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Tumour hypoxia is a well-known hallmark of malignant tumours and is associated with a poor outcome. Hypoxia induces the production of hypoxia-inducible factors (HIF) that activate various oncogenic processes. Under aerobic conditions, alpha-ketoacids (KAs) act as essential cofactors of key enzymes involved in fatty acid metabolism. However, their production is drastically increased in hypoxic cells as a result of decreased conversion to alpha-hydroxyacids mediated by the activity of hypoxia-inducible enzymes. We sought to characterize the pharmacokinetic properties of a novel, highly selective α-Ketoacid Reductase (KAR) inhibitor, NS309. In this study, we performed a phase I/II dose escalation study, assessing intravenous (i.v.) administration of NS309 in a cohort of children with refractory solid tumours. We observed a single agent exposure that correlated with the volume of distribution, clearance, and half-life of NS309. We also observed a significant accumulation of NS309 in tumours, despite its rapid systemic elimination. We showed that

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TRT () is a South Korean hip-hop duo, formed by hip-hop musicians Lao and BZY (both members of former hip-hop duo Troublemakers, which split up in 2005). The duo consists of Lao and BZY’s hip-hop group, F1rst, formed in 2006, and thus their hip-hop label, F1rst World.

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