Lin, Yu-HsiSatani, NikunjHammoudi, NaimaYan, Victoria C.Barekatain, YasamanKhadka, SunadaAckroyd, Jeffrey J.Georgiou, Dimitra K.Pham, Cong-DatArthur, KenishaMaxwell, DavidPeng, ZhenghongLeonard, Paul G.Czako, BarbaraPisaneschi, FedericaMandal, PijusSun, YutingZielinski, RafalPando, Susana CastroWang, XiaoboTran, TheresaXu, QuanyuWu, QiJiang, YongyingKang, ZhijunAsara, JohnPriebe, WaldemarBornmann, WilliamMarszalek, Joseph R.DePinho, Ronald A.Muller, Florian L.2022-03-042020-11-23Lin, Yu-Hsi, Nikunj Satani, Naima Hammoudi, Victoria C. Yan, Yasaman Barekatain, Sunada Khadka, Jeffrey J. Ackroyd et al. "An enolase inhibitor for the targeted treatment of ENO1-deleted cancers." Nature Metabolism 2, no. 12 (2020): 1413-1426. DOI: 10.1038/s42255-020-00313-32522-5812https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370942Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We previously identified a subset of cancers harboring homozygous deletion of the glycolytic enzyme Enolase (ENO1) with exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small molecule Enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumors in mice at doses well-tolerated in non-human primates. Our data provide in vivo proof-of-principal for the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential across a range of therapeutic settings.en-USCell BiologyPhysiology (medical)Endocrinology, Diabetes and MetabolismInternal MedicineJournal Article2022-03-0410.1038/s42255-020-00313-3