & Oncology, 15
  • [6] Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization
    Graves, Bradford
    Thompson, Thelma
    Xia, Mingxuan
    Janson, Cheryl
    Lukacs, Christine
    Deo, Dayanand
    Di Lello, Paola
    Fry, David
    Garvie, Colin
    Huang, Kuo-Sen
    Gao, Lin
    Tovar, Christian
    Lovey, Allen
    Wanner, Jutta
    Vassilev, Lyubomir T.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (29) : 11788 - 11793
  • [7] p53 and MDM2: Antagonists or Partners in Crime?
    Eischen, Christine M.
    Lozano, Guillermina
    [J]. CANCER CELL, 2009, 15 (03) : 161 - 162
  • [8] Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors
    Ivanenkov, Yan A.
    Vasilevski, Sergei V.
    Beloglazkina, Elena K.
    Kukushkin, Maksim E.
    Machulkin, Alexey E.
    Veselov, Mark S.
    Chufarova, Nina V.
    Chernyaginab, Elizaveta S.
    Vanzcool, Anton S.
    Zyk, Nikolay V.
    Skvortsov, Dmitry A.
    Khutornenko, Anastasia A.
    Rusanov, Alexander L.
    Tonevitsky, Alexander G.
    Dontsova, Olga A.
    Majouga, Alexander G.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (02) : 404 - 409
  • [9] Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule
    Grinkevich, Vera V.
    Vema, Aparna
    Fawkner, Karin
    Issaeva, Natalia
    Andreotti, Virginia
    Dickinson, Eleanor R.
    Hedstrom, Elisabeth
    Spinnler, Clemens
    Inga, Alberto
    Larsson, Lars-Gunnar
    Karlen, Anders
    Wilhelm, Margareta
    Barran, Perdita E.
    Okorokov, Andrei L.
    Selivanova, Galina
    Zawacka-Pankau, Joanna E.
    [J]. FRONTIERS IN MOLECULAR BIOSCIENCES, 2022, 9
  • [10] Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma
    Van Maerken, Tom
    Speleman, Frank
    Vermeulen, Joelle
    Lambertz, Irina
    De Clercq, Sarah
    De Smet, Els
    Yigit, Nurten
    Coppens, Vicky
    Philippe, Jan
    De Paepe, Anne
    Marine, Jean-Christophe
    Vandesompele, Jo
    [J]. CANCER RESEARCH, 2006, 66 (19) : 9646 - 9655
12345