Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients...

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Veröffentlicht in:	Nature medicine 2023, Vol.29 (1), p.115-126
Hauptverfasser:	Yap, Timothy A., Daver, Naval, Mahendra, Mikhila, Zhang, Jixiang, Kamiya-Matsuoka, Carlos, Meric-Bernstam, Funda, Kantarjian, Hagop M., Ravandi, Farhad, Collins, Meghan E., Francesco, Maria Emilia Di, Dumbrava, Ecaterina E., Fu, Siqing, Gao, Sisi, Gay, Jason P., Gera, Sonal, Han, Jing, Hong, David S., Jabbour, Elias J., Ju, Zhenlin, Karp, Daniel D., Lodi, Alessia, Molina, Jennifer R., Baran, Natalia, Naing, Aung, Ohanian, Maro, Pant, Shubham, Pemmaraju, Naveen, Bose, Prithviraj, Piha-Paul, Sarina A., Rodon, Jordi, Salguero, Carolina, Sasaki, Koji, Singh, Anand K., Subbiah, Vivek, Tsimberidou, Apostolia M., Xu, Quanyun A., Yilmaz, Musa, Zhang, Qi, Li, Yuan, Bristow, Christopher A., Bhattacharjee, Meenakshi B., Tiziani, Stefano, Heffernan, Timothy P., Vellano, Christopher P., Jones, Philip, Heijnen, Cobi J., Kavelaars, Annemieke, Marszalek, Joseph R., Konopleva, Marina
Format:	Artikel
Sprache:	eng
Schlagworte:	631/154/1438 631/154/570 631/67 631/67/1059/153 631/67/2327 Acute myeloid leukemia Animals Anticancer properties Antineoplastic Agents - adverse effects Antitumor activity Antitumor agents Biomedical and Life Sciences Biomedicine Cancer Research Clinical trials Constraining Electron transport chain Histone deacetylase Histone Deacetylase Inhibitors - therapeutic use Humans Infectious Diseases Inhibitors Kinases Lactic acid Leukemia Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - pathology Metabolic Diseases Mice Mitochondria Molecular Medicine NADH-ubiquinone oxidoreductase Neoplasms - pathology Neurosciences Neurotoxicity Oxidative Phosphorylation Peripheral neuropathy Phosphorylation Solid tumors
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