Non-peptidic urotensin-II receptor modulators

ISSN： 1354-3776

Source： Expert Opinion on Therapeutic Patents, Vol.16, Iss.4, 2006-04, pp. : 467-479

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Abstract

Urotensin-II (U-II), first isolated as a fish neuropeptide, is the most potent vasoconstrictor known to date. Through the interaction with its cognate 7-transmembrane receptor UT (formerly known as the orphan receptor GPR14), U-II has demonstrated potent vasoconstrictor activity in mammalian tissues including those from rats, monkeys and, most importantly, humans. Systemic administration of human U-II (hU-II) in monkey, cat and human induced profound cardiohaemodynamic effects. The U-II/UT system is purported to be involved in the (dys)regulation of cardiorenal and metabolic function and hU-II has been implicated in the aetiology of numerous diseases including hypertension, heart failure, atherosclerosis, renal failure, cirrhosis and diabetes. The impressive in vitro and in vivo pharmacological activity of U-II has stimulated a great deal of interest in identifying, designing and developing non-peptidic small molecule UT modulators. Significant advances have been made in this young but rapidly emerging research field with several classes of potent, selective and bioavailable UT antagonists being recently discovered and disclosed. This review will highlight the advances that have been made in the non-peptidic small molecule UT modulator area.