Liew, Lydia P. published the artcileHypoxia-Activated Prodrugs of PERK Inhibitors, Formula: C9H10O3, the main research area is hypoxia prodrug drug delivery PERK kinase inhibitor antitumor; drug delivery; hypoxia; kinase inhibitor; nitroimidazole; prodrug.
Tumor hypoxia plays an important role in tumor progression and resistance to therapy. Under hypoxia unfolded proteins accumulate in the endoplasmic reticulum (ER) and this stress is relieved through the protein kinase R-like ER kinase (PERK) signaling arm of the unfolded protein response (UPR). Targeting the UPR through PERK kinase inhibitors provides tumor growth inhibition, but also elicits on-mechanism normal tissue toxicity. Hypoxia presents a target for tumor-selective drug delivery using hypoxia-activated prodrugs. We designed and prepared hypoxia-activated prodrugs of modified PERK inhibitors using a 2-nitroimidazole bioreductive trigger. The new inhibitors retained PERK kinase inhibitory activity and the corresponding prodrugs were strongly deactivated. The prodrugs were able to undergo fragmentation following radiolytic reduction, or bioreduction in HCT116 cells, to release their effectors, albeit inefficiently. We examined the effects of the prodrugs on PERK signaling in hypoxic HCT116 cells. This study has identified a 2-substituted nitroimidazole carbamate prodrug with potential to deliver PERK inhibitors in a hypoxia-selective manner.
Chemistry – An Asian Journal published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Formula: C9H10O3.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem