FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors
Author
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-14
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Makala, Levi. 2012. FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors. Anemia،Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-471444
Modern Language Association (MLA)
Makala, Levi. FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors. Anemia No. 2012 (2012), pp.1-13.
https://search.emarefa.net/detail/BIM-471444
American Medical Association (AMA)
Makala, Levi. FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors. Anemia. 2012. Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-471444
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-471444