Parkhitko, Andrey A.;Priolo, Carmen;Coloff, Jonathan L.;Yun, Jihye;Wu, Julia J.;Mizumura, Kenji;Xu, Wenping;Malinowska, Izabela A.;Yu, Jane;Kwiatkowski, David J.;Locasale, Jason W.;Asara, John M.;Choi, Augustine M. K.;Finkel, Toren;Henske, Elizabeth P. published 《Autophagy-Dependent Metabolic Reprogramming Sensitizes TSC2-Deficient Cells to the Antimetabolite 6-Aminonicotinamide》. The research results were published in《Molecular Cancer Research》 in 2014.COA of Formula: C6H7N3O The article conveys some information:
The mammalian target of rapamycin complex 1 (mTORC1) is hyperactive in many human cancers and in tuberous sclerosis complex (TSC). Autophagy, a key mTORC1-targeted process, is a critical determinant of metabolic homeostasis. Metabolomic profiling was performed to elucidate the cellular consequences of autophagy dysregulation under conditions of hyperactive mTORC1. It was discovered that TSC2-null cells have distinctive autophagy-dependent pentose phosphate pathway (PPP) alterations. This was accompanied by enhanced glucose uptake and utilization, decreased mitochondrial oxygen consumption, and increased mitochondrial reactive oxygen species (ROS) production Importantly, these findings revealed that the PPP is a key autophagy-dependent compensatory metabolic mechanism. Furthermore, PPP inhibition with 6-aminonicotinamide (6-AN) in combination with autophagy inhibition suppressed proliferation and prompted the activation of NF-κB and CASP1 in TSC2-deficient, but not TSC2-proficient cells. These data demonstrate that TSC2-deficient cells can be therapeutically targeted, without mTORC1 inhibitors, by focusing on their metabolic vulnerabilities. Implications: This study provides proof-of-concept that therapeutic targeting of diseases with hyperactive mTORC1 can be achieved without the application of mTORC1 inhibitors. Mol Cancer Res; 12(1); 48-57. ©2013 AACR. The experimental procedure involved many compounds, such as 6-Aminonicotinamide (cas: 329-89-5) .
6-Aminonicotinamide (cas:329-89-5)COA of Formula: C6H7N3O is a well-established inhibitor of the NADP+-dependent enzyme, 6-phosphogluconate dehydrogenase (Ki = 0.46 μM). 6-Aminonicotinamide also reduces cardiovascular oxidative injury following ischemia/reperfusion.
Reference:
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Amide – an overview | ScienceDirect Topics