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

Carolina Lanaro; Carla F. Franco-Penteado; Fabio H. Silva; Kleber Y. Fertrin; Jean Leandro dos Santos; Marlene Wade; Shobha Yerigenahally; Thais R. de Melo; Chung Man Chin; Abdullah Kutlar; Steffen E. Meiler; Fernando Ferreira Costa

doi:10.1016/j.exphem.2017.10.003

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

Carolina Lanaro, Carla F. Franco-Penteado, Fabio H. Silva, Kleber Y. Fertrin, Jean Leandro dos Santos, Marlene Wade, Shobha Yerigenahally, Thais R. de Melo, Chung Man Chin, Abdullah Kutlar, Steffen E. Meiler, Fernando Ferreira Costa

Pulmonary Disease

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	35-38
Number of pages	4
Journal	Experimental Hematology
Volume	58
DOIs	https://doi.org/10.1016/j.exphem.2017.10.003
State	Published - Feb 2018

ASJC Scopus subject areas

Molecular Biology
Hematology
Genetics
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.exphem.2017.10.003

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Lanaro, C., Franco-Penteado, C. F., Silva, F. H., Fertrin, K. Y., dos Santos, J. L., Wade, M., Yerigenahally, S., de Melo, T. R., Chin, C. M., Kutlar, A., Meiler, S. E., & Costa, F. F. (2018). A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes. Experimental Hematology, 58, 35-38. https://doi.org/10.1016/j.exphem.2017.10.003

Lanaro, C, Franco-Penteado, CF, Silva, FH, Fertrin, KY, dos Santos, JL, Wade, M, Yerigenahally, S, de Melo, TR, Chin, CM, Kutlar, A , Meiler, SE & Costa, FF 2018, 'A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes', Experimental Hematology, vol. 58, pp. 35-38. https://doi.org/10.1016/j.exphem.2017.10.003

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title = "A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes",

abstract = "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.",

author = "Carolina Lanaro and Franco-Penteado, {Carla F.} and Silva, {Fabio H.} and Fertrin, {Kleber Y.} and {dos Santos}, {Jean Leandro} and Marlene Wade and Shobha Yerigenahally and {de Melo}, {Thais R.} and Chin, {Chung Man} and Abdullah Kutlar and Meiler, {Steffen E.} and Costa, {Fernando Ferreira}",

note = "Publisher Copyright: {\textcopyright} 2018 ISEH – Society for Hematology and Stem Cells",

year = "2018",

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doi = "10.1016/j.exphem.2017.10.003",

language = "English (US)",

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AU - Lanaro, Carolina

AU - Franco-Penteado, Carla F.

AU - Silva, Fabio H.

AU - Fertrin, Kleber Y.

AU - dos Santos, Jean Leandro

AU - Wade, Marlene

AU - Yerigenahally, Shobha

AU - de Melo, Thais R.

AU - Chin, Chung Man

AU - Kutlar, Abdullah

AU - Meiler, Steffen E.

AU - Costa, Fernando Ferreira

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

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

Abstract

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UN SDGs

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