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

[1] Transiently lowering tumor necrosis factor-α synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice [J].

Baratz, Renana ;

Tweedie, David ;

Wang, Jia-Yi ;

Rubovitch, Vardit ;

Luo, Weiming ;

Hoffer, Barry J. ;

Greig, Nigel H. ;

Pick, Chaim G. .

JOURNAL OF NEUROINFLAMMATION, 2015, 12

[2] Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent [J].

Bauer, KS ;

Dixon, SC ;

Figg, WD .

BIOCHEMICAL PHARMACOLOGY, 1998, 55 (11) :1827-1834

[3] Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues [J].

Beedie, Shaunna L. ;

Peer, Cody J. ;

Pisle, Steven ;

Gardner, Erin R. ;

Mahony, Chris ;

Barnett, Shelby ;

Ambrozak, Agnieszka ;

Guetschow, Michael ;

Chau, Cindy H. ;

Vargesson, Neil ;

Figg, William D. .

MOLECULAR CANCER THERAPEUTICS, 2015, 14 (10) :2228-2237

[4] TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation [J].

Belarbi, Karim ;

Jopson, Timothy ;

Tweedie, David ;

Arellano, Carla ;

Luo, Weiming ;

Greig, Nigel H. ;

Rosi, Susanna .

JOURNAL OF NEUROINFLAMMATION, 2012, 9

[5] Tumor-induced perturbations of cytokines and immune cell networks [J].

Burkholder, Brett ;

Huang, Ren-Yu ;

Burgess, Rob ;

Luo, Shuhong ;

Jones, Valerie Sloane ;

Zhang, Wenji ;

Lv, Zhi-Qiang ;

Gao, Chang-Yu ;

Wang, Bao-Ling ;

Zhang, Yu-Ming ;

Huang, Ruo-Pan .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2014, 1845 (02) :182-201

[6] Thalidomide: Current and potential clinical applications [J].

Calabrese, L ;

Fleischer, AB .

AMERICAN JOURNAL OF MEDICINE, 2000, 108 (06) :487-495

[7]

Castilla EE, 1996, TERATOLOGY, V54, P273, DOI 10.1002/(SICI)1096-9926(199612)54:6<273::AID-TERA1>3.0.CO

[8]

2-#

[9] The Distribution of Congenital Anomalies Within the VACTERL Association Among Tumor Necrosis Factor Antagonist-exposed Pregnancies Is Similar to the General Population [J].

Crijns, Hubertina J. M. J. ;

Jentink, Janneke ;

Garne, Ester ;

Gispen-de Wied, Christine C. ;

Straus, Sabine M. J. M. ;

de Jong-van den Berg, Lolkje T. W. .

JOURNAL OF RHEUMATOLOGY, 2011, 38 (09) :1871-1874

[10] THALIDOMIDE IS AN INHIBITOR OF ANGIOGENESIS [J].

DAMATO, RJ ;

LOUGHNAN, MS ;

FLYNN, E ;

FOLKMAN, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :4082-4085

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