Chinese scholar Nature journal reveals new uses of old drugs

        Researchers from the Peking University, the Capital Medical University, and the University of Science and Technology of China confirmed that the alpha 1 receptor blocker, terazosin (terazosin, TZ), activates Pgk1 and Hsp90 to increase resistance to stress. The findings were published in the November 10th Nature Chemical Biology.
        Capital Medical University Liu Lei (Lei Liu) Professor of Peking University, Li Xiaoyu (Xiaoyu Li) Professor, and Wang Jiahuai worked at the University of Science and Technology of China, the Peking University and Harvard Medical School (Jia-huai Wang), this paper co corresponding author.
With the increasing investment in new drug research and development, the increasing risk of listing and the increasing market competition, new drug research and development is facing an increasingly severe test. Especially in the global financial crisis environment, the successful development of a new high yield listed difficulty become more and more important, and the development of new indications for existing drugs, has become an important strategy for drug development.
        Terazosin is a widely marketed selective alpha _1 adrenergic receptor blocker, originally used in the treatment of mild to moderate hypertension. Its pharmacological properties are similar to that of prazosin, but its water solubility is 25 times higher than that of prazosin, and the elimination half-life is 3 times higher than that of prazosin. Therefore, it can be injected intravenously and can only be given 1 times a day. Compared with prazosin, terazosin has the main advantage of obvious antihypertensive effect, long acting time, and favorable effect on blood lipids. In recent years terazosin has also been used in the treatment of bph.
        In this article, the researchers confirmed that terazosin can reduce organ damage and improve survival in rodent models of stroke and sepsis. Through enzyme studies combined with X ray crystallography, they found that terazosin incorporated a new target, Pgk1. And possibly through 2,4-diamino-6,7-dimethoxyisoquinoline, Pgk1 is stimulated to release ATP to activate its enzyme activity. Mechanism studies show that ATP produced by Pgk1 may promote the molecular chaperone activity of a known ATP related enzyme, Pgk1, Hsp90. When the Hsp90 is activated, it increases the resistance to a variety of stresses.
        The new study confirms that terazosin has a new protein target, Pgk1, and reveals its molecular effects. As a clinical drug, it may be possible to rapidly turn terazosin into an organ damaging disease such as stroke and sepsis.