NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform.

Topoisomerase II (Top2) is a ubiquitous nuclear enzyme that relieves torsional stress in chromosomal DNA during various cellular processes. Agents that target Top2, involving etoposide, doxorubicin, and mitoxantrone, are among the most effective anticancer drugs used in the clinic. Mammalian cells possess two genetically distinct Top2 isoforms, both of which are the target of these agents.

OSW-1 analogues: modification of the carbohydrate moiety.

4 OSW-1 analogues featuring modified carbohydrate moieties were prepared. The purpose of these modifications was to assess the importance of certain chemical functions with respect to biological activity. The synthesis and biological activity of the target molecules are shown.

Cytotoxicity of lissoclibadins and lissoclinotoxins, isolated from a tropical ascidian Lissoclinum cf. badium, against human solid-tumor-derived cell lines.

The in vitro growth inhibitory activity of lissoclibadins and lissoclinotoxins isolated from the tropical ascidian Lissoclinum cf. badium against nine human cancer cell lines was examined to evaluate their potential anticancer efficacy. Lissoclibadins 1 (1) and 2 (2), and lissoclinotoxin F (4) showed the strongest activity of the six compounds tested, which were more potent than the anticancer drug cisplatin.

Impact of chymase inhibitor on cardiac function and survival after myocardial infarction.

Objectives: Recent studies have demonstrated that hamsters, like humans, possess both angiotensin converting enzyme (ACE)- and chymase-dependent angiotensin (Ang) II-forming pathways in cardiovascular tissues. We recently found that, after myocardial infarction (MI) in hamsters, cardiac chymase was significantly activated. In order to determine whether suppression of cardiac chymase activity could provide prognostic benefit after MI, we examined the effects of NK3201, a novel, orally active and specific chymase inhibitor, on cardiac function and survival during the acute phase of MI in hamsters.

A novel chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[,4-dioxo-1-phenyl-7-(2-pyridyloxy)]2-heptyl]acetamide (NK3201), suppressed intimal hyperplasia after balloon injury.

In this study, we investigated whether an orally active chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl]acetamide (NK3201), prevents intimal hyperplasia in carotid arteries injured by a balloon catheter in dog. Each dog was administered NK3201 (1 mg/kg per day, p.o.

Development of the chymase inhibitor as an anti-tissue-remodeling drug: myocardial infarction and some other possibilities.

Chymase leading to tissue remodeling is expected to be a potent pharmaceutical target. Its functions in vivo are still unclear, because of lack of orally available inhibitors. Recently, however, the chymase inhibitor NK3201 (2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl] acetamide) was demonstrated to have oral activity against neointimal hyperplasia in dog models (Takai S.