Hdl Handle:
http://hdl.handle.net/10675.2/793
Title:
FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors
Authors:
Makala, Levi HC; Di Maro, Salvatore; Lou, Tzu-Fang; Sivanand, Sharanya; Ahn, Jung-Mo; Pace, Betty S.
Abstract:
Fetal hemoglobin (HbF) improves the clinical severity of sickle cell disease (SCD), therefore, research to identify HbF-inducing agents for treatment purposes is desirable. The focus of our study is to investigate the ability of FK228 analogues to induce HbF using a novel KU812 dual-luciferase reporter system. Molecular modeling studies showed that the structure of twenty FK228 analogues with isosteric substitutions did not disturb the global structure of the molecule. Using the dual-luciferase system, a subgroup of FK228 analogues was shown to be inducers of HbF at nanomolar concentrations. To determine the physiological relevance of these compounds, studies in primary erythroid progenitors confirmed that JMA26 and JMA33 activated HbF synthesis at levels comparable to FK228 with low cellular toxicity. These data support our lead compounds as potential therapeutic agents for further development in the treatment of SCD.
Citation:
Anemia. 2012 May 14; 2012:428137
Issue Date:
14-May-2012
URI:
http://hdl.handle.net/10675.2/793
DOI:
10.1155/2012/428137
PubMed ID:
22655179
PubMed Central ID:
PMC3359661
Type:
Article
ISSN:
2090-1275
Appears in Collections:
Department of Pediatrics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorMakala, Levi HCen_US
dc.contributor.authorDi Maro, Salvatoreen_US
dc.contributor.authorLou, Tzu-Fangen_US
dc.contributor.authorSivanand, Sharanyaen_US
dc.contributor.authorAhn, Jung-Moen_US
dc.contributor.authorPace, Betty S.en_US
dc.date.accessioned2012-10-26T20:30:45Z-
dc.date.available2012-10-26T20:30:45Z-
dc.date.issued2012-05-14en_US
dc.identifier.citationAnemia. 2012 May 14; 2012:428137en_US
dc.identifier.issn2090-1275en_US
dc.identifier.pmid22655179en_US
dc.identifier.doi10.1155/2012/428137en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/793-
dc.description.abstractFetal hemoglobin (HbF) improves the clinical severity of sickle cell disease (SCD), therefore, research to identify HbF-inducing agents for treatment purposes is desirable. The focus of our study is to investigate the ability of FK228 analogues to induce HbF using a novel KU812 dual-luciferase reporter system. Molecular modeling studies showed that the structure of twenty FK228 analogues with isosteric substitutions did not disturb the global structure of the molecule. Using the dual-luciferase system, a subgroup of FK228 analogues was shown to be inducers of HbF at nanomolar concentrations. To determine the physiological relevance of these compounds, studies in primary erythroid progenitors confirmed that JMA26 and JMA33 activated HbF synthesis at levels comparable to FK228 with low cellular toxicity. These data support our lead compounds as potential therapeutic agents for further development in the treatment of SCD.en_US
dc.rightsCopyright © 2012 Levi Makala et al.en_US
dc.subjectResearch Articleen_US
dc.titleFK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitorsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3359661en_US
dc.contributor.corporatenameDepartment of Pediatrics-

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