Development of Pigmentation-Regulating Agents by Drug Repositioning

Abstract

Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning.

Study of botulinum toxin type A for the treatment of ultraviolet B‐induced hyperpigmentation: A prospective, randomized, controlled trial

“…α‐MSH binds to melanocortin 1 receptor (MC1R) on melanocytes, which further activates cascade responses of melanin production 1,3 . In addition, UV irradiation also increases the accumulation of melanin in keratinocyte by promoting the melanosome transfer from melanocytes to keratinocyte, mediated through intracellular Ca 2 + accumulation and E‐cadherin 3 . Other melanogenic factors induced by UV irradiation include endothelin‐1, interleukin‐1, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), SCF, and NGF 3 .…”

“…Another study conducted on mouse skin also reported consistent results. The backs of the mice were exposed to UVB with a total energy of 0.5 J/cm 2 . One week before the first UVB irradiation and after the seventh UVB irradiation, BTX‐A was intradermally injected into the mouse skin at a dose of 30 units per kg (approximately 1 unit per 1 cm 2 ).…”

“…The energy required for hyperpigmentation induction was determined based on the participants’ FPT skin types. Participants with FPT skin types III and IV were irradiated with 270 and 300 mj/cm, 2 respectively. All participants were instructed to avoid sun exposure, use of any topical agents, and vigorous rubbing on the experimental sites throughout the study period.…”

Incobotulinum Toxin Type A for Treatment of Ultraviolet-B-Induced Hyperpigmentation: A Prospective, Randomized, Controlled Trial

“…Upon exposure to UV radiation, keratinocytes are stimulated to secrete α-MSH, which enhances melanogenesis through multiple pathways related to cAMP, protein kinase A (PKA), cAMP response element-binding protein (CREB), and microphthalmia-associated transcription factor (MITF) activity [6,7]. Several skin-lightening procedures have focused on strategies that inhibit these signals [8].…”

GIF-2209, an Oxindole Derivative, Accelerates Melanogenesis and Melanosome Secretion via the Modification of Lysosomes in B16F10 Mouse Melanoma Cells

“…A number of small compounds that modulate melanogenesis have been reported and are categorized into several groups based on the mechanism of action, cellular signaling [ 4 , 5 ], transcription [ 6 ], translation [ 7 ], cellular trafficking [ 8 ], and degradation [ 9 ]. Post-translational modulators of melanogenic factors are often associated with intracellular trafficking and affect the maturation and fate of melanosomes and related organelles [ 10 ].…”