In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems

被引：34

作者：

Beedie, Shaunna L. ^{[1
,2
]}

Rore, Holly M. ^{[1
]}

Barnett, Shelby ^{[1
,4
]}

Chau, Cindy H. ^{[2
]}

Luo, Weiming ^{[3
]}

Greig, Nigel H. ^{[3
]}

Figg, William D. ^{[2
]}

Vargesson, Neil ^{[1
]}

机构：

[1] Univ Aberdeen, Inst Med Sci, Sch Med Med Sci & Nutr, Foresterhill, Aberdeen, Scotland

[2] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA

[3] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA

[4] Univ Manchester, Manchester Pharm Sch, Ctr Appl Pharmacokinet Res, Manchester, Lancs, England

来源：

ONCOTARGET | 2016年 / 7卷 / 22期

基金：

英国惠康基金;

关键词：

angiogenesis; inflammation; thalidomide; cancer; teratogenesis; NECROSIS-FACTOR-ALPHA; REFRACTORY MULTIPLE-MYELOMA; TNF-ALPHA; SYNTHESIS INHIBITOR; TRANSGENIC ZEBRAFISH; COGNITIVE DEFICITS; ALZHEIMERS-DISEASE; LIMB DEFECTS; ANGIOGENESIS; POMALIDOMIDE;

D O I：

10.18632/oncotarget.8909

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Thalidomide, a drug known for its teratogenic side-effects, is used successfully to treat a variety of clinical conditions including leprosy and multiple myeloma. Intense efforts are underway to synthesize and identify safer, clinically relevant analogs. Here, we conduct a preliminary in vivo screen of a library of new thalidomide analogs to determine which agents demonstrate activity, and describe a cohort of compounds with anti-angiogenic properties, anti-inflammatory properties and some compounds which exhibited both. The combination of the in vivo zebrafish and chicken embryo model systems allows for the accelerated discovery of new, potential therapies for cancerous and inflammatory conditions.

引用

页码：33237 / 33245

页数：9

共 54 条

[21] A SHORT HISTORY OF THALIDOMIDE EMBRYOPATHY [J].

LENZ, W .

TERATOLOGY, 1988, 38 (03) :203-215

[22]

Lenz W., 1962, German Medical Monthly, V7, P253

[23] Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide [J].

Lopez-Girona, A. ;

Mendy, D. ;

Ito, T. ;

Miller, K. ;

Gandhi, A. K. ;

Kang, J. ;

Karasawa, S. ;

Carmel, G. ;

Jackson, P. ;

Abbasian, M. ;

Mahmoudi, A. ;

Cathers, B. ;

Rychak, E. ;

Gaidarova, S. ;

Chen, R. ;

Schafer, P. H. ;

Handa, H. ;

Daniel, T. O. ;

Evans, J. F. ;

Chopra, R. .

LEUKEMIA, 2012, 26 (11) :2326-2335

[24] Epidemiological Surveillance of Birth Defects Compatible with Thalidomide Embryopathy in Brazil [J].

Luiz Vianna, Fernanda Sales ;

Lopez-Camelo, Jorge S. ;

Louguercio Leite, Julio Cesar ;

Vieira Sanseverino, Maria Teresa ;

Dutra, Maria da Graca ;

Castilla, Eduardo E. ;

Schueler-Faccini, Lavinia .

PLOS ONE, 2011, 6 (07)

[25] Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro [J].

Mahony, Chris ;

Erskine, Lynda ;

Niven, Jennifer ;

Greig, Nigel H. ;

Figg, William Douglas ;

Vargesson, Neil .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (31) :12703-12708

[26] Thalidomide: A review of approved and investigational uses [J].

Matthews, SJ ;

McCoy, C .

CLINICAL THERAPEUTICS, 2003, 25 (02) :342-395

[27]

Miller MT, 1999, TERATOLOGY, V60, P306, DOI 10.1002/(SICI)1096-9926(199911)60:5<306::AID-TERA11>3.0.CO

[28]

2-Y

[29] THALIDOMIDE EXERTS ITS INHIBITORY-ACTION ON TUMOR-NECROSIS-FACTOR-ALPHA BY ENHANCING MESSENGER-RNA DEGRADATION [J].

MOREIRA, AL ;

SAMPAIO, EP ;

ZMUIDZINAS, A ;

FRINDT, P ;

SMITH, KA ;

KAPLAN, G .

JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (06) :1675-1680

[30] Thalidomide, an antiangiogenic agent with clinical activity in cancer [J].

Ng, SSW ;

Brown, M ;

Figg, WD .

BIOMEDICINE & PHARMACOTHERAPY, 2002, 56 (04) :194-199

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