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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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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]
Total Authors: 12
[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
Total Affiliations: 5
Document type: Journal article
Source: Experimental Hematology; v. 58, p. 35-38, FEB 2018.
Web of Science Citations: 2

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)

FAPESP's process: 08/57441-0 - Clinical, cellular and molecular alterations in hemoglobinopathies and other hereditary hemolytic anemias
Grantee:Fernando Ferreira Costa
Support type: Research Projects - Thematic Grants