ArticleNature medicine2018
An inhibitor of oxidative phosphorylation exploits cancer vulnerability.
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Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 627 papers.
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627citing papers in PubMed
32.3field-weighted citation impact, top 1% of its field
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Who cites it
627 citing papers in PubMed, 924 citations in OpenAlex.
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- Mitochondrial DNA mutations are associated with impaired oxidative phosphorylation and enhanced imatinib response in chronic myeloid leukemia.HemaSphere · 2026Article
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- Mitochondrial Fitness as a Functional Immune Checkpoint in Cancer: Metabolic Plasticity, Tumor Evolution, and Immunotherapy.Cancers · 2026Review
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- SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs.British journal of cancer · 2026Article
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- LyP vs advanced-stage CTCLs: single-cell profiling reveals markers of self-limited vs aggressive disease behavior.Blood advances · 2026Article
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- Tumoral Metabolism at the Intersection of Oncogene Signaling, Epigenetics and Immunology: Emerging Therapeutic Strategies in Cancer.Current issues in molecular biology · 2026Review
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- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.Science advances · 2026Article
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
567 more citing papers are in PubMed but not listed here.
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Authors and funding
66 authors at 4 institutions in 4 countries.
Jennifer R MolinaInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuting SunInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Marina ProtopopovaInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sonal GeraInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Madhavi BandiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Christopher BristowInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Timothy McAfoosInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pietro MorlacchiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jeffrey AckroydDepartment of Cancer Imaging Systems, University of Texas MD Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-3796-4447
Ahmed-Noor A AgipMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, UK.
Gheath Al-AtrashDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John AsaraBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jennifer BardenhagenInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Caroline C CarrilloDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Christopher CarrollInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Edward ChangInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stefan CiureaDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jason B CrossInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Barbara CzakoInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Angela DeemInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Naval DaverDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John Frederick de GrootDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jian-Wen DongDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ningping FengInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guang GaoInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jason GayInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mary Geck DoInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jennifer GreerInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Virginia GiulianiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jing HanInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lina HanDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Verlene K HenryDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Judy HirstMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, UK.
Sha HuangInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yongying JiangInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhijun KangInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tin KhorInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sergej KonoplevDepartment of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yu-Hsi LinDepartment of Cancer Imaging Systems, University of Texas MD Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5763-1530
Gang LiuInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alessia LodiDepartment of Nutritional Sciences, University of Texas at Austin, Austin, TX, USA.
Timothy LoftonInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Helen MaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mikhila MahendraInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Polina MatreDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Robert MullinaxInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael PeoplesInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alessia PetrocchiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jaime Rodriguez-CanaleDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Riccardo SerreliMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, UK.
Thomas ShiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Melinda SmithInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yoko TabeDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jay TheroffInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stefano TizianiDepartment of Nutritional Sciences, University of Texas at Austin, Austin, TX, USA.
Quanyun XuInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Qi ZhangDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Florian MullerDepartment of Cancer Imaging Systems, University of Texas MD Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7568-2948
Ronald A DePinhoDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Carlo ToniattiInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Giulio F DraettaInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5225-9610
Timothy P HeffernanInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Marina KonoplevaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Philip JonesInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M Emilia Di FrancescoInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph R MarszalekInstitute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA. jrmarszalek@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USUniversity of Cambridge · GBThe University of Texas at Austin · USBeth Israel Deaconess Medical Center · US
Funding
Medical Research Council MC_U105663141Medical Research Council MC_UP_1002/1Medical Research Council MC_UU_00015/2Medical Research Council MC_UU_00015/7
Abstract
Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors.
Indexed as
Oxidative PhosphorylationAnimalsBiomarkers, TumorCell Line, TumorEnergy MetabolismGlycolysisHEK293 CellsHumansLactic AcidLeukemia, Myeloid, AcuteMiceMitochondriaNeoplasmsNucleotidesTumor BurdenXenograft Model Antitumor AssaysBiomarkers, TumorLactic AcidNucleotides
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