Gliocidin is a nicotinamide-mimetic prodrug that targets glioblastoma – Nature
Xie, X. P. et al. Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy. Dev. Cell 57, 32–46 (2022).
Google Scholar
Valvezan, A. J. et al. IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex. JCI Insight 5, e135071 (2020).
Google Scholar
Johnson, M. C. & Kollman, J. M. Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation. eLife 9, e53243 (2020).
Google Scholar
Lim, M. et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 24, 1935–1949 (2022).
Google Scholar
Reardon, D. A. et al. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: the CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol. 6, 1003–1010 (2020).
Google Scholar
Shi, Y. et al. Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma. Nature 567, 341–346 (2019).
Google Scholar
Kwon, C. H. et al. Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res. 68, 3286–3294 (2008).
Google Scholar
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR–Cas9. Nat. Biotechnol. 34, 184–191 (2016).
Google Scholar
Saxton, R. A. & Sabatini, D. M. mTOR signaling in growth, metabolism, and disease. Cell 168, 960–976 (2017).
Google Scholar
Valvezan, A. J. et al. mTORC1 couples nucleotide synthesis to nucleotide demand resulting in a targetable metabolic vulnerability. Cancer Cell 32, 624–638 (2017).
Google Scholar
Bester, A. C. et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145, 435–446 (2011).
Google Scholar
Bieganowski, P. & Brenner, C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss–Handler independent route to NAD+ in fungi and humans. Cell 117, 495–502 (2004).
Google Scholar
Cooney, D. A. et al. Studies on the mechanism of action of tiazofurin metabolism to an analog of NAD with potent IMP dehydrogenase-inhibitory activity. Adv. Enzyme Regul. 21, 271–303 (1983).
Google Scholar
Monecke, T. et al. Crystal structures of the novel cytosolic 5′-nucleotidase IIIB explain its preference for m7GMP. PLoS ONE 9, e90915 (2014).
Google Scholar
Pastor-Anglada, M. & Perez-Torras, S. Emerging roles of nucleoside transporters. Front. Pharmacol. 9, 606 (2018).
Google Scholar
Hedstrom, L. IMP dehydrogenase: structure, mechanism, and inhibition. Chem. Rev. 109, 2903–2928 (2009).
Google Scholar
Sintchak, M. D. et al. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 85, 921–930 (1996).
Google Scholar
Chau, V. et al. Preclinical therapeutic efficacy of a novel pharmacologic inducer of apoptosis in malignant peripheral nerve sheath tumors. Cancer Res. 74, 586–597 (2014).
Google Scholar
Song, T. et al. The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription. J. Biol. Chem. 288, 20908–20917 (2013).
Google Scholar
Shireman, J. M. et al. De novo purine biosynthesis is a major driver of chemoresistance in glioblastoma. Brain 144, 1230–1246 (2021).
Google Scholar
Kofuji, S. et al. IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma. Nat. Cell Biol. 21, 1003–1014 (2019).
Google Scholar
Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083–1086 (2017).
Google Scholar
Alquicira-Hernandez, J. & Powell, J. E. Nebulosa recovers single-cell gene expression signals by kernel density estimation. Bioinformatics 37, 2485–2487 (2021).
Google Scholar
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
Google Scholar
Chambers, M. C. et al. A cross-platform toolkit for mass spectrometry and proteomics. Nat. Biotechnol. 30, 918–920 (2012).
Google Scholar
Pluskal, T. et al. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics 11, 395 (2010).
Google Scholar
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
Google Scholar
Punjani, A. et al. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Google Scholar
Bepler, T. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153–1160 (2019).
Google Scholar
Terwilliger, T. C. et al. Improvement of cryo-EM maps by density modification. Nat. Methods 17, 923–927 (2020).
Google Scholar
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Google Scholar
Moriarty, N. W., Grosse-Kunstleve, R. W. & Adams, P. D. electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr. D Biol. Crystallogr. 65, 1074–1080 (2009).
Google Scholar
Emsley, P. et al. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).
Google Scholar
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531–544 (2018).
Google Scholar
Davis, I. W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375–W383 (2007).
Google Scholar
Zhang, J. et al. Design, synthesis, and evaluation of inhibitors for severe acute respiratory syndrome 3C-like protease based on phthalhydrazide ketones or heteroaromatic esters. J. Med. Chem. 50, 1850–1864 (2007).
Google Scholar
Bollenbach, M. et al. Efficient and mild Ullmann-type N-arylation of amides, carbamates, and azoles in water. Chemistry 23, 13676–13683 (2017).
Google Scholar
Ikawa, T. et al. Pd-catalyzed amidation of aryl chlorides using monodentate biaryl phosphine ligands: a kinetic, computational, and synthetic investigation. J. Am. Chem. Soc. 129, 13001–13007 (2007).
Google Scholar
Ganbold, M. Gliocidin. Zenodo https://doi.org/10.5281/zenodo.13845197 (2024).
