Pharmacopeia's PS433540 enters Ph I trial

US small-molecule drugmaker Pharmacopeia reported positive results from a Phase I trial of PS433540, its lead internal product candidate for the treatment of hypertension and diabetic nephropathy. Data from the single ascending-dose study indicated that PS433540 was well-tolerated at all six doses administered, the firm noted, adding that the study findings suggested that it possesses linear pharmacokinetics and a half-life that is consistent with once-daily administration.

The drug is the first and only dual-acting angiotensin and endothelin receptor antagonist (DARA) in development. The compound, which has two clinically-validated mechanisms of action in a single molecule, works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II and endothelin 1, at their respective receptors. PS433540 is highly selective (10,000-fold) for the AII receptor sub-type 1 and the ET receptor sub-type A. As such, PS433540 combines the properties of an angiotensin receptor blocker and an endothelin receptor antagonist in the same molecule.