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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes

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Autor(es):
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Lanaro, Carolina [1] ; Franco-Penteado, Carla F. [1] ; Silva, Fabio H. [1] ; Fertrin, Kleber Y. [1, 2] ; dos Santos, Jean Leandro [3] ; Wade, Marlene [4] ; Yerigenahally, Shobha [4] ; de Melo, Thais R. [3] ; Chin, Chung Man [3] ; Kutlar, Abdullah [5] ; Meiler, Steffen E. [4] ; Costa, Fernando Ferreira [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil
[2] Univ Campinas UNICAMP, Sch Med, Dept Clin Pathol, Campinas, SP - Brazil
[3] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara - Brazil
[4] Augusta Univ, Dept Anesthesiol & Perioperat Med, Augusta, GA - USA
[5] Augusta Univ, Med Coll Georgia, Dept Med, Augusta, GA - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Experimental Hematology; v. 58, p. 35-38, FEB 2018.
Citações Web of Science: 2
Resumo

Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties. (C) 2018 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 08/57441-0 - Alterações clínicas, celulares e moleculares nas hemoglobinopatias e em outras anemias hemolíticas hereditárias
Beneficiário:Fernando Ferreira Costa
Linha de fomento: Auxílio à Pesquisa - Temático