4.7 Article

Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells

Journal

JOURNAL OF MEDICINAL CHEMISTRY
Volume 66, Issue 17, Pages 12101-12114

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.3c00676

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This research aims to design and develop tumor-homing peptide complexes of arsenic to strategically target specific cancers, with the goal of achieving dose reduction and decreased side effects. Studies show that the most stable complex exhibits 1000 times greater toxicity towards leukemia cells than human blood cells, indicating potential for in vivo studies.
Arsenic, in the simple form of arsenic trioxide, is currentlymarketedfor the treatment of acute promyelocytic leukemia. Due to the multifacetedmechanisms of action of arsenic, it has also shown promise in othertypes of leukemias but is hindered by its toxic effects toward normalcells. This research has aimed to determine whether tumor-homing peptidecomplexes of arsenic can be designed and developed to strategicallytarget specific cancers. The end goal is to achieve dose reductionand decreased side effects of the resultant arsenic therapeutic agent.In this article, we present the synthesis, characterization, and stabilitystudies of a new class of As-peptide complexes designed to targetleukemia. In vitro biological studies of the moststable complex show 1000 times greater toxicity toward leukemia cellsover human blood cells, indicating potential for progression to in vivo studies.

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