Hair Loss

AHK-Cu is a synthetic copper peptide composed of three amino acids (alanine, histidine, and lysine) complexed with copper ions. Research demonstrates that AHK-Cu stimulates hair follicle growth by promoting dermal papilla cell proliferation and preventing apoptosis at concentrations of 10⁻¹² to 10⁻⁹ M. The peptide enhances VEGF production while reducing TGF-β1 secretion, supporting angiogenesis and tissue regeneration. Beyond hair growth, copper peptides show significant benefits for skin regeneration, wound healing, and anti-aging through enhanced collagen and elastin synthesis.

RU-58841 (also known as PSK-3841 or HMR-3841) is a nonsteroidal anti-androgen compound originally developed by Roussel Uclaf in the 1980s for topical treatment of androgen-dependent conditions. The compound functions as a competitive androgen receptor antagonist with high affinity for androgen receptors in hair follicles and sebaceous glands. RU-58841 demonstrates a relative binding affinity of 5% compared to DHT and exhibits a notably short in vivo half-life of less than one hour, making it unsuitable for systemic use but ideal for topical application. The mechanism involves blocking dihydrotestosterone (DHT) from binding to androgen receptors in dermal papilla cells, thereby preventing follicular miniaturization characteristic of androgenetic alopecia. Preclinical studies in animal models demonstrated potent efficacy, with 60% reduction in sebaceous gland size in hamsters and significant hair regrowth in stumptailed macaques without systemic antiandrogenic effects. Human clinical trials conducted by ProStrakan (Phase I with 30 subjects and Phase IIa with 120 subjects) reportedly showed equivalent or better hair growth compared to finasteride after six months of treatment with 2.5% or 5% topical solutions applied once daily. However, these clinical trial results were never formally published in peer-reviewed journals, and development was discontinued following corporate acquisition. RU-58841 is not FDA-approved and no regulatory agency has authorized its use in humans. Despite lack of approval, the compound is available through research chemical suppliers and is used off-label by individuals seeking alternatives to approved treatments like finasteride and minoxidil.

Pyrilutamide (also known as KX-826) is a novel, nonsteroidal, selective androgen receptor (AR) antagonist being developed as a topical treatment for androgenetic alopecia (male and female pattern hair loss). The compound functions as a high-affinity silent antagonist that competitively binds to androgen receptors in dermal papilla cells and hair follicles, preventing dihydrotestosterone (DHT) from activating these receptors and subsequently blocking the cascade of events that lead to hair follicle miniaturization. Mechanistically, pyrilutamide decreases androgen receptor protein levels and enhances Wnt/β-catenin signaling pathways crucial for hair growth, while also preventing the androgen-mediated secretion of paracrine inhibitory factors such as TGF-β1, IL-6, and DKK-1 that suppress hair follicle epithelial cell proliferation and induce apoptosis. Clinical development has progressed through multiple Phase II and Phase III trials in both China and the United States for male and female androgenetic alopecia. Phase II trials demonstrated promising results with the 0.5% solution applied twice daily showing increases in target area hair count (TAHC) of 10 hairs/cm² in U.S. males and 22.73 hairs/cm² in Chinese males after 24 weeks, with females showing an 11.39 hairs/cm² increase compared to placebo. However, the pivotal Phase III efficacy trial announced in November 2023 failed to meet its primary endpoint, showing no statistically significant difference in TAHC compared to placebo at 24 weeks, though the treatment did demonstrate significant increases in non-vellus TAHC compared to baseline and maintained an excellent safety profile. A separate long-term safety Phase III trial completed with more encouraging results, reporting that 53% of men and 48% of women experienced hair improvement after 52 weeks of twice-daily application of 0.5% pyrilutamide solution. Throughout all clinical trials, pyrilutamide has demonstrated a favorable safety profile with no serious adverse events (SAE) or adverse drug reactions (ADR) reported. Pyrilutamide is not currently FDA-approved and remains investigational, though it is available through research chemical suppliers for experimental use. The compound represents a new generation of topical antiandrogens designed to provide localized efficacy without the systemic side effects associated with oral antiandrogen therapies like finasteride.