Publication Date:
2014-12-06
Description:
Recent studies indicate that acute myeloid leukemia (AML) cells, including leukemia-initiating cells, are highly dependent on oxidative phosphorylation (OXPHOS) for survival, while normal hematopoietic stem cells predominantly utilize glycolysis for energy homeostasis. We have reported development of a series of novel, highly potent mitochondrial complex I inhibitors, which in vitro inhibit complex I with IC50 values 20% or for signs of morbidity. Right, bioluminescence imaging before (D0) and 10 days after 1 st dose; left survival. Figure 1. Treatment with IACS-1131 prolongs survival in a OCI-AML3 xenograft model. Luciferase-expressing OCI-AML3 cells were injected in the tail vein of NSG mice. On day 16 after injection, engraftment was confirmed and mice were randomized on the basis of IVIS-based imaging of luciferase activity after luciferin injection. For the next 58 days, mice received either vehicle or 60 mg/kg/day of IACS-1131 via oral gavage. Mice were sacrificed when body weight was reduced by 〉20% or for signs of morbidity. Right, bioluminescence imaging before (D0) and 10 days after 1 st dose; left survival. Disclosures No relevant conflicts of interest to declare.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine