Delving into the Latest Updates on WX-293 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

uPA

Mechanism

uPA inhibitors(Urokinase plasminogen activator inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Wilex GmbH Im- u. Export von Investitions- und Verbrauchsgüter

Active Organization-

Inactive Organization

Wilex GmbH Im- u. Export von Investitions- und Verbrauchsgüter

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

One of the key consequences of cutaneous wounding is the development of tissue hypoxia. Recent data have suggested that this is a potent stimulus for increased keratinocyte migration and hence re-epithelialization, although the mechanisms responsible for this remain unclear. In this study we have investigated the relationship between hypoxia, plasminogen activation, and in vitro wound healing. Exposure of keratinocyte cultures to hypoxia resulted in upregulation of urokinase plasminogen activator mRNA and a subsequent increase in urokinase plasminogen activator-mediated plasminogen activation, as determined by indirect chromogenic peptide assay and plasminogen-linked zymography. Analysis of keratinocyte wound healing in vitro confirmed enhanced wound closure in hypoxic cultures compared with normoxic cultures after 16 h. Pretreatment of normoxic and hypoxic cultures with mitomycin C and cytochalasin B indicated that in this system wound closure was due to keratinocyte migration rather than proliferation. Addition of the broad-spectrum serine proteinase inhibitor, p-aminobenzamidine, or the specific urokinase plasminogen activator inhibitors, amiloride and WX-293, significantly reduced wound closure in hypoxic cultures and abrogated the hypoxic enhancement of wound closure. These data indicate a central role for urokinase plasminogen activators in hypoxic keratinocyte migration and suggest a potential mechanism for enhanced re-epithelialization of wounds under low oxygen tensions.

100 Deals associated with WX-293

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