Animal experiment:

Pigs: Two female pigs are subjected to eight excisional wounds. The wounds are dressed and treated daily for 10 days with either 1 mL of a 10 mg/mL formulation of UK-371804 in hydrogel vehicle, or hydrogel vehicle alone (control). On day 11 the animals are sacrificed, terminal blood samples are taken to assess any systemic exposure of the compounds, and the wounds are excised from the surrounding normal skin[1].

UK-371804 is a urokinase-type plasminogen activator (uPA) inhibitor with a Ki of 10 nM.

UK-371804 is able to inhibit exogenous uPA in human chronic wound fluid (IC50=0.89 μM). UK-371804 has its excellent enzyme potency (Ki=10 nM) and selectivity profile (4000-fold versus tPA and 2700-fold versus plasmin)[1].

In a porcine acute excisional wound model, following topical delivery, UK-371804 is able to penetrate into pig wounds and inhibit exogenous uPA activity with no adverse effect on wound healing parameters. Concentrations of UK-371804 in the dermis are 41.8 μM[1].

[1]. Fish PV, et al. Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51.