Abstract
Background:
Tyrosinase is the rate-limiting enzyme in melanin biosynthesis, and its overactivity contributes to hyperpigmentation disorders. Existing tyrosinase inhibitors are often limited by poor potency against human tyrosinase (hTYR) or safety concerns.
Aims:
To evaluate the inhibitory potency, safety, and multifunctional activity of KT-939, a newly synthesized human tyrosinase inhibitor, compared with established depigmenting agents.
Patients/methods:
KT-939 was synthesized and tested in vitro for tyrosinase inhibition, melanin suppression in human melanocytes, antioxidant activity (DPPH radical scavenging, NRF2 pathway activation), and anti-inflammatory activity (cytokine expression in LPS-stimulated macrophages). Safety was assessed in multiple skin-related cell lines. A 28-day, single-center clinical study in healthy women with sensitive skin assessed the effects of 0.2% KT-939 lotion on pigmentation and tolerability.
Results:
KT-939 strongly inhibited hTYR (IC₅&sub0; = 0.07 μM), demonstrating ~4-fold greater potency than Thiamidol and far surpassing other comparators. In melanocytes, KT-939 reduced melanin production (IC₅&sub0; = 0.36 μM) with reversible effects upon withdrawal. KT-939 also displayed antioxidant activity, NRF2 activation, and suppression of pro-inflammatory cytokines, without cytotoxicity up to 50 μM. Clinically, 28 days of KT-939 lotion use improved skin spot lightening, tone uniformity, and overall brightness, with good tolerability in sensitive skin.
Conclusions:
KT-939 is a potent and safe human tyrosinase inhibitor with additional antioxidant and anti-inflammatory activity. These findings support its potential in cosmetic skin brightening and as a therapeutic candidate for hyperpigmentation disorders.
Keywords:
KT‐939; hyperpigmentation; melanogenesis; tyrosinase.