Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.


:In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.


Bioorg Med Chem Lett


Brabez N,Nguyen KL,Saunders K,Lacy R,Xu L,Gillies RJ,Lynch RM,Chassaing G,Lavielle S,Hruby VJ




Has Abstract


2013-04-15 00:00:00














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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Macreadie P,Avery T,Greatrex B,Taylor D,Macreadie I

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  • Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes.

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    pub_type: 杂志文章


    authors: Wilson JE,Kurukulasuriya R,Sinz C,Lombardo M,Bender K,Parker D,Sherer EC,Costa M,Dingley K,Li X,Mitelman S,Tong S,Bugianesi R,Ehrhardt A,Priest B,Ratliff K,Ujjainwalla F,Nargund R,Hagmann WK,Edmondson S

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hada N,Nakashima T,Shrestha SP,Masui R,Narukawa Y,Tani K,Takeda T

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  • Small molecule alteration of RNA sequence in cells and animals.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nankervis JL,Feil SC,Hancock NC,Zheng Z,Ng HL,Morton CJ,Holien JK,Ho PW,Frazzetto MM,Jennings IG,Manallack DT,Martin TJ,Thompson PE,Parker MW

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shin SY,Ahn S,Yoon H,Jung H,Jung Y,Koh D,Lee YH,Lim Y

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liang H,Tong WY,Zhao YY,Cui JR,Tu GZ

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Narayanaswamy N,Unnikrishnan M,Gupta M,Govindaraju T

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Khadikar PV,Singh S,Jaiswal M,Mandloi D

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cuny GD,Yu PB,Laha JK,Xing X,Liu JF,Lai CS,Deng DY,Sachidanandan C,Bloch KD,Peterson RT

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Saha AK,Liu L,Marichal P,Odds F

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Iserloh U,Wu Y,Cumming JN,Pan J,Wang LY,Stamford AW,Kennedy ME,Kuvelkar R,Chen X,Parker EM,Strickland C,Voigt J

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chang DJ,Kim WJ

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

    更新日期:2011-05-01 00:00:00