A Screening Method for Potential Anti-pancreatic Cancer Candidate Compounds Based on Hsp90-Cdc37 Interaction Model in vitro

被引:0
作者
Zhang, Hai [1 ,2 ]
Sun, Sen [1 ]
Chen, Qingshan [1 ]
Zhang, Guoqing [1 ]
Zhang, Zhenqing
Sun, Duxin [2 ]
Zhang, Wenpeng [2 ,3 ]
机构
[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pharm, Shanghai 200438, Peoples R China
[2] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
[3] Beijing Inst Pharmacol & Toxicol, Key Lab Drug Metab & Pharmacokinet, Beijing 100850, Peoples R China
关键词
Anti-cancer; Cdc37; a screening method; Hsp90; Hsp90/Cdc37; interaction; protein interaction model in vitro; SRL-PFAC; PROTEIN-PROTEIN INTERACTIONS; COMPLEX; HSP90; INHIBITORS; DISCOVERY; RESIDUES; AGENTS; CDC37;
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The Hsp90/Cdc37 (heat shock protein 90; cell division cycle 37) interaction is a promising target for anti-cancer candidate drug development. The purpose of this research is to establish a screening method for anti-cancer candidate compounds based on the Hsp90/Cdc37 interaction model in vitro by Split Renilla luciferase protein fragment-assisted complementation bioluminescence technology. The parameters influencing the protein binding in this model were optimized, including protein concentration, reaction time, and substrate concentration. The optimal condition was as follows: protein concentration 2 mu M, the ratio of Hsp90 and Cdc37 1:1, reaction time 10 min, and the GLO (R) substrate (Promega, Madison, WI, USA) dilution 1:100. The screening model was further validated by some known compounds blocking the Hsp90/Cdc37 interactions. It was proved that this method is rapid and sensitive and could be used for screening of anti-pancreatic cancer candidate compounds.
引用
收藏
页码:66 / 71
页数:6
相关论文
共 27 条
  • [1] Molecular chaperones: Toward new therapeutic tools
    Almeida, Mauro B.
    Martins do Nascimento, Jose Luiz
    Herculano, Anderson Manoel
    Crespo-Lopez, Maria Elena
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2011, 65 (04) : 239 - 243
  • [2] Targeting apoptosis pathways in pancreatic cancer
    Arlt, Alexander
    Mueerkoester, Susanne Sebens
    Schaefer, Heiner
    [J]. CANCER LETTERS, 2013, 332 (02) : 346 - 358
  • [3] Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function
    Basso, AD
    Solit, DB
    Chiosis, G
    Giri, B
    Tsichlis, P
    Rosen, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) : 39858 - 39866
  • [4] Cell Surface Cdc37 Participates in Extracellular HSP90 Mediated Cancer Cell Invasion
    El Hamidieh, Avraam
    Grammatikakis, Nicholas
    Patsavoudi, Evangelia
    [J]. PLOS ONE, 2012, 7 (08):
  • [5] A proteomic approach towards the Hsp90-dependent ubiquitinylated proteome
    Falsone, S. Fabio
    Gesslbauer, Bernd
    Rek, Angelika
    Kungl, Andreas J.
    [J]. PROTEOMICS, 2007, 7 (14) : 2375 - 2383
  • [6] Discovery of BRM Targeted Therapies: Novel Reactivation of an Anticancer Gene
    Gramling, Sarah
    Reisman, David
    [J]. LETTERS IN DRUG DESIGN & DISCOVERY, 2011, 8 (01) : 93 - 99
  • [7] Discovery of small molecule cancer drugs: Successes, challenges and opportunities
    Hoelder, Swen
    Clarke, Paul A.
    Workman, Paul
    [J]. MOLECULAR ONCOLOGY, 2012, 6 (02) : 155 - 176
  • [8] Targeting the molecular chaperone heat shock protein 90 (HSP90): Lessons learned and future directions
    Hong, David S.
    Banerji, Udai
    Tavana, Bahareh
    George, Goldy C.
    Aaron, Joann
    Kurzrock, Razelle
    [J]. CANCER TREATMENT REVIEWS, 2013, 39 (04) : 375 - 387
  • [9] FW-04-806 inhibits proliferation and induces apoptosis in human breast cancer cells by binding to N-terminus of Hsp90 and disrupting Hsp90-Cdc37 complex formation
    Huang, Wei
    Ye, Min
    Zhang, Lian-ru
    Wu, Qun-dan
    Zhang, Min
    Xu, Jian-hua
    Zheng, Wei
    [J]. MOLECULAR CANCER, 2014, 13
  • [10] Synthesis and Anti-Cancer Activities of Aryl Benzyl Ethers with Fluoro Substituents
    Jiang, Yi
    Xu, Hong
    Liu, Li
    He, Rui
    Song, Xiaomei
    Li, Na
    [J]. LETTERS IN DRUG DESIGN & DISCOVERY, 2014, 11 (06) : 736 - 741