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Topical Nitric oxide-releasing PDE5 inhibitor for wound healing indications.
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<blockquote data-quote="madman" data-source="post: 189966" data-attributes="member: 13851"><p><strong>TOP-N53: <span style="color: rgb(184, 49, 47)">A Clinical Drug Candidate for the Treatment of Non-healing Wounds </span></strong></p><p></p><p><span style="color: rgb(44, 130, 201)">Reto Naef, Hermann Tenor, and Guido Koch </span></p><p></p><p></p><p></p><p></p><p></p><p><strong>Abstract:</strong><em><span style="color: rgb(184, 49, 47)"> Chronic non-healing wounds impose a huge burden on patients and health care providers. In spite of improvements in standards of care, there are no effective and safe treatments that promote new tissue formation and wound closure in ailments such as diabetic foot ulcer, pressure ulcer, venous leg ulcer, or digital ulcer in systemic sclerosis. </span></em><span style="color: rgb(44, 130, 201)"><em>Endothelial dysfunction, which associates with impaired endogenous nitric oxide formation is assumed to be the main disease mechanism in chronic, non-healing wounds in diabetic and elderly patients as well as in digital ulcers in systemic sclerosis. </em></span><span style="color: rgb(184, 49, 47)"><em><u>Topadur Pharma has invented small molecular weight nitric oxide-releasing PDE5 inhibitors, which by modulating a key enzyme system of intracellular signaling may address chronic non-healing wounds</u>. The promising first drug candidate TOP-N53 is currently in early clinical development. Here we describe for the first time the design of TOP-N53 and the synthesis of the clinical GMP batch. </em></span></p><p></p><p></p><p></p><p></p><p><strong>1. Chronic Non-healing Wounds with a High Medical Need</strong></p><p></p><p><span style="color: rgb(184, 49, 47)"><em>TOPADUR Pharma AG owns an R&D platform targeting several aging-related diseases, including new therapies for wound healing indications.</em></span> <span style="color: rgb(44, 130, 201)"><em>In spite of the current standard of care, there remains a high medical need for effective drug treatment of chronic wounds such as diabetic foot ulcer, pressure ulcer, digital ulcers in systemic sclerosis, venous leg ulcers, dental wounds, or scars from surgery performed on elderly patients, where wound healing is delayed or fails.</em></span></p><p></p><p></p><p></p><p></p><p><strong>2. Design of Dual Function NO-releasing PDE5 Inhibitors </strong></p><p></p><p><em><span style="color: rgb(184, 49, 47)">When Topadur Pharma AG was founded in 2015, sGC and PDE5 were validated targets and several drugs were on the market and in development based on the NO/sGC/cGMP signaling cascade.</span></em><span style="color: rgb(44, 130, 201)"> <u>cGMP elevating drugs impart vasodilatation but antifibrotic, anti-inflammatory, anti-proliferative, and anti-cancer effects have been described as well</u>.[14] </span></p><p></p><p></p><p></p><p></p><p><strong>3. Product/Service and Outlook </strong></p><p></p><p><em><span style="color: rgb(184, 49, 47)"><strong>The medicinal chemistry project resulted in a remarkably potent and efficacious drug candidate which translated well into efficacy in preclinical wound healing models.[18]</strong></span></em><strong> <span style="color: rgb(44, 130, 201)"><em>TOP-N53 is currently embarking on clinical development as a topical treatment for wound healing indications. </em></span></strong></p></blockquote><p></p>
[QUOTE="madman, post: 189966, member: 13851"] [B]TOP-N53: [COLOR=rgb(184, 49, 47)]A Clinical Drug Candidate for the Treatment of Non-healing Wounds [/COLOR][/B] [COLOR=rgb(44, 130, 201)]Reto Naef, Hermann Tenor, and Guido Koch [/COLOR] [B]Abstract:[/B][I][COLOR=rgb(184, 49, 47)] Chronic non-healing wounds impose a huge burden on patients and health care providers. In spite of improvements in standards of care, there are no effective and safe treatments that promote new tissue formation and wound closure in ailments such as diabetic foot ulcer, pressure ulcer, venous leg ulcer, or digital ulcer in systemic sclerosis. [/COLOR][/I][COLOR=rgb(44, 130, 201)][I]Endothelial dysfunction, which associates with impaired endogenous nitric oxide formation is assumed to be the main disease mechanism in chronic, non-healing wounds in diabetic and elderly patients as well as in digital ulcers in systemic sclerosis. [/I][/COLOR][COLOR=rgb(184, 49, 47)][I][U]Topadur Pharma has invented small molecular weight nitric oxide-releasing PDE5 inhibitors, which by modulating a key enzyme system of intracellular signaling may address chronic non-healing wounds[/U]. The promising first drug candidate TOP-N53 is currently in early clinical development. Here we describe for the first time the design of TOP-N53 and the synthesis of the clinical GMP batch. [/I][/COLOR] [B]1. Chronic Non-healing Wounds with a High Medical Need[/B] [COLOR=rgb(184, 49, 47)][I]TOPADUR Pharma AG owns an R&D platform targeting several aging-related diseases, including new therapies for wound healing indications.[/I][/COLOR] [COLOR=rgb(44, 130, 201)][I]In spite of the current standard of care, there remains a high medical need for effective drug treatment of chronic wounds such as diabetic foot ulcer, pressure ulcer, digital ulcers in systemic sclerosis, venous leg ulcers, dental wounds, or scars from surgery performed on elderly patients, where wound healing is delayed or fails.[/I][/COLOR] [B]2. Design of Dual Function NO-releasing PDE5 Inhibitors [/B] [I][COLOR=rgb(184, 49, 47)]When Topadur Pharma AG was founded in 2015, sGC and PDE5 were validated targets and several drugs were on the market and in development based on the NO/sGC/cGMP signaling cascade.[/COLOR][/I][COLOR=rgb(44, 130, 201)] [U]cGMP elevating drugs impart vasodilatation but antifibrotic, anti-inflammatory, anti-proliferative, and anti-cancer effects have been described as well[/U].[14] [/COLOR] [B]3. Product/Service and Outlook [/B] [I][COLOR=rgb(184, 49, 47)][B]The medicinal chemistry project resulted in a remarkably potent and efficacious drug candidate which translated well into efficacy in preclinical wound healing models.[18][/B][/COLOR][/I][B] [COLOR=rgb(44, 130, 201)][I]TOP-N53 is currently embarking on clinical development as a topical treatment for wound healing indications. [/I][/COLOR][/B] [/QUOTE]
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Topical Nitric oxide-releasing PDE5 inhibitor for wound healing indications.
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