publication . Article . Other literature type . 2019

Atovaquone is active against AML by upregulating the integrated stress pathway and suppressing oxidative phosphorylation

Alexandra M. Stevens; Michael Xiang; Lisa N. Heppler; Isidora Tošić; Kevin Jiang; Jaime O. Munoz; Amos S. Gaikwad; Terzah M. Horton; Xin Long; Padmini Narayanan; ...
Open Access
  • Published: 19 Dec 2019 Journal: Blood Advances, volume 3, pages 4,215-4,227 (issn: 2473-9529, eissn: 2473-9537, Copyright policy)
  • Publisher: American Society of Hematology
Abstract
Atovaquone, a US Food and Drug Administration–approved antiparasitic drug previously shown to reduce interleukin-6/STAT3 signaling in myeloma cells, is well tolerated, and plasma concentrations of 40 to 80 µM have been achieved with pediatric and adult dosing. We conducted preclinical testing of atovaquone with acute myeloid leukemia (AML) cell lines and pediatric patient samples. Atovaquone induced apoptosis with an EC(50) <30 µM for most AML lines and primary pediatric AML specimens. In NSG mice xenografted with luciferase-expressing THP-1 cells and in those receiving a patient-derived xenograft, atovaquone-treated mice demonstrated decreased disease burden an...
Subjects
free text keywords: Atovaquone, medicine.drug, medicine, Pharmacology, business.industry, business, Oxidative phosphorylation, Myeloid Neoplasia
Funded by
EC| iPC
Project
iPC
individualizedPaediatricCure: Cloud-based virtual-patient models for precision paediatric oncology
  • Funder: European Commission (EC)
  • Project Code: 826121
  • Funding stream: H2020 | RIA
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publication . Article . Other literature type . 2019

Atovaquone is active against AML by upregulating the integrated stress pathway and suppressing oxidative phosphorylation

Alexandra M. Stevens; Michael Xiang; Lisa N. Heppler; Isidora Tošić; Kevin Jiang; Jaime O. Munoz; Amos S. Gaikwad; Terzah M. Horton; Xin Long; Padmini Narayanan; ...