Skin whitening agent targets MC-1 receptor

This property enables melanin to release more than 99% of the absorbed UVR as heat. This photo-protection prevents the DNA damage that is responsible for malignant melanoma and various skin cancers. However, despite many advantages, people generally consider pigmentation undesirable. Therefore, there is strong need for an agent that inhibits melanin production thereby providing brighter skin tone, while preserving all other protective properties that melanin provides. To meet this need, Miwon has developed and patented a new skin whitening agent, methyl undecenoyl leucinate (Fig. 1), an active ingredient of DermaPep UL. Methyl undecenoyl leucinate provides even pigmentation against age spots (melasma) as well as general skinwhitening activity. Methyl undecenoyl leucinate interacts with MC1R, a receptor for -MSH, competes against its natural ligand, -MSH, and thereby prevents any further activation of melanogenic genes such as tyrosinase, TRP1, TRP2 (DCT), MITF and POMC and finally blocks melanin synthesis.

Mechanism of whitening action

 Melanin, the end-product of complex multistep transformations of L-tyrosine, is the major factor of skin and hair-darkening and provides protection from damage by UVR. The melanocortin 1 receptor (MC1R), encodes seven-transmembrane G-protein coupled receptors, is expressed predominantly by melanocytes and is a key protein that regulates melanin synthesis. The stimulation of the MC1R is upregulated by a-melanocyte stimulating hormone (-MSH) and down-regulated by agouti signal protein (ASP/ASIP). -melanocyte stimulating hormone (-MSH) is a tridecapeptide derived from the proopiomelanocortin (POMC) by posttranslational processing. This molecule serves as the source for several peptide hormones such as adrenocorticotrophin (ACTH), -MSH, -MSH and -MSH, and the endogenous opioids including -endorphin. C- and N-terminal fragments of -MSH have significant melanotropic effects. -MSH/MC1R signalling mechanism is involved in the control of tyrosinase activity, melanin synthesis and melanosome transfer. -MSH-bound MC1R activates adenylyl cyclase (AC), inducing cyclic AMP productions. This cascade involves the activation of protein kinase A (PKA) and cAMP responsive-elementbinding protein (CREB) transcription factor, leading to transcriptionally activate various genes including those encoding microphthalmia associated transcription factor (MITF), the melanocyte-specific transcription factor crucial for expression of numerous melanogenic enzymes and melanocyte development/differentiation factors such as tyrosinase, TRP1, and TRP2 (DCT) which result in an elevated melanin synthesis (Fig. 2). In vitro and in vivo study results showed that methyl undecenoyl leucinate is far more effective than other known whitening ingredients such as kojic acid and arbutin. In addition to its effect on melanocytes, methyl undecenoyl leucinate provided strong anti-inflammatory activity against harmful UV on human keratinocytes.