MDM2 Inhibitors for Pancreatic Cancer Therapy

被引:6
|
作者
Azmi, A. S. [2 ]
Philip, P. A.
Almhanna, K.
Beck, F. W. [2 ]
Kafri, Z. K. [2 ]
Sarkar, F. H. [2 ]
Mohammad, R. M. [1 ]
机构
[1] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Internal Med, Detroit, MI 48201 USA
[2] Wayne State Univ, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA
关键词
MDM2 and p53; small molecule inhibitors; pancreatic cancer; SMALL-MOLECULE INHIBITORS; CELL-CYCLE ARREST; WILD-TYPE P53; ACTIVATION; PATHWAY; SNP309; ANTAGONISTS; NUTLIN-3; TUMORS; DNA;
D O I
10.2174/138955710791384054
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
MDM2 protein negatively regulates p53 and is found to be elevated in cancer cells. An attractive approach towards targeting MDM2 is the use of small molecule inhibitors that bind to MDM2 and disrupt the MDM2-p53 interaction. Our laboratory has been at the forefront in testing MDM2 inhibitors in pancreatic adenocarcinoma (PaCa), a deadly disease with similar to 50% wild-type p53 population. Emerging evidence suggests that apart from regulating p53, MDM2 can influence other key molecules involved in cancer. This review summarizes recent advancements in the development of MDM2 inhibitors, their novel primary and secondary targets and highlights their potential as therapeutics for PaCa.
引用
收藏
页码:518 / 526
页数:9
相关论文
共 50 条
  • [31] Regiospecific synthesis of isoindolinones as MDM2 inhibitors
    Cully, Sarah J.
    Blackburn, Timothy J.
    Cano, Celine
    Golding, Bernard T.
    Griffin, Roger J.
    Lunec, John
    Newell, David
    Noble, Martin
    Zhao, Yan
    Hardcastle, Ian R.
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2013, 245
  • [32] P53 Mdm2 Inhibitors
    Khoury, Kareem
    Doemling, Alex
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2012, 18 (30) : 4668 - 4678
  • [33] Combination therapy with p53–MDM2 binding inhibitors for malignancies
    Zegao Jin
    Jianfeng Shen
    Jingyao He
    Chunqi Hu
    [J]. Medicinal Chemistry Research, 2015, 24 : 1369 - 1379
  • [34] Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer
    Bhatia, Neha
    Khator, Rakesh
    Kulkarni, Swanand
    Singh, Yogesh
    Kumar, Pradeep
    Thareja, Suresh
    [J]. CURRENT MEDICINAL CHEMISTRY, 2023, 30 (32) : 3668 - 3701
  • [35] MDM2 inhibitors sensitize testicular cancer models to mTORC1/2 inhibitors and cisplatin
    de Jong, Steven
    de Vries, Gerda
    Meersma, Gert Jan
    Suurmeijer, Albert J. H.
    van Vugt, Marcel A. T. M.
    Gietema, Jourik A.
    [J]. CANCER RESEARCH, 2020, 80 (16)
  • [36] MDM2, MDMX and p53 in oncogenesis and cancer therapy
    Mark Wade
    Yao-Cheng Li
    Geoffrey M. Wahl
    [J]. Nature Reviews Cancer, 2013, 13 : 83 - 96
  • [37] An overview of PROTACs targeting MDM2 as a novel approach for cancer therapy
    Li, Huiwen
    Cai, Xinhui
    Yang, Xiaoyu
    Zhang, Xuan
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 272
  • [38] The Roles of MDM2 and MDMX in Cancer
    Karni-Schmidt, Orit
    Lokshin, Maria
    Prives, Carol
    [J]. ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 11, 2016, 11 : 617 - 644
  • [39] MDM2, MDMX and p53 in oncogenesis and cancer therapy
    Wade, Mark
    Li, Yao-Cheng
    Wahl, Geoffrey M.
    [J]. NATURE REVIEWS CANCER, 2013, 13 (02) : 83 - 96
  • [40] MDM2 AND MDMX IN CANCER AND DEVELOPMENT
    Marine, Jean-Christophe
    [J]. CANCER AND DEVELOPMENT, 2011, 94 : 45 - 75