PTD-DBM

Also known as: CXXC5-Dvl competing peptide, PTD-DBM-FITC

Evidence: Preclinical

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Overview

Cell-permeable peptide that blocks the CXXC5-Dishevelled interaction to de-repress Wnt/beta-catenin signaling; studied topically in mice for hair regrowth and wound healing.

PTD-DBM fuses a protein transduction domain to the Dishevelled-binding motif of CXXC5, a negative regulator of Wnt signaling. By competing CXXC5 away from Dishevelled it restores Wnt/beta-catenin activity in hair follicles. Mouse studies (notably with valproic acid co-treatment) report new hair follicle neogenesis and accelerated wound healing. There is no human trial data.

Benefits

Hair regrowth and wound-induced hair neogenesis (mouse), faster cutaneous wound healing (mouse), studied in a DHT-induced androgenetic alopecia model (mouse)

Dosing reference

Research dose: Variable

Studied only as a topical solution in mice. The developers' papers use concentrations 100-fold apart: 100 microM in wound studies (Lee 2015) and 10 mM in an androgenetic alopecia model (Ryu 2023). The hair regrowth study combined it with valproic acid (Lee 2017). No human dose, trial or safety data.

Mechanism

A polyarginine protein transduction domain (eight arginines) joined by a four-glycine linker to the Dishevelled-binding motif of CXXC5 (residues 284 to 296). CXXC5 binds Dishevelled and negatively regulates Wnt/beta-catenin signalling in skin wound healing (Lee 2015). The peptide competes with CXXC5 for Dishevelled, which in mouse skin restored Wnt/beta-catenin activity, hair regrowth and wound-induced hair neogenesis (Lee 2017; Kim and Garza 2017). CXXC5 also mediates DHT-induced hair loss through prostaglandin D2 in mice (Ryu 2023). The developers later moved to small-molecule CXXC5 inhibitors such as KY19382 (Ryu 2021). DBM means Dishevelled-binding motif, not a DOPA-binding motif.

Evidence

Preclinical: animal or in vitro data only

Topical PTD-DBM at 100 microM accelerated cutaneous wound healing in mice; CXXC5 acts as a negative regulator of healing (Lee et al., 2015)
With valproic acid, topical PTD-DBM stimulated hair regrowth and wound-induced hair neogenesis in mice (Lee et al., 2017)
Topical PTD-DBM at 10 mM was used in a mouse model of DHT-induced androgenetic alopecia (Ryu et al., 2023)
Delivered from an adhesive hydrogel patch as part of a combination drug therapy for regenerative wound healing in mice (Lee et al., 2023)
Human-trial status: none. All studies are in mice from one Yonsei University group with a commercial interest; the group's successors are small molecules such as KY19382 (Ryu et al., 2021)

References

Side effects

No safety study in any species; the mouse studies were not designed to detect harm. The effect of sustained Wnt/beta-catenin activation on cell proliferation has not been characterized. No human data.

Storage

Storage: Refrigerated (2-8°C)
Lyophilized: 24+ months at room temperature

Pharmacology

Half-life: No published pharmacokinetic data in any species
Bioavailability: Not measured. Applied topically to mouse skin; the polyarginine domain is there for cell entry (Lee 2017)
Molecular weight: 3210.86 Da
Sequence: RRRRRRRRGGGGRKTGHQICKFRKCK