Document Detail

Anti-proliferative and anti-leukemic activity of DDE46 (compound WHI-07), a novel bromomethoxylated arylphosphate derivative of zidovudine, and related compounds. Studies using human acute lymphoblastic leukemia cells and the zebrafish model.
MedLine Citation:
PMID:  15787279     Owner:  NLM     Status:  MEDLINE    
The anti-proliferative effects of a novel bromomethoxylated arylphosphate derivative of zidovudine (compound DDE46, CAS 213982-96-8) were first examined in a zebra fish embryo model. DDE46 blocked the cell division at the 2-cell stage of the embryonic development followed by total cell fusion. DDE46 also inhibited the proliferation of the leukemic cell lines NALM-6 and MOLT-3. DDE46 enhanced the activity of the pro-apoptotic enzymes Caspase-3, Caspase-6, Caspase-8, and Caspase-9 leading to the apoptotic death of the leukemic cell line Jurkat. These results justify the further development of this agent as a new anti-leukemic drug candidate.
Alexey O Benyumov; Taracad K Venkatachalam; Olga O Grigoriants; Alexei O Vassilev; Heather E Tibbles; Suzanne Downs; Darin Dumezb; Fatih M Uckun
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  55     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  2005  
Date Detail:
Created Date:  2005-03-24     Completed Date:  2005-04-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  114-22     Citation Subset:  IM    
Departments of Embryology, Parker Hughes Institute, Roseville, MN 55113, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*,  therapeutic use
Apoptosis / drug effects
Caspases / antagonists & inhibitors
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Jurkat Cells
Leukemia / drug therapy*
Magnetic Resonance Spectroscopy
Nephelometry and Turbidimetry
Prodrugs / pharmacology
Tetrazolium Salts
Thymidine Monophosphate / analogs & derivatives*,  pharmacology*
Tubulin / biosynthesis,  genetics
Zidovudine / analogs & derivatives*,  pharmacology*
Reg. No./Substance:
0/5-bromo-6-methoxy-5, 6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate; 0/Antineoplastic Agents; 0/Dideoxynucleotides; 0/Prodrugs; 0/Tetrazolium Salts; 0/Thiazoles; 0/Tubulin; 298-93-1/thiazolyl blue; 30516-87-1/Zidovudine; 365-07-1/Thymidine Monophosphate; EC 3.4.22.-/Caspases

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