Sica et al. show that respiratory chain inhibition by 1-cyclopropyl-4-(4-[(5-methyl-3-(3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl]pyridin-2-yl)piperazine (BAY87-2243, abbreviated as B87) becomes lethal for cancer cells when glycolysis is simultaneously suppressed. When combined with B87, dimethyl α-ketoglutarate acquires the capacity to suppress glycolysis, thus lethally poisoning bioenergetics metabolism. This therapeutic combination effect relies on transcriptional reprogramming that can be reverted by pharmacological inhibition of MDM2.
Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate / Sica, V.; Bravo-San Pedro, J. M.; Izzo, V.; Pol, J.; Pierredon, S.; Enot, D.; Durand, S.; Bossut, N.; Chery, A.; Souquere, S.; Pierron, G.; Vartholomaiou, E.; Zamzami, N.; Soussi, T.; Sauvat, A.; Mondragon, L.; Kepp, O.; Galluzzi, L.; Martinou, J. -C.; Hess-Stumpp, H.; Ziegelbauer, K.; Kroemer, G.; Maiuri, M. C.. - In: CELL REPORTS. - ISSN 2211-1247. - 27:3(2019), pp. 820-834.e9. [10.1016/j.celrep.2019.03.058]
Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate
Maiuri M. C.
Ultimo
2019
Abstract
Sica et al. show that respiratory chain inhibition by 1-cyclopropyl-4-(4-[(5-methyl-3-(3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl]pyridin-2-yl)piperazine (BAY87-2243, abbreviated as B87) becomes lethal for cancer cells when glycolysis is simultaneously suppressed. When combined with B87, dimethyl α-ketoglutarate acquires the capacity to suppress glycolysis, thus lethally poisoning bioenergetics metabolism. This therapeutic combination effect relies on transcriptional reprogramming that can be reverted by pharmacological inhibition of MDM2.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
