A-350619 hydrochloride

Guanylyl cyclases are signal transduction enzyme that convert GTP to cyclic GMP. Soluble guanylate cyclase is activated by a gaseous ligand, nitric oxide.. The nitric oxide activation of soluble guanylate, resulting in GTP conversion to GMP, is important in physiological processes such as as smooth muscle relaxation, neurotransmission, inhibition of platelet aggregation and immune response. A-350619 is an activator of soluble guanylyl cyclase.

A-350619 relaxes cavernosum tissue strips in a dose dependent manner with EC₅₀ of 80 μMM. Because A-350619 at 1 μMmol/kg induces penile erection in a conscious rat model, it may be useful as an alternate method of enhancing the effect of nitric oxide for the treatment of sexual dysfunction.

A-350619 modulates catalytic properties of soluble guanylyl cyclase; it increases V_mas from 0.1 to 14.5 μmol/min/mg and lowers K_m from 300 to 50 μM. A-350619 activation of soluble guanylate cyclase depends on the presence of a heme moiety in the enzyme and synergy with nitric oxide.

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