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TOP-N53: A Clinical Drug Candidate for the Treatment of Non-healing Wounds
Reto Naef1, Hermann Tenor2, Guido Koch2
1Topadur Pharma AG, Grabenstrasse 11A, CH-8952 Schlieren, Switzerland;,
Abstract:
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. Endothelial dysfunction, which associates with impaired endogenous nitric oxide formation is assumed to be a main disease mechanism in chronic, non-healing wounds in diabetic and elderly patients as well as in digital ulcers in systemic sclerosis. 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. 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.
Insights
New nitric oxide-releasing PDE5 inhibitors show promise for treating chronic non-healing wounds, such as diabetic foot ulcers. The drug candidate TOP-N53 is in early clinical development for improved wound healing.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Wound Healing Research
Background:
- Chronic non-healing wounds, including diabetic foot ulcers and venous leg ulcers, present significant clinical challenges.
- Endothelial dysfunction and impaired nitric oxide (NO) formation are implicated as key mechanisms in these persistent wounds.
- Current treatments offer limited efficacy in promoting tissue regeneration and wound closure.
Purpose of the Study:
- To introduce a novel class of small molecule, nitric oxide-releasing phosphodiesterase type 5 (PDE5) inhibitors.
- To describe the design and synthesis of TOP-N53, a promising drug candidate for chronic wound treatment.
- To explore the potential of modulating intracellular signaling pathways for enhanced wound healing.
Main Methods:
- Design and synthesis of nitric oxide-releasing PDE5 inhibitors.
- Characterization of the drug candidate TOP-N53.
- Synthesis of a clinical Good Manufacturing Practice (GMP) batch of TOP-N53.
Main Results:
- Successful design and synthesis of TOP-N53, a novel NO-releasing PDE5 inhibitor.
- Production of a clinical GMP-grade batch of TOP-N53.
- TOP-N53 is positioned for early clinical development to address unmet needs in wound care.
Conclusions:
- Novel NO-releasing PDE5 inhibitors represent a potential therapeutic strategy for chronic non-healing wounds.
- TOP-N53's development addresses the critical need for effective treatments for conditions like diabetic foot ulcers.
- The modulation of intracellular signaling via PDE5 inhibition offers a promising avenue for promoting wound closure and tissue regeneration.
